Maternal Factors and Placental Pathologies Associated with a Diagnosis of Chronic Villitis.

OBJECTIVE: To evaluate maternal risk factors associated with chronic villitis of unknown etiology (VUE) and to describe cooccurring placental pathologies. STUDY DESIGN: A retrospective case-control study was conducted using placental pathology records from deliveries ≥ 20 weeks between 2010 and 2018. Cases were placentas with documented chronic villitis without infectious cause, hereafter called VUE. Controls were placentas without this diagnosis, matched to the cases 2:1. Maternal and neonatal demographic and clinical data were collected. Descriptive statistics are reported with Fisher's exact test or a chi-squared test, as appropriate, and multivariable conditional logistic regression was conducted. RESULTS: Our study included 352 cases with VUE and 657 controls. A diagnosis of gestational diabetes (p = 0.03) and gestational hypertension (p = 0.06) was 1.5 times more likely to occur in those with a VUE diagnosis. A trend was also seen for chronic hypertension (odds ratio [OR] = 1.7, p = 0.07) and preeclampsia (OR = 1.5, p = 0.09) compared with controls. Placentas with VUE, specifically high-grade VUE, were more likely to be small for gestational age (p = 0.01), and to be diagnosed with other placental findings including lymphoplasmacytic or chronic deciduitis (p < 0.01), maternal (p < 0.01) and fetal vascular malperfusion (p = 0.02), and chorionitis (acute or chronic; p < 0.01). CONCLUSION: Gestational diabetes and hypertension were associated with a diagnosis of VUE, and overall, VUE placentas have more abnormal placental findings compared with control. Understanding VUE risk factors may facilitate prenatal care strategies and counseling to achieve the best outcomes for pregnant patients and their neonates. KEY POINTS: · VUE is a common inflammatory lesion of the placenta.. · Gestational diabetes and hypertension are associated with a VUE diagnosis.. · Findings of other placental pathologies increase in VUE..

Increased Fecal Bile Acid Excretion in a Significant Subset of Patients with Other Inflammatory Diarrheal Diseases.

BACKGROUND: Increased fecal bile acid excretion (IBAX) occurs in a third of patients with functional diarrhea. AIMS: To assess the prevalence of IBAX in benign inflammatory intestinal and colonic diseases presenting with chronic diarrhea. METHODS: All patients with known inflammatory diseases or resections who underwent 48 h fecal fat and BA testing for chronic diarrhea at a single center were included. Quiescent disease was based on clinical evaluation and serum, endoscopic and imaging studies. IBAX was defined by: > 2337 µmol total BA/48 h; or primary fecal BAs > 10%; or > 4% primary BA plus > 1000 µmol total BA /48 h. Demographics, fecal weight, fecal fat, stool frequency and consistency were collected. Nonparametric statistical analyses were used for group comparisons. RESULTS: Sixty patients had celiac disease (51 quiescent, 9 active), 66 microscopic colitis (MC: 34 collagenous, 32 lymphocytic), 18 ulcerative colitis (UC), and 47 Crohn's disease (CD). Overall, fecal fat, 48 h stool weight, frequency and consistency were not different among subgroups except for inflammatory bowel disease (IBD) based on disease location. Almost 50% patients with celiac disease and MC had IBAX, with a greater proportion with increased primary fecal BA. Among UC patients, rates of IBAX were higher with pancolonic disease. A high proportion of patients with ileal resection or CD affecting ileum or colon had IBAX. IBAX was present even with quiescent inflammation in UC or CD. CONCLUSIONS: A significant subset of patients with MC, quiescent celiac disease and IBD had increased fecal BA excretion, a potential additional therapeutic target for persistent diarrhea.

Risk of thrombosis in women with cancer undergoing controlled ovarian hyperstimulation for fertility preservation.

PURPOSE: The study aims to evaluate the risk factors and incidence of thromboembolic events among adult women with cancer who underwent controlled ovarian hyperstimulation (COH) for fertility preservation. METHODS: Retrospective, descriptive cohort analysis of patient demographics, medical history, cancer type/treatment, laboratory values, thrombosis within 6 months of COH. RESULTS: 4 of 127 study participants experienced a venous thromboembolic event within 6 months of COH. The median time between oocyte aspiration and the event was 0.25 years (range = 0.10-0.50). The average age at time of event was 25.3 years (SD = 5.3). Three of four thrombotic patients had ovarian cancer, one had breast cancer. All had received surgery and chemotherapy for treatment. All underwent an antagonist cycle ovarian stimulation protocol - none developed ovarian hyperstimulation syndrome. The average anti-mullerian hormone level at the time of hyperstimulation in the thrombosis group was 1.6 (SD = 1.3), compared to 3.6 in the non-thrombosis group. The average max estradiol level reached during ovarian stimulation was 1281.3 (SD = 665.3) in the thrombosis group and 1839.1 (SD = 1513.9) in the non-thrombosis group. Thromboembolic events were not directly associated with mortality. CONCLUSIONS: Within this small descriptive study, the incidence of thromboembolic events in women with cancer undergoing COH for fertility preservation is high. Cancer may play a greater role than COH in thrombosis risk. Ovarian cancer patients who undergo ovarian stimulation may have an increased risk compared to other cancer types. These findings may inform future, prospective studies to determine the role of thromboprophylaxis.

Clinical drug resistance linked to interconvertible phenotypic and functional states of tumor-propagating cells in multiple myeloma.

The phenotype and function of cells enriched in tumor-propagating activity and their relationship to the phenotypic architecture in multiple myeloma (MM) are controversial. Here, in a cohort of 30 patients, we show that MM composes 4 hierarchically organized, clonally related subpopulations, which, although phenotypically distinct, share the same oncogenic chromosomal abnormalities as well as immunoglobulin heavy chain complementarity region 3 area sequence. Assessed in xenograft assays, myeloma-propagating activity is the exclusive property of a population characterized by its ability for bidirectional transition between the dominant CD19(-)CD138(+) plasma cell (PC) and a low frequency CD19(-)CD138(-) subpopulation (termed Pre-PC); in addition, Pre-PCs are more quiescent and unlike PCs, are primarily localized at extramedullary sites. As shown by gene expression profiling, compared with PCs, Pre-PCs are enriched in epigenetic regulators, suggesting that epigenetic plasticity underpins the phenotypic diversification of myeloma-propagating cells. Prospective assessment in paired, pretreatment, and posttreatment bone marrow samples shows that Pre-PCs are up to 300-fold more drug-resistant than PCs. Thus, clinical drug resistance in MM is linked to reversible, bidirectional phenotypic transition of myeloma-propagating cells. These novel biologic insights have important clinical implications in relation to assessment of minimal residual disease and development of alternative therapeutic strategies in MM.

Signs, Sources, Coping Strategies, and Suggested Interventions for Burnout Among Preclerkship Students at a U.S. Medical School: A Qualitative Focus Group Study.

PURPOSE: Research suggests that burnout can begin early in medical school, yet burnout among preclerkship students remains underexplored. This study aimed to characterize burnout signs, sources, coping strategies, and potential interventions among preclerkship students at one U.S. medical school. METHOD: The authors conducted a qualitative study of preclerkship students at Mayo Clinic Alix School of Medicine (MCASOM) during June 2019. Participants completed 2 Maslach Burnout Inventory (MBI) items (measuring frequency of emotional exhaustion and depersonalization) and 2 free-text questions on burnout before participating in 1 of 3 semistructured focus groups. Focus group questions were derived from a literature review on medical student burnout with input from the MCASOM Student Life and Wellness Committee. Group discussions were recorded, transcribed, coded inductively, and analyzed iteratively (along with free-text comments) using a general inductive approach from a constructivist perspective. RESULTS: Eighteen of 111 eligible students (16%) participated, with 5/18 (28%) reporting weekly emotional exhaustion and/or depersonalization on MBI items. Analysis of focus group transcripts showed that most students had experienced burnout symptoms during their first or second year, corresponding with school-related stressors and manifesting in cognitive-emotional, physical, and verbal-behavioral ways. Students identified systemic, institutional, and individual burnout drivers and discussed how these drivers interacted (e.g., high standards of excellence at the system level interacted with anxiety and maladaptive thinking at the individual level, creating pressure to always do more). Students used various coping strategies (e.g., self-care, peer support, reframing, and compartmentalization) but emphasized limitations of these strategies and recommended interventions directed toward systemic and institutional burnout drivers. CONCLUSIONS: This study offers insights into burnout signs and sources among preclerkship medical students that can inform future large-scale studies. Results suggest that burnout emerges from dynamic interactions among systemic, institutional, and individual factors and may benefit from multipronged interventions.

