Child Maltreatment, Exposure to Violence, and Adolescent Weapon Carrying

This study examined associations between child maltreatment, violence exposure, and gender in predicting subsequent adolescent weapon carrying. Data from the National Survey of Child and Adolescent Well- Being, a nationally representative longitudinal study of families in contact with the child welfare system, were used. Participants included 821 youth who were followed over five years. Results from a logistic regression suggested that male youth who reported physical abuse at baseline were less likely to report carrying a weapon any time across the follow up period, while physical abuse did not predict weapon carrying in females. These counterintuitive findings demonstrated a complex relationship between violence exposure and subsequent risk behaviors among a vulnerable population of youth

The foreign language textbook : an evaluation proposal

Este artigo, preocupado com a frequente carência de critérios por parte dos professores de língua estrangeira no momento da escolha de seu material didático, apresenta uma proposta de análise de livros didáticos, tendo como base teórica principal os Parâmetros Curriculares Nacionais – Língua Estrangeira – 5ª a 8ª séries. Essa proposta, organizada em cinco fichas, compostas de uma série de perguntas norteadoras, foi criada com o intento de tornar os conceitos presentes nos PCN menos abstratos. O trabalho sugere que a proposta de avaliação, aqui apresentada, não deve ser utilizada como receita, mas como objeto de reflexão, no momento da escolha do livro didático, por parte dos profissionais do ensino de língua estrangeira.Foreign language teachers lack criteria when the time comes for them to choose the book to use in their classrooms. Thus, this paper tries to offer these teachers a series of guidelines based on the “National Curriculum Guidelines – Foreign Languages - Grades 5 through 8”. This proposal, divided into five cards composed of several guiding questions, was then created with the intention of making the concepts related to that document less abstract than they are in those Guidelines. The study suggests that foreign language professionals should not use this proposal as a recipe, but as an object for reflection while choosing the materials to be used in their classrooms

Entering a Community of Writers: The Writing Center, Doctoral Students, and Going Public with Scholarly Writing

In addition to taking advanced courses, graduate students navigate a potentially challenging transition of learning to write for publication. We, the authors, explored solutions to this transition with a study designed to explore the research questions: How does a systematic effort to help doctoral students enter a community of writers via writing center collaboration influence doctoral students’: (1) proficiency with academic writing, (2) writing apprehension, (3) self-efficacy as writers, and (4) comfort with “going public” with their writing? We used a collaborative, multi-layered self-study research approach because it allowed us to focus on critical examination of teaching practices that are of interest to the practitioner/researcher and to the greater educational community. Authors/participants include the co-director of a university Writing Center; two professors of a doctoral-level qualitative research methods course; four doctoral students who participated in a series of writing center collaborations; and one master’s student who served as a writing center consultant. These four perspectives provide unique insights into how writing center collaborations supported graduate students in developing their writing proficiency and efficacy, helping to initiate them into a community of writers who “go public” with their scholarship

Stapled EGFR peptide reduces inflammatory breast cancer and inhibits additional HER-driven models of cancer

Background: The human epidermal growth factor receptor (HER) family of transmembrane tyrosine kinases is overexpressed and correlates with poor prognosis and decreased survival in many cancers. The receptor family has been therapeutically targeted, yet tyrosine kinase inhibitors (TKIs) do not inhibit kinase-independent functions and antibody-based targeting does not affect internalized receptors. We have previously demonstrated that a peptide mimicking the internal juxtamembrane domain of HER1 (EGFR; EJ1) promotes the formation of non-functional HER dimers that inhibit kinase-dependent and kinase-independent functions of HER1 (ERBB1/EGFR), HER2 (ERBB2) and HER3 (ERBB3). Despite inducing rapid HER-dependent cell death in vitro, EJ1 peptides are rapidly cleared in vivo, limiting their efficacy. Method: To stabilize EJ1 activity, hydrocarbon staples (SAH) were added to the active peptide (SAH-EJ1), resulting in a 7.2-fold increase in efficacy and decreased in vivo clearance. Viability assays were performed across HER1 and HER2 expressing cell lines, therapeutic-resistant breast cancer cells, clinically relevant HER1-mutated lung cancer cells, and patient-derived glioblastoma cells, in all cases demonstrating improved efficacy over standard of care pan-HER therapeutics. Tumor burden studies were also performed in lung, glioblastoma, and inflammatory breast cancer mouse models, evaluating tumor growth and overall survival. Results: When injected into mouse models of basal-like and inflammatory breast cancers, EGFRvIII-driven glioblastoma, and lung adenocarcinoma with Erlotinib resistance, tumor growth is inhibited and overall survival is extended. Studies evaluating the toxicity of SAH-EJ1 also demonstrate a broad therapeutic window. Conclusions: Taken together, these data indicate that SAH-EJ1 may be an effective therapeutic for HER-driven cancers with the potential to eliminate triple negative inflammatory breast cancer.Arizona Cancer Therapeutics; Ginny L Clements Breast Cancer Research Fund; NIH [NIH 1R41CA203353]; NCI [P30 CA023074]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Prognostic impact of pretransplant measurable residual disease assessed by peripheral blood WT1-mRNA expression in patients with AML and MDS

OBJECTIVE As peripheral blood (PB) Wilm's Tumor 1 (WT1)-mRNA expression is established as MRD-marker during conventional AML chemotherapy, impact of pretransplant WT1 expression remains unclear. Therefore, we aimed to assess prognostic impact of pretransplant WT1 expression on post-transplant outcome in patients with AML/MDS. METHODS In 64 AML/MDS patients, pretransplant WT1 expression was retrospectively analyzed using a standardized assay offering high sensitivity, specificity, and a validated cut-off. Patients were divided into three groups determined by pretransplant remission and WT1 expression. Post-transplant outcome of these groups was compared regarding cumulative incidence of relapse (CIR), relapse-free (RFS), and overall survival (OS). RESULTS Pretransplant forty-six patients (72%) showed hematologic remission, including 21 (46%) MRD-negative and 25 (54%) MRD-positive patients indicated by WT1 expression, while 18 refractory patients (28%) showed active disease. Two-year estimates of post-transplant CIR, RFS, and OS were similar in MRD-positive (61%, 37%, 54%) and refractory patients (70%, 26%, 56%), but significantly inferior compared with MRD-negative patients (10%, 89%, 90%). After multivariable adjustment, pretransplant MRD negativity measured by WT1 expression retained its prognostic impact on CIR (P~=~.008), RFS (P~=~.005), and OS (P~=~.049). CONCLUSIONS PB WT1 expression represents a useful method to estimate pretransplant MRD, which is highly predictable for post-transplant outcome and may help improving peri-transplant management in AML/MDS patients

Good neurological outcome despite very low regional cerebral oxygen saturation during resuscitation - a prospective preclinical trial in 29 patients

Background Noninvasive regional cerebral oxygen saturation (rSO2) measurement using near-infrared spectroscopy (NIRS) might inform on extent and duration of cerebral hypoxia during cardiopulmonary resuscitation (CPR). This information may be used to guide resuscitation efforts and may carry relevant early prognostic information. Methods We prospectively investigated non-traumatic out-of-hospital cardiac arrest (OHCA) patients on scene. NIRS was started either during CPR or shortly after (<2 min) return of spontaneous circulation (ROSC) by emergency medical service (EMS). Outcome was determined at intensive care unit (ICU) discharge and 6 months after cardiac arrest. Results A total of 29 OHCA patients were included. In 23 patients NIRS was started during CPR and in 6 patients immediately after ROSC. 18 (62.1 %) patients did not reach ROSC. Initial rSO2 during CPR was very low (<50 % in all 23 patients, < 30 % in 19 of 23 patients) with no significant difference between patients achieving ROSC and those who did not. Of five patients with ROSC, in whom NIRS was recorded during CPR, two reached a good six-months outcome (initial rSO2 22 %) and three died during the ICU stay (initial rSO2 15, 16 and 46 %). In six patients with NIRS started immediately after ROSC (<2 min), rSO2 was substantially higher (54–85 %) than in patients during CPR (p = 0.006). Discussion and conclusion Initial frontal brain rSO2 determined by NIRS during CPR was generally very low and recovered rapidly after ROSC. Very low initial rSO2 during CPR was compatible with good neurological outcome in our limited cohort of patients. Further studies are needed to assess in larger cohorts and more detail the implications of very low initial rSO2 during CPR on scene

Fast and slow gating are inherent properties of the pore module of the K+ channel Kcv

