School Counselors\u27 Perceptions of Trauma-Informed Approaches in Schools

Adverse childhood experiences affect millions of children and adults on a daily basis and this results in many people who are unable to effectively navigate the pathways of life to lead a productive life. Schools are in an ideal position to intercede and provide trauma-informed care to children who are experiencing academic or behavioral problems by providing programs aimed at decreasing the effects of these adverse experiences. One such program being implemented is the multi-tiered support system (MTSS) programs, which is incorporated into the entire school day of all students. Interventions are provided in tiers which correspond to the needs of each student. Evidence-based interventions are provided while the results are monitored and used to provide further assistance. School counselors are an integral part of the MTSS team, which includes PBIS and RtI components, but often they do not receive the necessary training. When school counselors are adequately trained, they function as a team member and this increases the amount of time counselors can spend on other important activities

Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective Collaboration, Current Knowledge, and Challenges Ahead

Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse

Alternative Splicing in the Obligate Biotrophic Oomycete Pathogen Pseudoperonospora cubensis

Pseudoperonospora cubensis is an obligate pathogen and causative agent of cucurbit downy mildew. To help advance our understanding of the pathogenicity of P. cubensis, we used RNA-Seq to improve the quality of its reference genome sequence. We also characterized the RNA-Seq dataset to inventory transcript isoforms and infer alternative splicing during different stages of its development. Almost half of the original gene annotations were improved and nearly 4,000 previously unannotated genes were identified. We also demonstrated that approximately 24% of the expressed genome and nearly 55% of the intron-containing genes from P. cubensis had evidence for alternative splicing. Our analyses revealed that intron retention is the predominant alternative splicing type in P. cubensis, with alternative 5′- and alternative 3′-splice sites occurring at lower frequencies. Representatives of the newly identified genes and predicted alternatively spliced transcripts were experimentally validated. The results presented herein highlight the utility of RNA-Seq for improving draft genome annotations and, through this approach, we demonstrate that alternative splicing occurs more frequently than previously predicted. In total, the current study provides evidence that alternative splicing plays a key role in transcriptome regulation and proteome diversification in plantpathogenic oomycetes

Substance Use Among Persons with Syphilis During Pregnancy - Arizona and Georgia, 2018-2021

Despite universal prenatal syphilis screening recommendations and availability of effective antibiotic treatment, syphilis prevalence during pregnancy and the incidence of congenital syphilis have continued to increase in the United States (1,2). Concurrent increases in methamphetamine, injection drug, and heroin use have been described in women with syphilis (3). CDC used data on births that occurred during January 1, 2018-December 31, 2021, from two states (Arizona and Georgia) that participate in the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET) to describe the prevalence of substance use among pregnant persons with syphilis by congenital syphilis pregnancy outcome (defined as delivery of a stillborn or live-born infant meeting the surveillance case definition for probable or confirmed congenital syphilis). The prevalence of substance use (e.g., tobacco, alcohol, cannabis, illicit use of opioids, and other illicit, nonprescription substances) in persons with a congenital syphilis pregnancy outcome (48.1%) was nearly double that among those with a noncongenital syphilis pregnancy outcome (24.6%). Persons with a congenital syphilis pregnancy outcome were six times as likely to report illicit use of opioids and four times as likely to report using other illicit, nonprescription substances during pregnancy than were persons with a noncongenital syphilis pregnancy outcome. Approximately one half of persons who used substances during pregnancy and had a congenital syphilis pregnancy outcome had late or no prenatal care. Tailored interventions should address barriers and facilitators to accessing screening and treatment for syphilis among persons who use substances. The need for syphilis screening and treatment should be addressed at any health care encounter during pregnancy, especially among persons who use substances

