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Importantly, HexaBody-DR5/DR5 mediated the highest cytotoxic activity in samples from relapsed/refractory MM patients, including those who are refractory to daratumumab. This improved cytotoxic activity was observed only in patients who received their last anti-MM treatment less then 1 month ago, suggesting that anti-MM drugs sensitized MM cells to HexaBody-DR5/DR5. Supporting this, bortezomib combined with HexaBody-DR5/DR5 synergistically increased cytotoxicity in MM cells in 7 of 11 newly diagnosed patients. Lenalidomide also synergized with HexaBody-DR5/DR5, but only via its immunomodulatory effects, presumably by enhancing the antibody-dependent cellular cytotoxicity activity of HexaBody-DR5/DR5. Daratumumab showed additive effects when combined with HexaBody-DR5/DR5. In conclusion, the results of this preclinical study indicate a therapeutic potential for HexaBody-DR5/DR5, especially in recently treated relapsed/refractory MM patients.In patients with acute myeloid leukemia evolving from myeloproliferative neoplasms (post-MPN-AML), the clinical activity of the B-cell lymphoma 2 inhibitor venetoclax remains to be determined. We review our experience with venetoclax-based regimens in 14 newly diagnosed (frontline [FL]) and 17 relapsed/refractory (R/R) post-MPN-AML patients. Venetoclax was used in combination with hypomethylating agents in 58% of cases and in 19% with intensive chemotherapy (treatment including cytarabine ≥1 g/m2 or CPX-351); the remaining patients received cladribine and low-dose cytarabine or isocitrate dehydrogenase 1/2 inhibitors. The median dose of venetoclax during the initial cycle was 100 mg in all patients (range, 50-800 mg) and 200 mg (range, 100-800 mg) for FL patients. The venetoclax dose was adjusted when used concomitantly with azole antifungal agents. In FL patients, complete remission with and without count recovery in 6 patients (median duration of 6.4 months) and partial remission in 1 patient was noted, with a median overall survival of 7 months. In R/R patients, no formal responses were seen, with a median overall survival of 3 months. Hematologic toxicities and adverse events were frequent; 83% of patients developed grade 3 or higher infection during the initial cycle. selleck Severe hemorrhagic complications were observed in 14 patients, including 6 cases of intracranial and subdural hemorrhage. Overall 4-week and 8-week mortality were 10% and 32%, respectively. Given the substantial treatment-associated hematologic toxicity and mortality, and modest short-lived responses only in newly diagnosed patients with venetoclax-based regimens, additional treatment options are urgently needed for these patients.Many animal species have evolved extreme behaviors requiring them to engage in repeated high-impact collisions. These behaviors include mating displays like headbutting in sheep and drumming in woodpeckers. To our knowledge, these taxa do not experience any notable acute head trauma, even though the deceleration forces would cause traumatic brain injury in most animals. Previous research has focused on skeletomuscular morphology, biomechanics, and material properties in an attempt to explain how animals moderate these high-impact forces. However, many of these behaviors are understudied, and most morphological or computational studies make assumptions about the behavior without accounting for the physiology of an organism. Studying neurophysiological and immune adaptations that co-vary with these behaviors can highlight unique or synergistic solutions to seemingly deleterious behavioral displays. Here, we argue that selection for repeated, high-impact head collisions may rely on a suite of coadaptations in intracranial physiology as a cost-reducing mechanism. We propose that there are three physiological systems that could mitigate the effects of repeated head trauma (i) the innate neuroimmune response, (ii) the glymphatic system, and (iii) the choroid plexus. These systems are interconnected yet can evolve in an independent manner. We then briefly describe the function of these systems, their role in head trauma, and research that has examined how these systems may evolve to help reduce the cost of repeated, forceful head impacts. Ultimately, we note that little is known about cost-reducing intracranial mechanisms making it a novel field of comparative study that is ripe for exploration.Reproduction is linked to a plethora of costs in gravid females, not least of which is a reduction in locomotor performance. Locomotor constraints due to gravidity are apparent across aquatic, terrestrial, and arboreal habitats. Decrements to speed and maneuverability are the most often cited performance consequences of gravidity, regardless of habitat. Arboreal habitats present additional challenges, as they often are composed of unstable and varying substrates that affect locomotor performance. Many arboreal taxa exhibit morphological adaptations, such as grasping extremities and tails, that function to aid in stability during locomotion. Tail length has been found to correlate with lifestyle arboreal mammals tend to have relatively longer tails compared to terrestrial counterparts. Balancing on a limb is hard on its own, but when combined with increased mass and shifts in center of mass due to pregnancy, it becomes even more challenging. However, few studies have explored the constraints that govern the intersection of arboreal locomotion, reproductive cost, and morphology. In this review, we identify fruitful areas for expansion of research and knowledge (i.e. the role of the tail) when it comes to arboreal balance during gestation.
Student-led clinics offer a work-based learning (WBL) opportunity for undergraduate healthcare students to engage with professional activities in a real-life setting. Participation is posited to provide experiential learning and prepare students for clinical practice. This study aims to assess the feasibility of establishing and engaging undergraduate students in one such initiative through the collaboration between one School of Pharmacy and local authority.

The clinic was developed using a logic model and delivered in 2019-2020. A service specification and training were developed and provided to volunteering undergraduate pharmacy students. Anonymised service data were collected and process outcomes around student and public engagement were recorded to assess feasibility for longer-term embedding into the undergraduate programme.

The clinic was operational for 20 days from November 2019 to February 2020. Student volunteers (n = 43, 36.7%) were trained and provided blood pressure screening and healthy living advice to 131 members of the public.
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