High BMP4 expression in low/intermediate risk BCP-ALL identifies children with poor outcomes.

Pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) outcome has improved in the last decades, but leukemic relapses are still one of the main problems of this disease. Bone morphogenetic protein 4 (BMP4) was investigated as a new candidate biomarker with potential prognostic relevance, and its pathogenic role was assessed in the development of disease. A retrospective study was performed with 115 pediatric patients with BCP-ALL, and BMP4 expression was analyzed by quantitative reverse transcription polymerase chain reaction in leukemic blasts at the time of diagnosis. BMP4 mRNA expression levels in the third (upper) quartile were associated with a higher cumulative incidence of relapse as well as a worse 5-year event-free survival and central nervous system (CNS) involvement. Importantly, this association was also evident among children classified as having a nonhigh risk of relapse. A validation cohort of 236 patients with BCP-ALL supported these data. Furthermore, high BMP4 expression promoted engraftment and rapid disease progression in an NSG mouse xenograft model with CNS involvement. Pharmacological blockade of the canonical BMP signaling pathway significantly decreased CNS infiltration and consistently resulted in amelioration of clinical parameters, including neurological score. Mechanistically, BMP4 favored chemoresistance, enhanced adhesion and migration through brain vascular endothelial cells, and promoted a proinflammatory microenvironment and CNS angiogenesis. These data provide evidence that BMP4 expression levels in leukemic cells could be a useful biomarker to identify children with poor outcomes in the low-/intermediate-risk groups of BCP-ALL and that BMP4 could be a new therapeutic target to blockade leukemic CNS disease.

Spatio-temporal trends of mercury levels in alluvial gold mining spoils areas monitored between rainy and dry seasons in the Peruvian Amazon.

Artisanal and small-scale gold mining (ASGM) in the Amazon has degraded tropical forests and escalated mercury (Hg) pollution, affecting biodiversity, ecological processes and rural livelihoods. In the Peruvian Amazon, ASGM annually releases some 181 tons of Hg into the environment. Despite some recent advances in understanding the spatial distribution of Hg within gold mine spoils and the surrounding landscape, temporal dynamics in Hg movement are not well understood. We aimed to reveal spatio-temporal trends of soil Hg in areas degraded by ASGM.,. We analyzed soil and sediment samples during the dry and rainy seasons across 14 ha of potentially contaminated sites and natural forests, in the vicinities of the Native community of San Jacinto in Madre de Dios, Peru. Soil Hg levels of areas impacted by ASGM (0.02 ± 0.02 mg kg-1) were generally below soil environmental quality standards (6.60 mg kg-1). However, they showed high variability, mainly explained by the type of natural cover vegetation, soil organic matter (SOM), clay and sand particles. Temporal trends in Hg levels in soils between seasons differed between landscape units distinguished in the mine spoils. During the rainy season, Hg levels decreased up to 45.5% in uncovered soils, while in artificial pond sediments Hg increased by up to 961%. During the dry season, uncovered degraded soils were more prone to lose Hg than sites covered by vegetation, mainly due to higher soil temperatures and concomitantly increasing volatilization. Soils from natural forests and degraded soil covered by regenerating vegetation showed a high capacity to retain Hg mainly due to the higher plant biomass, higher SOM, and increasing concentrations of clay particles. Disturbingly, our findings suggest high Hg mobility from gold mine spoil to close by sedimentary materials, mainly in artificial ponds through alluvial deposition and pluvial lixiviation. Thus, further research is needed on monitoring, and remediation of sediments in artificial to design sustainable land use strategies.

Analyzing the Clinical Potential of Stromal Vascular Fraction: A Comprehensive Literature Review.

Background: Regenerative medicine is evolving with discoveries like the stromal vascular fraction (SVF), a diverse cell group from adipose tissue with therapeutic promise. Originating from fat cell metabolism studies in the 1960s, SVF's versatility was recognized after demonstrating multipotency. Comprising of cells like pericytes, smooth muscle cells, and, notably, adipose-derived stem cells (ADSCs), SVF offers tissue regeneration and repair through the differentiation and secretion of growth factors. Its therapeutic efficacy is due to these cells' synergistic action, prompting extensive research. Methods: This review analyzed the relevant literature on SVF, covering its composition, action mechanisms, clinical applications, and future directions. An extensive literature search from January 2018 to June 2023 was conducted across databases like PubMed, Embase, etc., using specific keywords. Results: The systematic literature search yielded a total of 473 articles. Sixteen articles met the inclusion criteria and were included in the review. This rigorous methodology provides a framework for a thorough and systematic analysis of the existing literature on SVF, offering robust insights into the potential of this important cell population in regenerative medicine. Conclusions: Our review reveals the potential of SVF, a heterogeneous cell mixture, as a powerful tool in regenerative medicine. SVF has demonstrated therapeutic efficacy and safety across disciplines, improving pain, tissue regeneration, graft survival, and wound healing while exhibiting immunomodulatory and anti-inflammatory properties.

Sex differences and sex steroids influence on the presentation and severity of cardiovascular autonomic neuropathy of patients with type 1 diabetes.

BACKGROUND: Sex differences characterize cardiovascular outcomes in patients with type 1 diabetes. Cardioautonomic neuropathy is a common complication of type 1 diabetes that associates increased morbi-mortality. Data regarding the interplay between sex and cardiovascular autonomic neuropathy are scarce and controversial in these patients. We aimed to address sex-related differences in the prevalence of seemingly asymptomatic cardioautonomic neuropathy in type 1 diabetes, and their associations with sex steroids. METHODS: We conducted a cross-sectional study including 322 consecutively recruited patients with type 1 diabetes. Cardioautonomic neuropathy was diagnosed using Ewing's score and power spectral heart rate data. We assessed sex hormones by liquid chromatography/tandem mass spectrometry. RESULTS: When considering all subjects as a whole, asymptomatic cardioautonomic neuropathy prevalence was not significantly different between women and men. When age was taken into account, the prevalence of cardioautonomic neuropathy was similar among young men and those > 50 years. However, in women > 50 years, the prevalence of cardioautonomic neuropathy doubled that of young women [45.8% (32.6; 59.7) vs. 20.4% (13.7; 29.2), respectively]. The OR of having cardioautonomic neuropathy was 3.3 higher in women > 50 years than in their younger counterparts. Furthermore, women presented more severe cardioautonomic neuropathy than men. These differences were even more marked when women were classified according their menopausal status instead of age. Peri- and menopausal women had an OR 3.5 (1.7; 7.2) of having CAN compared with their reproductive-aged counterparts [CAN prevalence: 51% (37; 65) vs. 23% (16; 32), respectively]. A binary logistic regression model (R2: 0.161; P = 0.001) displayed age > 50 years as a significant determinant of cardioautonomic neuropathy only in women. Androgens were positively associated with heart rate variability in men, and negatively in women. Accordingly, cardioautonomic neuropathy was associated with increased testosterone/estradiol ratio in women but to decreased testosterone concentrations in men. CONCLUSIONS: Menopause in women with type 1 diabetes is accompanied by an increase in the prevalence of asymptomatic cardioautonomic neuropathy. This age-related excess risk of cardioautonomic neuropathy is not observed in men. Men and women with type 1 diabetes have opposite associations between circulating androgens and indexes of cardioautonomic function. Trial registration ClinicalTrials.gov Identifier: NCT04950634.

NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration.

BACKGROUND: Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. RESULTS: Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. CONCLUSIONS: These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.

Revision surgery following long lumbopelvic constructs for adult spinal deformity: prospective experience from two dedicated databases.