Carbon-Carbon bond forming reactions of organotransition metal enolate complexes

Abstract -Metal enolates play an important role in stereoselective organic synthesis. Their chemistry is affected profoundly by the metal counterion associated with the enolate fragment. In order to expand the potential of replacing main group with transition metal moieties in such species, methods have been developed for the synthesis of a number of stable, characterizable "late" transition metal ql-(C)-enolate complexes having the general structure LM-CH2COR (M = Mo, W, Re). The chemistry of these materials (e.g., functional transformations of the organic carbonyl group, transfer of the enolate moietry to organic substrates such as aldehydes and alkynes) has been investigated. The scope and mechanisms of the enolate reactions will be discussed in detail. The reaction of organic enolates with carbon electrophiles (e.g., alkyl halides, organic carbonyl compounds) gives rise to compounds containing new carbon-carbon bonds; reaction with heteroatom electrophiles results in the formation of oxidized products? There has been much interest recently in developing methods for carrying out these transformations with high stereoselectivity.3 Historically, most enolate research has focused on salts involving alkali metal anions. More recently, research efforts have been extended to enolates associated with organic cations, main group metals, and transition metals. In the transition metal area, enolates involving the so-called "early" metals (to the left of chromium, molybdenum and tungsten) have seen extensive investigationi4 in general these complexes have 0-bonded structures A in Scheme 1. This paper describes the synthesis and chemistry of middle-and late transition metal enolates, which have seen less investigation. It was our hope that such species would be more likely to have Cbound structure B, and also to react with both electrophilic and non-electrophilic species (e.g., by insertion rather than nucleophile-electrophile mechanisms). SYNTHESIS, CHARACTERIZATION AND FUNCTIONAL GROUP TRANSFORMATIONS OF TUNGSTEN AND MOLYBDENUM ENOLATES The well-known nucleophilic anionic metal salts5 Na[(qS-C5R5)(C0)3M] (M = Mo, W, R=H, Me), on treatment with a-chloroketones and esters, provide good yields of enolates 1 -8, as shown in Scheme 2. These are thermally stable complexes that may be isolated by conventional chromatographic and recrystallization methods; they have been characterized fully by elemental analysis and spectroscopic techniques. Preparation of these materials on a multi-gram scale in a one-pot procedure is possible by treatment of W(CO)6 or Mo(C0)6 with NaCp, followed by addition of the a-chlorocarbonyl compound to the resulting metal anion solution. The stability of the tungsten-carbon bond in tungsten ester enolates, fiist suggested several years ago by the work of Green and his coworkers6, has allowed us to carry out a wide range of transformations on the organic carbonyl group. Thus the reactions shown in Scheme 3 proceed in good yield, and lead to stable tungsten enolates containing ester, amide and even carboxylic acid and acid chloride functionality

CD40L-Tri, a novel formulation of recombinant human CD40L that effectively activates B cells

CD40L has a well-established role in enhancing the immunostimulatory capacity of normal and malignant B cells, but a formulation suitable for clinical use has not been widely available. Like other TNF family members, in vivo and in vitro activity of CD40L requires a homotrimeric configuration, and growing evidence suggests that bioactivity depends on higher-order clustering of CD40. We generated a novel formulation of human recombinant CD40L (CD40L-Tri) in which the CD40L extracellular domain and a trimerization motif are connected by a long flexible peptide linker. We demonstrate that CD40L-Tri significantly expands normal CD19+ B cells by over 20- to 30-fold over 14 days and induces B cells to become highly immunostimulatory antigen-presenting cells (APCs). Consistent with these results, CD40L-Tri-activated B cells could effectively stimulate antigen-specific T responses (against the influenza M1 peptide) from normal volunteers. In addition, CD40L-Tri could induce malignant B cells to become effective APCs, such that tumor-directed immune responses could be probed. Together, our studies demonstrate the potent immune-stimulatory effects of CD40L-Tri on B cells that enable their expansion of antigen-specific human T cells. The potent bioactivity of CD40L-Tri is related to its ability to self-multimerize, which may be facilitated by its long peptide linker. Electronic supplementary material The online version of this article (doi:10.1007/s00262-012-1331-4) contains supplementary material, which is available to authorized users

The EHA Research Roadmap : Malignant Lymphoid Diseases

Peer reviewe

Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes