Practical uses of the BENCHMARK™ BMX®81 in the road less travelled: Guide catheter comparison for radial access in neurovascular intervention.

BACKGROUND: Radial arterial access has gained interest for neurovascular procedures in recent years. Although there are no randomized control trials for neurointervention procedures using radial access, there is growing literature demonstrating its feasibility and favorable outcomes. Equipment technical improvements, like the recently introduced BENCHMARK™ BMX®81 System, have made radial navigation safer, with improved maneuverability and support for a variety of procedures. We present a multicenter case series highlighting our institutional radial access experience comparing the BMX®81 with alternative catheters. METHODS: Multicenter retrospective cohort study of 80 patients who underwent neurovascular procedures through a radial approach. In half of the cases a BENCHMARK™ BMX®81 System was used. The comparison group consisted of the BENCHMARK™071 and 96, Neuron MAX®088 and BALLAST™ systems. Procedures included endovascular thrombectomy, carotid and brachiocephalic artery stenting, middle meningeal artery embolization, flow diverter stenting, vertebral artery sacrifice, aneurysm coiling, and WEB™ device deployment. RESULTS: In our series, the BMX®81 was successful in the navigation of the anatomy to the target location in 95% of cases. No radial access or BMX®81 related complications were identified. There was no significant difference in fluoroscopy time between the BMX81 and the comparison group. Four patients in the comparison group had catheter-related complications due to vasospasm. Eighty-six percent of BMX®81 cases had satisfactory outcomes and no technical difficulties. The remainder presented technical difficulties, but none of these were considered secondary to the puncture site or support structure. CONCLUSIONS: The BENCHMARK™ BMX®81 System is a recently developed guiding catheter which has design and size features supporting radial access for a variety of neurovascular interventions. Early multicenter experience highlights the ease of use and versatility of this new catheter as an alternative to transfemoral access as well as other catheters used for radial access.

Exploring the role of mindfulness in the stress-recovery balance: 10-Day monitoring of young BMX riders in an intensive training center during a pre-competition cycle.

Considering mindfulness as a multidimensional disposition domain-specific skill and state, this study aimed to explore the effect of the dimensions of mindfulness on the trajectories of biopsychosocial stress-recovery balance and on HRV over 10 days of a pre-competitive cycle. 24 young BMX riders completed mindfulness disposition and domain-specific skill scales. Monitoring of the recovery-stress states was based on biopsychosocial measurements (daily and biweekly). RMSSD was used to assess the organism ability to cope with the training program stimulus. After each training session, riders self-rated their state of mindfulness. Multilevel growth curve analyses examined the linear and/or quadratic trajectories of the athletes' recovery-stress states and the effect of mindfulness on these trajectories. Mindfulness states results showed that the refocusing state had a significant negative quadratic effect over time on daily recovery and sport-specific recovery, and the awareness state on general recovery and total recovery. Concerning the dispositions of mindfulness, the observing component had a significant positive quadratic effect over time on daily stress. Nonreactivity had a significant positive quadratic effect over time on daily recovery and sport-specific recovery, and a significant positive effect on RMSSD. Acting with awareness had a significant positive effect on daily recovery and a significant negative effect on RMSSD. The study offered a better understanding of the effect of mindfulness (dispositions, domain-specific skills, and states) and its different components on the stress-recovery balance. The results suggest that mindfulness could be considered a promising effective psychological recovery strategy.

Single-Cell Profiling Reveals Immune-Based Mechanisms Underlying Tumor Radiosensitization by a Novel Mn Porphyrin Clinical Candidate, MnTnBuOE-2-PyP5+ (BMX-001).

Manganese porphyrins reportedly exhibit synergic effects when combined with irradiation. However, an in-depth understanding of intratumoral heterogeneity and immune pathways, as affected by Mn porphyrins, remains limited. Here, we explored the mechanisms underlying immunomodulation of a clinical candidate, MnTnBuOE-2-PyP5+ (BMX-001, MnBuOE), using single-cell analysis in a murine carcinoma model. Mice bearing 4T1 tumors were divided into four groups: control, MnBuOE, radiotherapy (RT), and combined MnBuOE and radiotherapy (MnBuOE/RT). In epithelial cells, the epithelial-mesenchymal transition, TNF-α signaling via NF-кB, angiogenesis, and hypoxia-related genes were significantly downregulated in the MnBuOE/RT group compared with the RT group. All subtypes of cancer-associated fibroblasts (CAFs) were clearly reduced in MnBuOE and MnBuOE/RT. Inhibitory receptor-ligand interactions, in which epithelial cells and CAFs interacted with CD8+ T cells, were significantly lower in the MnBuOE/RT group than in the RT group. Trajectory analysis showed that dendritic cells maturation-associated markers were increased in MnBuOE/RT. M1 macrophages were significantly increased in the MnBuOE/RT group compared with the RT group, whereas myeloid-derived suppressor cells were decreased. CellChat analysis showed that the number of cell-cell communications was the lowest in the MnBuOE/RT group. Our study is the first to provide evidence for the combined radiotherapy with a novel Mn porphyrin clinical candidate, BMX-001, from the perspective of each cell type within the tumor microenvironment.

BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade.

Aims: Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current investigation aims to evaluate BMX's impact on retinal I/R injury and clarify its implied mechanism of action. Main methods: This study utilized male and female systemic BMX knockout (BMX-/-) mice to conduct experiments. The utilization of Western blot assay and immunofluorescence labeling techniques was employed to investigate variations in the expression of protein and tissue localization. Histomorphological changes were observed through H&E staining and SD-OCT examination. Visual function changes were assessed through electrophysiological experiments. Furthermore, apoptosis in the retina was identified using the TUNEL assay, as well as the ELISA technique, which has been utilized to determine the inflammatory factors level. Key findings: Our investigation results revealed that the knockdown of BMX did not yield a significant effect on mouse retina. In mice, BMX knockdown mitigated the negative impact of I/R injury on retinal tissue structure and visual function. BMX knockdown effectively reduced apoptosis, suppressed inflammatory responses, and decreased inflammatory factors subsequent to I/R injury. The outcomes of the current investigation revealed that BMX knockdown partially protected the retina through downregulating phosphorylation of AKT/ERK/STAT3 pathway. Significance: Our investigation showed that BMX-/- reduces AKT, ERK, and STAT3 phosphorylation, reducing apoptosis and inflammation. Thus, this strategy protected the retina from structural and functional damage after I/R injury.

Intracarotid Infusion of Redox-Active Manganese Porphyrin, MnTnBuOE-2-PyP5+, following Reperfusion Improves Long-Term, 28-Day Post-Stroke Outcomes in Rats.

Endovascular mechanical thrombectomy, combined with a tissue plasminogen activator (t-PA), is efficacious as a standard care for qualifying ischemic stroke patients. However, > 50% of thrombectomy patients still have poor outcomes. Manganese porphyrins, commonly known as mimics of superoxide dismutases, are potent redox-active catalytic compounds that decrease oxidative/nitrosative stress and in turn decrease inflammatory responses, mitigating therefore the secondary injury of the ischemic brain. This study investigates the effect of intracarotid MnTnBuOE-2-PyP5+ (BMX-001) administration on long-term, 28-day post-stroke recovery in a clinically relevant setting. The 90 min of transient middle cerebral artery occlusion was performed in young, aged, male, female, and spontaneous hypertension rats. All physiological parameters, including blood pressure, blood gas, glucose, and temperature, were well controlled during ischemia. Either BMX-001 or a vehicle solution was infused through the carotid artery immediately after the removal of filament, mimicking endovascular thrombectomy, and was followed by 7 days of subcutaneous injection. Neurologic deficits and infarct volume were assessed at 28 days in a blinded manner. The effects of BMX-001 on the carotid arterial wall and blood-brain barrier permeability and its interaction with t-PA were assessed in normal rats. There were no intra-group differences in physiological variables. BMX-001-treated stroke rats regained body weight earlier, performed better in behavioral tests, and had smaller brain infarct size compared to the vehicle-treated group. No vascular wall damage and blood-brain barrier permeability changes were detected after the BMX-001 infusion. There was no drug interaction between BMX-001 and t-PA. Intracarotid BMX-001 infusion was safe, and it significantly improved stroke outcomes in rats. These findings indicate that BMX-001 is a candidate drug as an adjunct treatment for thrombectomy procedure to further improve the neurologic outcomes of thrombectomy patients. This study warrants further clinical investigation of BMX-001 as a new stroke therapy.

Heart Rate Response and Locomotor Activity of Female Skateboarders, BIPOC Skateboarders, and Non-skateboard Users During a Typical Session at a Community Skatepark.

Prior research has demonstrated that male adults and youth engaged in skateboarding at community skateparks achieve heart rates that meet or exceed recommendations for exercise by the CDC. However, these studies do not adequately evaluate other non-traditional or ethnically diverse users who may differ in how they utilize the skatepark and in their cardiovascular response. The purpose of this experiment was to measure heart rate response and locomotor movement in three lesser studied groups that frequently utilize community skateparks, and to compare these results with those reported previously in male adult and youth skateboarders. Fifty-six skatepark users were analyzed, including thirty female and BIPOC skateboarders, and twenty-six non-skateboard users. All participants were instrumented with a HR monitor with GPS capability and asked to engage in their preferred activity with no duration specified. Average heart rate and time spent at high and moderate levels of heart rate intensity were not statistically different among the groups studied here, nor were they different from those reported previously for male adult and youth skateboarders. Distances traveled, average, and peak velocities were also not statistically different among the groups studied here, but all were significantly lower than values previously reported for adult male skateboarders. While some differences in distances traveled and velocity were noted, all groups met or exceeded CDC guidelines for cardiovascular fitness. These data suggest that skateparks can help a community achieve health outcomes, particularly among diverse users.

The Redox-Active Manganese(III) Porphyrin, MnTnBuOE-2-PyP5+, Impairs the Migration and Invasion of Non-Small Cell Lung Cancer Cells, Either Alone or Combined with Cisplatin.

Manganese(III) porphyrin MnTnBuOE-2-PyP5+ (MnBuOE, BMX-001) is a third-generation redox-active cationic substituted pyridylporphyrin-based drug with a good safety/toxicity profile that has been studied in several types of cancer. It is currently in four phase I/II clinical trials on patients suffering from glioma, head and neck cancer, anal squamous cell carcinoma and multiple brain metastases. There is yet an insufficient understanding of the impact of MnBuOE on lung cancer. Therefore, this study aims to fill this gap by demonstrating the effects of MnBuOE on non-small cell lung cancer (NSCLC) A549 and H1975 cell lines. The cytotoxicity of MnBuOE alone or combined with cisplatin was evaluated by crystal violet (CV) and/or 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-Tetrazolium (MTS) reduction assays. Intracellular ROS levels were assessed using two fluorescent probes. Furthermore, the impact of MnBuOE alone or in combination with cisplatin on collective cell migration, individual chemotactic migration and chemoinvasion was assessed using the wound-healing and transwell assays. The expression of genes related to migration and invasion was assessed through RT-qPCR. While MnBuOE alone decreased H1975 cell viability at high concentrations, when combined with cisplatin it markedly reduced the viability of the more invasive H1975 cell line but not of A549 cell line. However, MnBuOE alone significantly decreased the migration of both cell lines. The anti-migratory effect was more pronounced when MnBuOE was combined with cisplatin. Finally, MnBuOE alone or combined with cisplatin significantly reduced cell invasion. MnBuOE alone or combined with cisplatin downregulated MMP2, MMP9, VIM, EGFR and VEGFA and upregulated CDH1 in both cell lines. Overall, our data demonstrate the anti-metastatic potential of MnBuOE for the treatment of NSCLC.

Identification of Optimal Movement Patterns for Energy Pumping.

Energy pumping is a way to gain kinetic energy based on an active vertical center of mass movement in rollers in sports like skateboarding, skicross, snowboard cross and BMX. While the principle of the energy transfer from the vertical movement to the horizontal movement is well understood, the question of how to achieve the optimal energy transfer is still unresolved. In this paper, we introduce an inverse pendulum model to describe the movement of the center of mass of an athlete performing energy pumping. On this basis, the problem of identifying the optimal movement pattern is formulated as an optimal control problem. We solve the discretized optimal control problem with the help of a SQP-algorithm. We uncover that the optimal movement pattern consists of a jumping, flying, and landing phase, which has to be timed precisely. We investigate how the maximal horizontal speed depends on parameters like rollers height and maximal normal force of the athlete. Additionally, we present a qualitative comparison of our results with measured results from BMX-racing. For athletes and coaches, we advice on the basis of our results that athlete's performance is optimized by using maximal force and adopt an exact and proper timing of the movement pattern.

Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats.