PURPOSE: Pan Lumbar Arthodesis (PLA) are often required for Adult Spinal Deformity (ASD) correction, reducing significantly the compensatory capacity in case of postoperative sagittal malalignment. Few papers have investigated outcomes and complications in this vulnerable subset of patients. The objective of this study was to assess revision surgery rate for PLA in ASD, its risk factors and impact on clinical outcomes. METHODS: Retrospective multicenter review of prospective ASD data from 7 hospitals covering Europe and Asia. ASD patients included in two prospective databases having a posterior instrumentation spanning the whole lumbar region with more than 2-years of follow-up were reviewed. Demographic, surgical, radiographic parameters and Health-Related Quality of Life (HRQoL) scores were analyzed. Univariate and multivariate regression models analyzed risk factors for revision surgery as well as surgical outcomes. Patients with Early versus Late and PJK versus Non-PJK mechanical complications were also compared. RESULTS: Out of 1359 ASD patients included in the database 589 (43%) had a PLA and 357 reached 2-years mark. They were analyzed and compared to non-PLA patients. Average age was 67 and 82% were females. 100 Patients (28.1%) needed 114 revision surgeries (75.4% for mechanical failures). Revised patients were more likely to have a nerve system disorder, higher BMI and worst immediate postoperative alignment (as measured by GAP Parameters). These risk factors were also associated with earlier mechanical complications and PJK. Deformity and HRQoL parameters were comparable at baseline. Non-revised patients had significantly better clinical outcomes at 2-years (SRS 22 scores, ODI, Back pain). Multivariate analysis could identify nerve system disorder (OR 4.8; CI 1.8-12.6; p = 0.001), postoperative sagittal alignment (GAP Score) and high BMI (OR 1.07; CI 1.01-1.13; p = 0.004) as independent risk factors for revisions. CONCLUSIONS: Revision surgery due to mechanical failures is relatively common after PLA leading to worse clinical outcomes. Prevention strategies should focus on individualized restoration of sagittal alignment and better weight control to decrease stress on these rigid constructs in non-compliant spines. Nerve system disorders independently increase revision risk in PLA. LEVEL OF EVIDENCE II: Prognosis.

Effect of Different Substitutions at the 1,7-Bay Positions of Perylenediimide Dyes on Their Optical and Laser Properties.

Perylenediimide (PDI) compounds are widely used as the active units of thin-film organic lasers. Lately, PDIs bearing two sterically hindering diphenylphenoxy groups at the 1,7-bay positions have received attention because they provide a way to red-shift the emission with respect to bay-unsubstituted PDIs, while maintaining a good amplified spontaneous emission (ASE) performance at high doping rates. Here, we report the synthesis of a series of six PDI derivatives with different aryloxy groups (PDI 6 to PDI 10) or ethoxy groups (PDI 11) at the 1,7 positions of the PDI core, together with a complete characterization of their optical properties, including absorption, photoluminescence, and ASE. We aim to stablish structure-property relationships that help designing compounds with optimized ASE performance. Film experiments were accomplished at low PDI concentrations in the film, to resemble the isolated molecule behaviour, and at a range of increasing doping rates, to investigate concentration quenching effects. Compounds PDI 10 and PDI 7, bearing substituents in the 2' positions of the benzene ring (the one contiguous to the linking oxygen atom) attached to the 1,7 positions of the PDI core, have shown a better threshold performance, which is attributed to conformational (steric) effects. Films containing PDI 11 show dual ASE.

Stromal Vascular Fraction Therapy for Knee Osteoarthritis: A Systematic Review.

Background and Objectives: Knee osteoarthritis (OA) is a widespread joint disease, set to increase due to aging and rising obesity. Beyond cartilage degeneration, OA involves the entire joint, including the synovial fluid, bones, and surrounding muscles. Existing treatments, such as NSAIDs and corticosteroid injections, mainly alleviate symptoms but can have complications. Joint replacement surgeries are definitive but carry surgical risks and are not suitable for all. Stromal vascular fraction (SVF) therapy is a regenerative approach using cells from a patient's adipose tissue. SVF addresses as degenerative and inflammatory aspects, with potential for cartilage formation and tissue regeneration. Unlike traditional treatments, SVF may reverse OA changes. Being autologous, it reduces immunogenic risks. Materials and Methods: A systematic search was undertaken across PubMed, Medline, and Scopus for relevant studies published from 2017 to 2023. Keywords included "SVF", "Knee Osteoarthritis", and "Regenerative Medicine". Results: This systematic search yielded a total of 172 articles. After the removal of duplicates and an initial title and abstract screening, 94 full-text articles were assessed for eligibility. Of these, 22 studies met the inclusion criteria and were subsequently included in this review. Conclusions: This review of SVF therapy for knee OA suggests its potential therapeutic benefits. Most studies confirmed its safety and efficacy, and showed improved clinical outcomes and minimal adverse events. However, differences in study designs and sizes require a careful interpretation of the results. While evidence supports SVF's positive effects, understanding methodological limitations is key. Incorporating SVF is promising, but the approach should prioritize patient safety and rigorous research.

Transcultural Pilot Study of the Efficacy of Reminiscence Therapy for Mexican and Spanish Older Adults with Different Levels of Cognitive Decline.

The main objective for this study is to analyze the impact of a positive reminiscence therapy program (REMPOS) in cognitive functioning and depressive symptomatology for older adults in different vital situations (healthy aging, mild cognitive impairment, and Alzheimer's disease).This is a transcultural comparative study (older people from Spain and Mexico). A randomized design with pre-posttest measurement and twelve groups was formulated, during a period of six months of intervention (3 in Mexico and 3 in Spain). The design had: 6 experimental groups with REMPOS intervention (3 in Mexico and 3 in Spain) during a period of six months and 6 control groups that received cognitive stimulation.While a key aspect of this study is the cross-cultural differences, an important part is to determine whether each experimental group had similar results in terms of the change in magnitude between the pre and post analysis. In general, intervention significantly improved cognitive function and decreased depressive symptoms.These findings provide further evidence about the efficacy of the REMPOS therapy between different types of aging and both geographical and cultural contexts (Spain and Mexico).

Kinesin-14 family proteins and microtubule dynamics define S. pombe mitotic and meiotic spindle assembly, and elongation.

To segregate the chromosomes faithfully during cell division, cells assemble a spindle that captures the kinetochores and pulls them towards opposite poles. Proper spindle function requires correct interplay between microtubule motors and non-motor proteins. Defects in spindle assembly or changes in spindle dynamics are associated with diseases, such as cancer or developmental disorders. Here, we compared mitotic and meiotic spindles in fission yeast. We show that, even though mitotic and meiotic spindles underwent the typical three phases of spindle elongation, they have distinct features. We found that the relative concentration of the kinesin-14 family protein Pkl1 is decreased in meiosis I compared to mitosis, while the concentration of the kinesin-5 family protein Cut7 remains constant. We identified the second kinesin-14 family protein Klp2 and microtubule dynamics as factors necessary for proper meiotic spindle assembly. This work defines the differences between mitotic and meiotic spindles in fission yeast Schizosaccharomyces pombe, and provides prospect for future comparative studies.This article has an associated First Person interview with the first author of the paper.

Green and wide acceptance angle solar concentrators.

A low-toxicity photopolymer was employed to prepare holographic solar concentrators (HSCs). The main aim of this study is to obtain a versatile holographic element to concentrate the sunlight from different relative positions of the Sun during the day, avoiding the need of expensive tracking systems. Multiplexed holographic elements that combine symmetric and asymmetric holographic lenses of low frequency (545 l/mm) have been recorded in the same plate to concentrate the sunlight from sunrise to sunset. The holographic behavior of HSCs has been studied by measuring the angular diffraction efficiency at 633 nm (close to the maximum response of silicon cells). The efficiency of the complete system "HSC-solar cell" has been evaluated by measuring the short-circuit current (Isc) under solar illumination at different incident angles. This study overcomes the trade-off between good efficiency and high incident acceptance angle, showing an important breakthrough to obtain wide acceptance angle systems.

Is routine blood typing and screening necessary for degenerative cervical spine surgery patients in specialty surgical hospitals?

BACKGROUND: Blood loss warranting transfusion is a relatively rare requirement for degenerative cervical spine surgery. Despite this rarity, pretransfusion testing (blood typing, screening, and cross-matching) has become routine in most parts of the world. We sought to determine if such routine testing is necessary for patients who undergo degenerative cervical spine surgery patients in specialty surgical hospitals by (1) measuring the current rate of intraoperative transfusions in degenerative cervical spine surgery and (2) identifying risk factors for transfusions. STUDY METHODS: Retrospective review was performed on patients who underwent degenerative cervical spine surgery in two institutions. Demographic and baseline clinical and laboratory data were collected and analyzed to identify predictors of transfusion. Bivariate and multivariate logistic regression analysis was performed to identify perioperative transfusion risk factors. RESULTS: Overall transfusion rate was 1.9% (7/372), with no emergent transfusions. Decreases between preoperative and postoperative hemoglobin and hematocrit were 1.4 (SD 1.1) g/dL and 7.2 (SD 4.1) %, respectively. Multivariate logistic regression identified preoperative Hgb lower than 12 gr/dl (OR 27.62; 95% CI 4.31-176.96; p < 0.001) as significant independent transfusion risk factor. The receiver operating characteristic (ROC) curve for the model showed a very good discriminatory power with an area under the curve of 0.91. DISCUSSION: Our study suggests that pretransfusion testing for all patients undergoing degenerative cervical spine surgery is unnecessary. We recommend that only patients with preoperative Hgb lower than 12 gr/dl would routinely need pretransfusion testing.

Extracorporeal photopheresis in paediatric patients: A retrospective comparison between different 'off-line' protocols.

BACKGROUND AND OBJECTIVES: Extracorporeal photopheresis (ECP) has been shown to be an effective treatment for graft-versus-host disease (GvHD). However, information regarding lymphocyte collection for ECP in children is limited. The aim of this study was to analyse and compare lymphocyte collection for ECP in children using different devices and protocols. Moreover, we have studied both safety and variables of the infused product related to treatment efficacy. PATIENTS AND METHODS: This was a retrospective study of 91 patients who underwent 1524 apheresis procedures with either the COBE Spectra or Spectra Optia system. The comparison study between the Optia protocols (MNC and CMNC) was prioritized. We analysed 578 procedures using the Optia blood cell separator: 204 and 374 using the MNC and the CMNC protocol, respectively. RESULTS: The Optia CMNC protocol showed better collection efficiency, with increased lymphocyte collection per kg of body weight (p < 0.001). On multivariate analysis, the type of protocol showed no relationship with haematocrit or platelet loss. Most procedures were well-tolerated, with the most frequent adverse events related to venous access (21.7%). Seventy-one percent of patients had either partial or complete clinical GvHD response. In the multivariate model, only two variables were associated with a better response to ECP, younger age and a greater increase of B lymphocytes after treatment. CONCLUSION: Lymphocyte collection for ECP is well-tolerated in most children, achieving complete or partial response in more than half of GvHD patients. CMNC is the optimal software to perform lymphocyte collection in children.

Mobilization with high-dose granulocyte colony-stimulating factor alone at 12 µg/kg twice a day in high-risk pediatric patients: A retrospective analysis of the experience in a single center.

INTRODUCTION: Mobilization regimes in pediatric patients at high risk for poor mobilization are not standardized across different institutions. We present a retrospective analysis of our experience with a high-dose granulocyte colony-stimulating factor (G-CSF) regime of 12 µg/Kg per body weight (BW) twice a day for 4 days used in high-risk patients. MATERIAL AND METHODS: We report the results of all pediatric patients mobilized with high-dose G-CSF between January 1999 and February 2021 in our center. A successful mobilization was defined as a peripheral blood (PB) CD34+ cell count of ≥10 CD34+ cells/µl on the fifth day of mobilization immediately before leukapheresis. A minimum cell yield of ≥2 × 106 CD34+ cells/Kg of BW was required for a successful collection. RESULTS: Of the 262 patients included in the analysis, mobilization failure was found in 27 (10.3%). In a univariate analysis, this was associated with age, weight, baseline diagnosis, and having undergone a previous mobilization cycle, the latter being the only factor that remained significantly associated in a multivariate analysis (P = 0.03). The 54 patients (20.6%) did not reach the minimum required CD34+ cell yield. 50.4% of the patients reported adverse events (AEs) during the mobilization period, and 23 (9.1%) reported 3 or more concomitant AEs. However, all of them were mild and did not affect the mobilization schedule. CONCLUSIONS: Although most high-risk pediatric patients are successfully mobilized with the high-dose G-CSF regime, this approach does not salvage all of them and significantly increases the presence of AEs in comparison to standard-dose regimes.