Kcv from the chlorella virus PBCV-1 is a viral protein that forms a tetrameric, functional K+ channel in heterologous systems. Kcv can serve as a model system to study and manipulate basic properties of the K+ channel pore because its minimalistic structure (94 amino acids) produces basic features of ion channels, such as selectivity, gating, and sensitivity to blockers. We present a characterization of Kcv properties at the single-channel level. In symmetric 100 mM K+, single-channel conductance is 114 ± 11 pS. Two different voltage-dependent mechanisms are responsible for the gating of Kcv. “Fast” gating, analyzed by β distributions, is responsible for the negative slope conductance in the single-channel current–voltage curve at extreme potentials, like in MaxiK potassium channels, and can be explained by depletion-aggravated instability of the filter region. The presence of a “slow” gating is revealed by the very low (in the order of 1–4%) mean open probability that is voltage dependent and underlies the time-dependent component of the macroscopic current

Nucleocytosolic depletion of the energy metabolite acetyl-coenzyme a stimulates autophagy and prolongs lifespan.

Healthy aging depends on removal of damaged cellular material that is in part mediated by autophagy. The nutritional status of cells affects both aging and autophagy through as-yet-elusive metabolic circuitries. Here, we show that nucleocytosolic acetyl-coenzyme A (AcCoA) production is a metabolic repressor of autophagy during aging in yeast. Blocking the mitochondrial route to AcCoA by deletion of the CoA-transferase ACH1 caused cytosolic accumulation of the AcCoA precursor acetate. This led to hyperactivation of nucleocytosolic AcCoA-synthetase Acs2p, triggering histone acetylation, repression of autophagy genes, and an age-dependent defect in autophagic flux, culminating in a reduced lifespan. Inhibition of nutrient signaling failed to restore, while simultaneous knockdown of ACS2 reinstated, autophagy and survival of ach1 mutant. Brain-specific knockdown of Drosophila AcCoA synthetase was sufficient to enhance autophagic protein clearance and prolong lifespan. Since AcCoA integrates various nutrition pathways, our findings may explain diet-dependent lifespan and autophagy regulation

Diagnosis, risk factors and pathogenesis of preeclampsia

A pré-eclâmpsia é uma doença da gestação que pode determinar restrição no crescimento fetal, prematuridade e, em casos mais graves, morte da mãe e do feto. Caracteriza-se por hipertensão arterial materna, proteinúria significativa (? 0,3g/24h), edema, vaso-constrição do leito vascular materno e conseqüente aumento da resistência vascular. Muitos estudos discutem fatores de risco, patogê-nese e critérios para o diagnóstico da pré-eclampsia, porém as variações na forma de apresentação e de evolução clínica dessa doença dificultam o entendimento dos resultados obtidos, freqüentemente conflitantes. A padronização diagnóstica e as pesquisas de base genética e molecular podem trazer, em um futuro próximo, maior compreensão dessa patologia. Neste artigo apresentamos uma revisão da literatura, com destaque para a relação entre pré-eclâmpsia e resistência à insulina.Preeclampsia is an illness of the gestation that involves fetal growth restriction, prematurity and, in more severe cases, death of mother and fetus. It is characterized by maternal hypertension, significant proteinuria (? 0,3g/24 h), edema, vasoconstriction of maternal blood vessels and consequent increase in vascular resistance. Many studies discuss risk factors, pathogenesis and diagnostic criteria of preeclampsia; however, there are large variations in presentation and clinical course of this illness, which make interpretation of fre-quently conflicting results difficult. Diagnostic standardization and research of genetic and molecular bases can bring a better understand-ing of this pathology in a near future. In this paper, we present a review of the literature, stressing the relation between preeclampsia and insulin resistance

Dietary spermidine for lowering high blood pressure

Loss of cardiac macroautophagy/autophagy impairs heart function, and evidence accumulates that an increased autophagic flux may protect against cardiovascular disease. We therefore tested the protective capacity of the natural autophagy inducer spermidine in animal models of aging and hypertension, which both represent major risk factors for the development of cardiovascular disease. Dietary spermidine elicits cardioprotective effects in aged mice through enhancing cardiac autophagy and mitophagy. In salt-sensitive rats, spermidine supplementation also delays the development of hypertensive heart disease, coinciding with reduced arterial blood pressure. The high blood pressure-lowering effect likely results from improved global arginine bioavailability and protection from hypertension-associated renal damage. The polyamine spermidine is naturally present in human diets, though to a varying amount depending on food type and preparation. In humans, high dietary spermidine intake correlates with reduced blood pressure and decreased risk of cardiovascular disease and related death. Altogether, spermidine represents a cardio- and vascular- protective autophagy inducer that can be readily integrated in common diets