Introduction Cardiac arrest (CA) and resuscitation induces global cerebral ischemia and reperfusion, causing neurologic deficits or death. Manganese porphyrins, superoxide dismutase mimics, are reportedly able to effectively reduce ischemic injury in brain, kidney, and other tissues. This study evaluates the efficacy of a third generation lipophilic Mn porphyrin, MnTnBuOE-2-PyP5+, Mn(III) ortho meso-tetrakis (N-n-butoxyethylpyridinium-2-yl)porphyrin (MnBuOE, BMX-001), in both mouse and rat models of CA. Methods Forty-eight animals were subjected to 8 min of CA and resuscitated subsequently by chest compression and epinephrine infusion. Vehicle or MnBuOE was given immediately after resuscitation followed by daily subcutaneous injections. Body weight, spontaneous activity, neurologic deficits, rotarod performance, and neuronal death were assessed. Kidney tubular injury was assessed in CA mice. Data were collected by the investigators who were blinded to the treatment groups. Results Vehicle mice had a mortality of 20%, which was reduced by 50% by MnBuOE. All CA mice had body weight loss, spontaneous activity decline, neurologic deficits, and decreased rotarod performance that were significantly improved at three days post MnBuOE daily treatment. MnBuOE treatment reduced cortical neuronal death and kidney tubular injury in mice (p < 0.05) but not hippocampus neuronal death (23% MnBuOE vs. 34% vehicle group, p = 0.49). In rats, they had a better body-weight recovery and increased rotarod latency after MnBuOE treatment when compared to vehicle group (p < 0.01 vs. vehicle). MnBuOE-treated rats had a low percentage of hippocampus neuronal death (39% MnBuOE vs. 49% vehicle group, p = 0.21) and less tubular injury (p < 0.05) relative to vehicle group. Conclusions We demonstrated the ability of MnBuOE to improve post-CA survival, as well as functional outcomes in both mice and rats, which jointly account for the improvement not only of brain function but also of the overall wellbeing of the animals. While MnBuOE bears therapeutic potential for treating CA patients, the females and the animals with comorbidities must be further evaluated before advancing toward clinical trials.

Serious cycling-related fractures in on and off-road accidents: A retrospective analysis in the Australian Capital Territory region.

Cycling is an increasingly popular activity which is widely supported by health advocates. In the last year, more than a third of Australians used a bike [1]. While road cycling remains popular, participation in off-road recreational cycling, including mountain biking, bicycle moto cross (BMX) riding, and outdoor leisure cycling, is increasing and this is associated with an increase in the number and cost of cycling injuries [2-5]. The aim of this study was to describe and compare contemporary patterns of cycling fracture requiring hospitalisation as a function of cycling mode in the Australian Capital Territory region. This retrospective analysis of cycling-related-fracture hospitalisations in the ACT region described data recorded between July 2012 and December 2019. Logistic regression models were used to calculate probabilities of sustaining a fracture at different sites for each of the cycling modes (on-road, mountain, BMX, leisure, unspecified). These likelihoods were then compared against the on-road fracture profile. Cycling-related-fracture hospitalisations increased by 32% in the seven years analysed. Of all fracture admissions, 442 (33%) were on-road, 658 (49%) off-road, and 242 (18%) unknown. The majority were male (79%), median age 37 (IQR 16, 52). Median length of stay was two days. The number of fractures per admission ranged from one to thirteen with a median of one. Wrist, clavicle, ribs, and skull were the four most frequent fracture sites for all cycling modes. Fracture profiles of on- and off-road accidents were similar, with the exception of wrist fractures which were more likely in off-road (OR 1.96, p < 0.01) and unspecified cycling accidents (OR 5.07, p < 0.01). Skull fractures comprised 19% of all BMX-related fractures. More than half of all fracture-related admissions required surgery. With increasing support for sustainable and healthy transport and recreation activities, the fracture profiles of different cycling modes must first be assessed in order to inform strategies to reduce and manage this injury burden.

Ibrutinib Inhibits BMX-Dependent Endothelial VCAM-1 Expression In Vitro and Pro-Atherosclerotic Endothelial Activation and Platelet Adhesion In Vivo.

