Epidemiology of all-complaint injuries in youth basketball

This study evaluated the incidence and characteristics of all-complaint injuries, including acute and overuse injuries, in female and male youth basketball players. A total of 518 players (16 ± 1.4 years; 38.6% females), from 63 teams, participated in this prospective cohort study. Players were observed through one competitive high school or club basketball season to record exposure and all-complaint injuries, defined as any complaint resulting from participating in basketball-related activities, including but irrespective of the need for medical attention or time loss. Injury incidence rates and rate ratios were derived from Poisson's regression with 99.4% CI (Bonferroni's correction for multiple comparisons). The overall injury incidence rate was 14.4 (99.4% CI: 12.2-17.0) injuries/1000 h; 13.8 (99.4% CI: 11.2-16.8) in females and 14.8 (99.4% CI: 11.7-18.8) in males. While the incidence of injury was similar across injury classifications for female and male players, a potential lower overuse knee injury rate was noted for females vs males [IRR = 0.61 (99.4% CI: 0.34-1.07)]. The most commonly injured body location was the ankle (45%) in females and the knee (51%) in males. Overuse (vs acute) injuries were about 2x more common in the knee while acute (vs overuse) injuries were about 3x more common in the ankle, overall, and for female and male players. Based on an all-complaint injury definition, injury rates in competitive female and male youth basketball players are much higher than previously reported. This study provides an evidence base to inform more tailored interventions to reduce injuries in youth basketball.     

Systematic Review of l-glutamine for Prevention of Vaso-occlusive Pain Crisis in Patients with Sickle Cell Disease

l -glutamine was approved by the U.S. Food and Drug Administration (FDA) for sickle cell disease (SCD) in 2017. A vaso-occlusive crisis (VOC) occurs in persons with SCD and is associated with acute pain episodes. This systematic review summarizes the evidence for l -glutamine in the prevention of VOC and associated pain in patients with SCD. Medline, Embase, and International Pharmaceutical Abstracts were searched for records reporting on l -glutamine use in persons with SCD. Eligibility criteria identified primary reports of investigations conducted in humans who were administered l -glutamine, reported on outcomes related to VOC or associated pain, published in English, and were available as full text. All relevant efficacy, safety, participant demographic data, and study method characteristics were extracted and documented. Risk-of-bias assessments were conducted using the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) tool and the revised Cochrane risk-of-bias tool for randomized studies. Three studies assessing the effect of exogenous l -glutamine administration in patients with SCD met eligibility criteria: one prospective nonrandomized controlled study and two prospective randomized controlled trials. Rate of VOC and related hospitalizations were reduced in patients receiving l -glutamine, although some conflicting results were noted between studies. l -glutamine was generally well tolerated. Limitations of one or more of the eligible studies included small sample size, nonblinding, and study groups that differed at baseline. l -glutamine has limited high-quality evidence supporting its use. Although l -glutamine is FDA approved for the prevention of frequent episodes of VOC pain, only one randomized controlled trial has strong evidence to support this indication. Based on the results of a systematic review, l -glutamine may be considered for patients unable to receive hydroxyurea or in addition to hydroxyurea for reduction in VOC and associated pain.     

Pevonedistat and azacitidine upregulate NOXA (PMAIP1) to increase sensitivity to venetoclax in preclinical models of acute myeloid leukemia

Dysregulation of apoptotic machinery is one mechanism by which acute myeloid leukemia (AML) acquires a clonal survival advantage. B-cell lymphoma protein-2 (BCL2) overexpression is a common feature in hematologic malignancies. The selective BCL2 inhibitor, venetoclax (VEN) is used in combination with azacitidine (AZA), a DNAmethyltransferase inhibitor (DNMTi), to treat patients with AML. Despite promising response rates to VEN/AZA, resistance to the agent is common. One identified mechanism of resistance is the upregulation of myeloid cell leukemia-1 protein (MCL1). Pevonedistat (PEV), a novel agent that inhibits NEDD8-activating enzyme, and AZA both upregulate NOXA (PMAIP1), a BCL2 family protein that competes with effector molecules at the BH3 binding site of MCL1. We demonstrate that PEV/AZA combination induces NOXA to a greater degree than either PEV or AZA alone, which enhances VEN-mediated apoptosis. Herein, using AML cell lines and primary AML patient samples ex vivo, including in cells with genetic alterations linked to treatment resistance, we demonstrate robust activity of the PEV/VEN/AZA triplet. These findings were corroborated in preclinical systemic engrafted models of AML. Collectively, these results provide rational for combining PEV/VEN/AZA as a novel therapeutic approach in overcoming AML resistance in current therapies.     

Moving beyond Definitive Therapy: Increasing Physical Activity in Survivors of Cancers of the Head and Neck

As chemotherapeutic, radiation, and surgical techniques have improved, there has been a dramatic improvement in survival in patients diagnosed with cancers of the head and neck. As a result, a heightened focus on survivorship by clinicians will increasingly prove necessary. In particular, medical care teams will have to pay special attention to mitigating the long-term sequelae of definitive cancer treatments, many of which act as barriers to exercise. This is unfortunate, as the benefits of exercise in patients with cancer have become increasingly recognized. In this review, we discuss the potential benefits of and barriers to exercise in survivors of cancers of the head and neck. We also review existing exercise guidelines and strategies by which clinicians can promote exercise in this unique patient population.     

The berkeleyamides, amides from the acid lake fungus Penicillum rubrum

We previously reported several novel bioactive hybrid polyketide-terpenoid metabolites from a deep water Penicillium rubrum isolated from Berkeley Pit Lake, Butte, Montana. In this paper we report the structures of four new amides, berkeleyamides A-D (1, 4, 5, 7), isolated from extracts of this fungus. The structures of these compounds were deduced by analysis of NMR data, chemical derivatization, and comparison of their spectroscopic data to those of known compounds.