Exploring vital pulp Therapies: A bibliometric analysis of the most cited articles.

Aim: The aim of this study was to identify and analyze the most cited articles on vital pulp therapies. Methodology: Bibliographical data related to the abstract, citations, keywords, and other relevant information was extracted using different combinations of keywords. Further evaluation and visualization of the selected data were performed with the help of various tools, including MS Excel, Microsoft Word, Google open refine, BibExcel, and VOS viewer. An initial search revealed 91 documents, of which 40 were chosen for further analysis. We used the Kolmogorov-Smirnov test and Spearman correlation coefficient test, and our adopted significance level was p < 0.05. Results: In total, the articles received 1,905 citations, with six of them receiving at least 100 citations. Among the top 40 articles, the United States of America (10 articles) and Ireland (6 articles) were the countries with the highest number of cited articles. The journals "Journal of Endodontics" (14 articles; 650 citations) and "International Endodontic Journal" (13 articles; 577 citations) published most of the articles among the 50 most cited ones. Duncan H. was the author with the highest number of works cited (11 articles; 339 citations). Of the articles, systematic reviews accounted for 32%, literature reviews for 14%, in vitro experimental studies for 12%, clinical trials for 8%. Among the biomaterials used in vital pulp therapies, mineral trioxide aggregate (MTA) was discussed in 37 articles (74%), followed by calcium hydroxide, mentioned in 30 studies (60%). Interestingly, the publication year did not demonstrate a significant impact on citation count. Conclusion: The present study provided a detailed list of the top 50 most cited and classic articles on vital pulp therapies. This will help researchers, students, and clinicians in the field of endodontics with an impressive source of information.

Relationship between periapical lesions and sinus changes on multi-slice computed tomography sean.

Differentiating orofacial odontogenic pain/disorders from pain/disorders associated with maxillary sinusitis is important to avoid unnecessary dentalprocedures and to properly refer patients to colleagues/dentists and vice versa. AIM: To analyze the association between apical lesions and sinus changes and to evaluate the agreement between the diagnoses of an endodontist, a radiologist, an oral and maxillofacial surgeon, and an otolaryngologist. MATERIALS AND METHOD: 385 axial, coronal, and sagittal MSCT scans were selected using an image archiving andcommunication system (PACS). The examinations had been performed between 2018 and 2022. RESULTS: Apical lesions were observed in 36.10% of sinusitis cases, 73.8% of unilateralsinusitis cases, 48.7% of sinus floor discontinuity cases, and 67.2% of cases in which endodontic treatment had been performed. Agreement between the diagnoses made by the endodontist and those made by the other investigators was high for most study variables (k > 0.60). The exceptions were mucosal thickening, for which agreement between the endodontist and the other investigators was intermediate (k=0.397), and the presence of periapicallesions (k=0.010), previous endodontic treatment (k=0.013), and mucosal thickness (k=0.024), for which agreement between endodontists and radiologists was low. Conclusions: There was an association between sinus changes and apical lesions.

Diferenciar a dor/desordens odontogénicas orofaciais da dor/desordens as sociadas á sinusite maxilar é importante para evitar procedimentos odontológicos desnecessários e para encaminhar adequadamente os pacientes aos colegas/dentistas e vice-versa. OBJETIVO: Analisar a associagdo entre lesoes apicais e alteragóes sinusais e avaliar a concordáncia entre os diagnósticos de um endodontista, um radiologista, um cirurgido bucomaxilofacial e um otorrinolaringologista. MATERIAL E MÉTODO: foram avaliadas 385 imagens. RESULTADOS: Aslesoes apicais foram observadas em 36,10% dos casos de sinusite, em 73,8% dos casos de sinusite unilateral, em 48,7% dos casos de descontinuidade do assoalho do seio e em 67,2%odos casos em que o tratamento endodontico havia sido realizado. A concordancia entre os diagnósticos feitos pelo endodontista e os feitos pelos outros pesquisadores foi alta para a maioria das variáveis do estudo (k > 0,60). As excegoes foram o espessamento da mucosa, para o qual a concordáncia entre o endodontista e os outros pesquisadores foi intermediária (k=0,397) e a presenga delesoes periapicais (k=0,010), tratamento endodontico prévio (k=0,013) e espessura da mucosa (k=0,024), para os quais a concordáncia entre endodontistas e radiologistas foi baixa. CONCLUSÕES: Houve uma associagdo entre as alteragóes sinusais e aslesoes apicais.

EVI-1 oncogene expression predicts survival in chronic-phase CML patients resistant to imatinib treated with second-generation tyrosine kinase inhibitors.

Activation of the EVI-1 oncogene has been reported in acute myeloid leukemia, chronic myeloid leukemia (CML) in blast crisis, and less commonly, in chronic-phase CML patients. We screened an unselected cohort of 75 chronic-phase CML patients who had failed imatinib for expression of EVI-1 and sought a correlation with subsequent outcome on the second-generation tyrosine kinase inhibitors dasatinib (n = 61) or nilotinib (n = 14). The 8 patients (10.7%) who expressed EVI-1 transcripts detectable by real-time polymerase chain reaction had significantly lower event-free survival, progression-free survival, and overall survival than patients with undetectable transcript. The predictive value of EVI-1 expression was validated in an independent cohort. In a multivariate analysis, EVI-1 expression status and the best cytogenetic response obtained on imatinib were the only independent predictors for overall survival, progression-free survival, and event-free survival. Our data suggest that screening for EVI-1 expression at the time of imatinib failure may predict for response to second-line TKI therapy and consequently aid clinical management.

Regulation of multiple myeloma survival and progression by CD1d.

Down-regulation of conventional human leukocyte antigen (HLA) class I and II molecules from the surface of tumor cells is an important mechanism for tumor immune evasion, survival, and progression. Whether CD1d, a nonconventional, glycolipid-presenting HLA class I-like molecule instructing the function of the immunoregulatory invariant NKT cells can affect tumor cell survival is not known. Here we show that CD1d is highly expressed in premalignant and early myeloma, but with disease progression its expression is reduced and eventually in advanced stages and myeloma cell lines is lost altogether, suggesting that CD1d impacts negatively on myeloma cell survival. Consistent with this, engagement of CD1d by anti-CD1d monoclonal antibodies (mAbs) induces cell death of myeloma cell lines with restored CD1d expression and primary myeloma cells. Cell death induced by monoclonal antibody engagement of CD1d is associated with overexpression of proapoptotic Bax and mitochondrial membrane potential loss but it is caspase-activation independent; in addition, it requires the cytoplasmic tail but not the Tyr residue critical for lysosomal sorting of CD1d. Finally, anti-CD1d cooperates with antimyeloma agents in the killing of myeloma cells. Thus, this work provides evidence linking a novel function of CD1d in the regulation of cell death with tumor survival and progression in humans.

Internet parent-child interaction therapy (I-PCIT) in medically ill child: A case report.

INTRODUCTION: This case illustrates the feasibility, benefit, and putative enhanced ecological validity of performing internet-parent-child interaction therapy (I-PCIT) in the parent-child dyad's home for the treatment of behavior problems in medically ill children in the context of a global pandemic. PATIENT CONCERNS: Parents of a 5-year-old girl initially presented with concerns regarding inattentiveness, physical and verbal fighting with her siblings, and getting kicked out of daycare for hitting another child. Patient also had difficulties sleeping at night. DIAGNOSES: Patient was diagnosed with electrical status epilepticus in sleep, frontal lobe executive function deficit, and attention deficit hyperactivity disorder. INTERVENTIONS: Patient received a course of I-PCIT. Equipment included a cell phone with video capabilities connected to a videotelephony software program and set-up in the child's home by the parents. The treatment course included 8, 1-hour, weekly teaching/coaching sessions (7 of which were performed using I-PCIT) plus 1 follow-up booster session 6 months later. OUTCOMES: Home-based I-PCIT implementation greatly improved disruptive behaviors in a young child with electrical status epilepticus in sleep and attention deficit hyperactivity disorder. CONCLUSION: A combination of I-PCIT and methylphenidate allowed her to be successful at home and in a school setting. More research is needed on PCIT adaptations, such as home-based and internet-based PCIT, for medically ill children as well as treatment protocols for combined therapies.