Introduction: Inflammatory activation of the vascular endothelium leads to overexpression of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), contributing to the pro-thrombotic state underpinning atherogenesis. While the role of TEC family kinases (TFKs) in mediating inflammatory cell and platelet activation is well defined, the role of TFKs in vascular endothelial activation remains unclear. We investigated the role of TFKs in endothelial cell activation in vitro and in a nonhuman primate model of diet-induced atherosclerosis in vivo. Methods and Results: In vitro, we found that ibrutinib blocked activation of the TFK member, BMX, by vascular endothelial growth factors (VEGF)-A in human aortic endothelial cells (HAECs). Blockade of BMX activation with ibrutinib or pharmacologically distinct BMX inhibitors eliminated the ability of VEGF-A to stimulate VCAM-1 expression in HAECs. We validated that treatment with ibrutinib inhibited TFK-mediated platelet activation and aggregation in both human and primate samples as measured using flow cytometry and light transmission aggregometry. We utilized contrast-enhanced ultrasound molecular imaging to measure platelet GPIbα and endothelial VCAM-1 expression in atherosclerosis-prone carotid arteries of obese nonhuman primates. We observed that the TFK inhibitor, ibrutinib, inhibited platelet deposition and endothelial cell activation in vivo. Conclusion: Herein we found that VEGF-A signals through BMX to induce VCAM-1 expression in endothelial cells, and that VCAM-1 expression is sensitive to ibrutinib in vitro and in atherosclerosis-prone carotid arteries in vivo. These findings suggest that TFKs may contribute to the pathogenesis of atherosclerosis and could represent a novel therapeutic target.

Practical use and underlying physics of the BENCHMARK™ BMX™ 96 for large-bore aspiration thrombectomy: Case report of initial institutional experience.

Endovascular thrombectomy (EVT) is part of first-line intervention for acute ischemic stroke management. Recent technological advances have demonstrated that large-bore catheters are an attractive approach for EVT. A multitude of approaches such as A Direct Aspiration first Pass Technique (ADAPT) or in conjunction with stent retrieval (Solumbra technique) have been developed with increasingly large-bore catheters, demonstrating safety and efficacy. Furthermore, these techniques have demonstrated promise for the intervention of cerebral venous thrombosis as well as posterior circulation ischemic events. Recently, advances in neurointerventional catheters have focused on improved maneuverability to navigate the neurovasculature, as well as larger inner diameters for improved procedural versatility, including aspiration. We describe a case report highlighting our early institutional experience with the recently developed large-bore catheter, the BENCHMARK™ BMX™ 96. The case report entails near complete occlusion of the internal carotid artery from acute thrombus and the utility of the BMX™ 96 catheter for treatment of such extensive clot burden. The applicability of large-bore aspiration catheters, with an emphasis on recent advances, for mechanical thrombectomy in arterial as well as venous systems is discussed. To our knowledge, this is the first reported case of use of the BENCHMARK™ BMX™ 96 access system for EVT in acute ischemic stroke. Such new-generation large-bore catheters are a promising advance in neurointervention, and our early institution experience highlights the ease of use and versatility for neurointerventional procedures such as EVT.

CHMFL-BMX-078, a BMX inhibitor, overcomes the resistance of melanoma to vemurafenib via inhibiting AKT pathway.

Our recent study demonstrated eIF3a loss contributes to vemurafenib resistance in melanoma by activating ERK. However, overexpression of eIF3a in the clinic is not feasible to produce vemurafenib re-sensitization, and ERK inhibitors combined with vemurafenib still exhibit limited effectiveness in the treatment of melanoma. Here, using the human receptor tyrosine kinase phosphorylation antibody array, we observed that silencing eIF3a could activate BMX, a tyrosine kinase. The BMX inhibitor CHMFL-BMX-078 could significantly suppress proliferation and induce cell cycle arrest in vemurafenib resistant melanoma cell line A375 (A375R), however, it was hypotoxic in immortal keratinocytes, melanoma cells, and other solid cancer cells such as glioma and breast cancer cells. Furthermore, the combined treatment of CHMFL-BMX-078 and vemurafenib synergistically reduced cell viability and restored the sensitivity of resistant cells to vemurafenib. The reversal of the resistant phenotype by CHMFL-BMX-078 was associated with the AKT signaling pathway, as co-treatment with the AKT activator SC-79 or up-regulation of AKT attenuated the anti-proliferation effect of CHMFL-BMX-078 and vemurafenib. Lastly, we demonstrated that CHMFL-BMX-078 could significantly enhance vemurafenib efficacy in a xenograft model of A375R cells without producing additive toxicity. In conclusion, these findings reveal that the BMX inhibitor CHMFL-BMX-078 may reverse vemurafenib resistance in melanoma by suppressing the AKT signaling pathway, implying that CHMFL-BMX-078 may be a promising compound for overcoming vemurafenib resistance.

Fas signaling in adipocytes promotes low-grade inflammation and lung metastasis of colorectal cancer through interaction with Bmx.

Obesity is a global public health issue. Obesity-related chronic low-grade inflammation (meta-inflammation) can lead to aberrant adipokine release and promote cardiometabolic diseases and obesity-related tumors. However, the mechanisms involved in the initiation of inflammatory responses in obesity and obesity-related tumors as well as metastasis are not fully understood. In this study, we found that the increased tumor necrosis factor-alpha (TNF-α) in adipocytes promoted the lung metastasis of MC38 colon cancer cells via Fas signaling. The release of TNF-α and interleukin (IL)-6 by Fas signaling in adipocytes was caused by the activation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways mediated by the interaction of Fas with Bmx, a non-receptor tyrosine kinase. Moreover, the Fas/Bmx complex is involved in the inflammation of adipocytes via Fas at the Tyr189 site and SH2 domain of Bmx. This is the first study to report the interaction between Fas and Bmx in adipocyte inflammation, which may provide clues for the development of potential new treatment strategies for obesity-related diseases.

Harrogate consensus agreement: Cycling-specific sport-related concussion.

Sport-related concussion (SRC) is a common and increasingly recognised sport-related injury and accounts for between 1% and 9% of all cycling-specific injuries. Attention has been drawn to the difficulty in managing suspected SRC in a fast-paced sport such as road cycling, particularly the lack of an effective and time-efficient assessment protocol. A meeting on cycling SRC was convened in Harrogate, United Kingdom, in an attempt to resolve this problem. The aim was to agree on standard terminology, definitions, diagnostic protocols and return to play protocols for the various differing codes of cycle sport. Seven experts in the field of cycling medicine were invited to participate by the International Cycling Union and are the authors of this report. The panel recognised that the sport of cycling consists of varied disciplines, some of which provide a setting in which a sideline assessment is possible which is in line with the Berlin Consensus statement. However, other disciplines provide challenging circumstances where health care providers have limited access to participants and where participants are unable to discontinue participation and participate in sideline assessment. Consensus-based discipline-specific protocols and guidelines which recognise the limitations posed by these circumstances, but nevertheless, improve on the current situation specific to the sport of cycling are presented as a potential solution to the unique challenges posed by these cycling disciplines.

Worsening of Dizziness Impairment Is Associated with Bone Marrow Kinase on Chromosome X Level in Patients after Mild Traumatic Brain Injury.

Over 2 million people suffer from mild traumatic brain injury (mTBI) each year. Predicting symptoms of mTBI and the characterization of those symptoms has been challenging. Biomarkers that correlate clinical symptoms to disease outcome are desired to improve understanding of the disease and optimize patient care. Bone marrow kinase on chromosome X (BMX), a member of the TEC family of nonreceptor tyrosine kinases, is up-regulated after traumatic neural injury in a rat model of mTBI. The aim of this investigation was to determine whether BMX serum concentrations can effectively be used to predict outcomes after mTBI in a clinical setting. A total of 63 patients with mTBI (Glasgow Coma Score [GCS] between 13 and 15) were included. Blood samples taken at the time of hospital admission were analyzed for BMX. Data collected included demographic and clinical variables. Outcomes were assessed using the Dizziness Handicap Inventory (DHI) questionnaire at baseline and 6 weeks postinjury. The participant was asssigned to the case group if the subject's complaints of dizziness became worse at the sixth week assessment; otherwise, the participant was assigned to the control group. A receiver operating characteristic curve was constructed to explore BMX level. Significant associations were found between serum levels of BMX and dizziness. Areas under the curve for prediction of change in DHI postinjury were 0.76 for total score, 0.69 for physical score, 0.65 for emotional score, and 0.66 for functional score. Specificities were between 0.69 and 0.77 for total score and emotional score, respectively. Therefore, BMX demonstrates potential as a candidate serum biomarker of exacerbating dizziness post-mTBI.

Lactobacillus rhamnosus BMX 54 + Lactose, A Symbiotic Long-Lasting Vaginal Approach to Improve Women's Health.

The proposal to restore vaginal microbiota using biotherapeutic agents ended with controversial results. Vaginal microbiota modifications from eubiosis to dysbiosis (desquamative inflammatory vaginitis, "aerobic vaginitis") and pathobiosis have recently been demonstrated to have a pivotal role in women's clinical health. Bacterial vaginosis (BV) and its related women's pathology seem to be "the most common vaginal infections" in women; the Center for Disease Control (CDC) recommended treatment for this pathology: metronidazole, clyndamicin or other well known treatment such as dequalinium chloride, unfortunately, has been demonstrated to fail in control of this infection and especially in its recurrence rates. A long-lasting vaginal approach with a symbiotic drug (Lactobacillus rhamnosus BMX 54 + lactose) (NORMOGIN™) has demonstrated on a large sample of women enrolled in clinical trials (more than 3000 patients) not only to be able to significantly reduce the BV recurrences, after the CDC standard of care administration, but also to control the vaginal pathobiosis pathway, restoring the physiological eubiosis from dysbiosis. These results are really very encouraging and clearly demonstrate that a symbiotic long-lasting vaginal application of a selected Lactobacillus population plus a prebiotic could be helpful if added to the recommended standard of care.

Power Analysis of Field-Based Bicycle Motor Cross (BMX).

INTRODUCTION: Power meter is a useful tool for monitoring cyclists' training and race performance. However, limited data are available regarding BMX racing power output. The aim of this study was to characterise the power production of BMX riders and investigate its potential role on race performance. METHODS: Fourteen male riders (age: 20.3 ± 1.5 years, height: 1.75 ± 0.05 m, mass: 70.2 ± 6.4 kg) participated in this study. The tests consist of performing two races apart from 15-min recovery. SRM power meter was used to record power and cadence. Cyclists' fastest race was used for the data analysis. Heart rate was recorded at 1-s intervals using a Garmin HR chest strap. Lap time was recorded using four pairs of photocells positioned at the start gate, bottom of the start ramp, end of first corner (time cornering), and on the finish line. RESULTS: There was a large correlation between race time and relative peak power (r = -0.68, p < 0.01) as well as average power with zero value excluded (r = -0.52, p < 0.01). Race time was also significantly associated with time cornering (r = 0.58, p < 0.01). Peak power (1288.7 ± 62.6 W) was reached in the first 2.34 second of the race. With zero values included, the average power was 355.8 ± 25.4 W, which was about 28% of the peak power, compared to 62% when zero values were excluded (795.6 ± 63.5 W). CONCLUSION: The post-race analysis of the power data might help the cyclists recognizing the need to apply certain strategies on pedalling rates and power production in certain portions of the BMX track, specially, at the start and around the first corner. BMX coaches must consider designing training programs based on the race intensity and power output zones.

Serum profiling identifies ibrutinib as a treatment option for young adults with B-cell acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) is a haematological malignancy that is characterized by the uncontrolled proliferation of immature lymphocytes. 80% of cases occur in children where ALL is well understood and treated. However it has a devastating affects on adults, where multi-agent chemotherapy is the standard of care with allogeneic stem cell transplantation for those who are eligible. New treatments are required to extend remission and prevent relapse to improve patient survival rates. We used serum profiling to compare samples from presentation adult B-ALL patients with age- and sex-matched healthy volunteer (HV) sera and identified 69 differentially recognised antigens (P ≤ 0·02). BMX, DCTPP1 and VGLL4 showed no differences in transcription between patients and healthy donors but were each found to be present at higher levels in B-ALL patient samples than HVs by ICC. BMX plays a crucial role in the Bruton's Tyrosine Kinase (BTK) pathway which is bound by the BTK inhibitor, ibrutinib, suggesting adult B-ALL would also be a worthy target patient group for future clinical trials. We have shown the utility of proto-array analysis of B-ALL patient sera, predominantly from young adults, to help characterise the B-ALL immunome and identified a new target patient population for existing small molecule therapy.

New targets for therapy: antigen identification in adults with B-cell acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) in adults is a rare and difficult-to-treat cancer that is characterised by excess lymphoblasts in the bone marrow. Although many patients achieve remission with chemotherapy, relapse rates are high and the associated impact on survival devastating. Most patients receive chemotherapy and for those whose overall fitness supports it, the most effective treatment to date is allogeneic stem cell transplant that can improve overall survival rates in part due to a 'graft-versus-leukaemia' effect. However, due to the rarity of this disease, and the availability of mature B-cell antigens on the cell surface, few new cancer antigens have been identified in adult B-ALL that could act as targets to remove residual disease in first remission or provide alternative targets for escape variants if and when current immunotherapy strategies fail. We have used RT-PCR analysis, literature searches, antibody-specific profiling and gene expression microarray analysis to identify and prioritise antigens as novel targets for the treatment of adult B-ALL.