Combined anterior-posterior versus all-posterior approaches for adult spinal deformity correction: a matched control study.

PURPOSE: Anterior approaches are gaining popularity for adult spinal deformity (ASD) surgeries especially with the introduction of hyperlordotic cages and improvement in MIS techniques. Combined Approaches provide powerful segmental sagittal correction potential and increase the surface area available for fusion in ASD surgery, both of which would improve overall. This is the first study directly comparing surgical outcomes between combined anterior-posterior approaches and all-posterior approach in a matched ASD population. METHODS: This is a retrospective matched control cohort analysis with substitution using a multicenter prospectively collected ASD data of patients with > 2 year FU. Matching criteria include: age, American Society of Anesthesiologists Score, Lumbar Cobb angle, sagittal deformity (Global tilt) and ODI. RESULTS: In total, 1024 ASD patients were available for analysis. 29 Combined Approaches patients met inclusion criteria, and only 22 could be matched (1:2 ratio). Preoperative non-matched demographical, clinical, surgical and radiological parameters were comparable between both groups. Combined approaches had longer surgeries (548 mns vs 283) with more blood loss (2850 ml vs 1471) and needed longer ICU stays (74 h vs 27). Despite added morbidity, they had comparable complication rates but with significantly less readmissions (9.1% vs 38.1%) and reoperations (18.2% vs 43.2%) at 2 years. Combined Approaches achieved more individualised and harmonious deformity correction initially. At the 2 years control, Combined Approaches patients reported better outcomes as measured by COMI and SRS scores. This trend was maintained at 3 years. CONCLUSION: Despite an increased initial surgical invasiveness, combined approaches seem to achieve more harmonious correction with superior sagittal deformity control; they need fewer revisions and have improved long-term functional outcomes when compared to all-posterior approaches for ASD deformity correction.

Community-engaged asset mapping with Latinx immigrant families of youth with disabilities.

Asset mapping is a participatory methodology that engages community members in identifying services and settings that promote health and well-being. This study aimed to identify community assets from the perspective of Latinx immigrant families with youth with disabilities. Latinx immigrant families (n = 21) participated in the mapping, followed by a reflection session and an open forum (n = 30). The findings revealed that families identified faith-based organizations and social service agencies as some of the main assets in their communities, while they identified mental health services as the most needed. The results also showed that participants preferred to utilize services and resources that are within walking distance of their homes, provide safe spaces, treat them well, offer bilingual services, do not require documentation, and are affordable. This study has important implications for community scholars and practitioners interested in implementing asset-based methodologies that focus on participants as experts of their own realities and agents of change and that promote advocacy and empowerment actions.

Promoting justice through community-based research: International case studies.

Community-based participatory research (CBPR) approaches to promoting justice focus on working from the ground up and giving a voice to marginalized communities regarding their concerns, potential solutions, and how to address social justice issues that matter to them. The pursuit of justice is often related to efforts to attain personal as well as collective well-being. In this paper, we illustrate three exemplars of community psychologists' efforts to promote justice. Within each case study, we discuss the social and community context and examine how the researchers built partnerships and solidarity, developed ways of doing, and approached challenges and solutions. First, we present an example to promote economic justice through an entrepreneurship initiative developed in collaboration with young Black youth with disabilities in the United States. The second case illustrates an effort to promote reproductive justice in collaboration with Roma women and girls in Spain. The third exemplar depicts the use of life stories as a method to raise the voices of displaced, marginalized indigenous women in Peru. Based on these three case studies, we present a synthesis model of social justice. We also discuss implications for future studies emphasizing the importance of engaging community participants in research meaningful ways, developing sustainable partnerships, and decolonizing research.

Basal cisternostomy for traumatic brain injury: A case report of unexpected good recovery.

In subarachnoid hemorrhage following traumatic brain injury (TBI), the high intracisternal pressure drives the cerebrospinal fluid into the brain parenchyma, causing cerebral edema. Basal cisternostomy involves opening the basal cisterns to atmospheric pressure and draining cerebrospinal fluid in an attempt to reverse the edema. We describe a case of basal cisternostomy combined with decompressive craniectomy. A 35-year-old man with severe TBI following a road vehicle accident presented with acute subdural hematoma, Glasgow coma scale score of 6, fixed pupils and no corneal response. Opening of the basal cisterns and placement of a temporary cisternal drain led to immediate relaxation of the brain. The patient had a Glasgow coma scale score of 15 on postoperative day 6 and was discharged on day 10. We think basal cisternostomy is a feasible and effective procedure that should be considered in the management of TBI.

Physical exercise effects on metastasis: a systematic review and meta-analysis in animal cancer models.

Physical exercise is considered a well-tolerated adjuvant therapy to mitigate cancer-related side effects, but its impact on metastasis is unclear. The present systematic review and meta-analysis aimed to summarize the evidence on the effects of exercise on metastasis in animal cancer models. A systematic search was conducted to identify controlled studies in animals analyzing the impact of exercise interventions on any marker of metastasis incidence or severity. The pooled mean differences (PMD) were calculated for those endpoints for which a minimum of three studies used the same assessment method. We also calculated the pooled odds ratio (OR) of metastases. Twenty-six articles were included in the systematic review, of which 12 could be meta-analyzed. Exercise training in murine cancer models did not significantly modify the number of metastatic foci (PMD = - 3.18; 95% confidence interval [CI] - 8.32, 1.97; p = 0.23), the weight of metastatic tumors (PMD = - 0.03; 95% CI - 0.10, 0.04; p = 0.41), or the risk of developing metastasis (OR = 0.64; 95% CI 0.10, 4.12; p = 0.64). These findings suggest that exercise has no overall influence on any marker of cancer metastasis incidence or severity in animal models. However, the wide methodological heterogeneity observed between studies might be taken into account and the potential exercise effects on metastasis development remain to be determined in pediatric tumors.

IL-7R is essential for leukemia-initiating cell activity of T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy resulting from the dysregulation of signaling pathways that control intrathymic T-cell development. Relapse rates are still significant, and prognosis is particularly bleak for relapsed patients. Therefore, development of novel therapies specifically targeting pathways controlling leukemia-initiating cell (LIC) activity is mandatory for fighting refractory T-ALL. The interleukin-7 receptor (IL-7R) is a crucial T-cell developmental pathway that is commonly expressed in T-ALL and has been implicated in leukemia progression; however, the significance of IL-7R/IL-7 signaling in T-ALL pathogenesis and its contribution to disease relapse remain unknown. To directly explore whether IL-7R targeting may be therapeutically efficient against T-ALL relapse, we focused on a known Notch1-induced T-ALL model, because a majority of T-ALL patients harbor activating mutations in NOTCH1, which is a transcriptional regulator of IL-7R expression. Using loss-of-function approaches, we show that Il7r-deficient, but not wild-type, mouse hematopoietic progenitors transduced with constitutively active Notch1 failed to generate leukemia upon transplantation into immunodeficient mice, thus providing formal evidence that IL-7R function is essential for Notch1-induced T-cell leukemogenesis. Moreover, we demonstrate that IL-7R expression is an early functional biomarker of T-ALL cells with LIC potential and report that impaired IL-7R signaling hampers engraftment and progression of patient-derived T-ALL xenografts. Notably, we show that IL-7R-dependent LIC activity and leukemia progression can be extended to human B-cell acute lymphoblastic leukemia (B-ALL). These results have important therapeutic implications, highlighting the relevance that targeting normal IL-7R signaling may have in future therapeutic interventions, particularly for preventing T-ALL (and B-ALL) relapse.