A Retrospective Examination of the Impact of Pharmacotherapy on Parent-Child Interaction Therapy.

Objective: Parent-child interaction therapy (PCIT) is an evidence-based approach for children aged 2-7 years with disruptive behavior problems. This study examined the effectiveness of PCIT with and without concurrent pharmacotherapy. Methods: A convenience sample was collected from a retrospective chart review of preschool-aged children treated with PCIT at the Mayo Clinic Young Child Clinic between 2016 and 2020. Quantitative and qualitative data were abstracted from all patients. The sample was divided into two groups based on psychotropic medications status (medicated and unmedicated) at the initiation of PCIT. Effectiveness of treatment was assessed with the change in Eyberg Child Behavior Inventory (ECBI) score. The change over time in ECBI score was compared between the two PCIT groups with and without concurrent pharmacotherapy using a linear mixed model. Results: Of the 62 youth, 38.71% were females. Mean age was 4.71 ± 1.17 years. The mean baseline ECBI score was 148.74 ± 30.86, indicating clinically significant disruptive behaviors. The mean number of PCIT sessions was 6.59 ± 3.82. There was no statistically significant difference in ECBI scores between the two groups at pre-PCIT (medication group: 149.68, standard error [SE] = 11.61 vs. unmedicated group: 147.92, SE = 10.93, p = 0.8904) and at post-PCIT (medication group: 116.27 [SE = 11.89] vs. unmedicated group: 128.86 [SE = 11.57], p = 0.3464). There was a statistically significant improvement in ECBI scores for both groups after completing therapy (medication group = -33.41 [-22.32%], SE = 6.27, p < 0.0001; d = 1.144; unmedicated group = -19.06 [-12.88%], SE = 5.78, p = 0.0022; d = 1.078). Conclusions: PCIT reduced disruptive behaviors in this sample of young children regardless of concurrent pharmacotherapy. Future prospective studies should consider one particular pharmacological agent and long-term outcomes of treatment. PCIT and certain pharmacological treatments could have complex and important bidirectional priming effects for both treatments.

Perceptions of Barriers and Facilitators to Becoming a Medical Professional Among Underrepresented Undergraduate and Postbaccalaureate Learners.

OBJECTIVE: To assess underrepresented undergraduate and postbaccalaureate learners' perceptions of (1) the medical field, (2) barriers that might prevent individuals from pursuing professional medical careers, and (3) resources that assist in overcoming these barriers. PARTICIPANTS AND METHODS: A qualitative study with focus groups was designed to achieve the objective. Participants were recruited from a community initiative to provide early exploration of the medical field to disadvantaged and minority individuals. Thirty-five individuals voluntarily participated in semistructured interviews. Audio from the interviews was analyzed using a qualitative descriptive approach and thematic analysis. This study was conducted from October 20, 2018, to April 6, 2019. RESULTS: Participants identified multiple characteristics related to the health care work environment and desirable attributes of health care personnel. The following barriers were identified: financial burden, lacking knowledge of the path to becoming a medical professional, inadequate social support, and lacking the metrics of a competitive candidate. Resources identified by participants to overcome barriers included professional networks and programmatic considerations. CONCLUSION: The study participants discussed negative and positive aspects of the health care environment, such as implicit and explicit biases and attributes that promote or sustain success. Participants expounded on financial, academic, social, and personal factors as barriers to success. In regard to resources that were believed to be helpful to mitigate barriers and promote success, participants commented on activities that simulate a professional medical environment, include networking with medical personnel, support well-being, and provide exposure to structured information on the process of obtaining professional medical training.

Deletions adjacent to BCR and ABL1 breakpoints occur in a substantial minority of chronic myeloid leukemia patients with masked Philadelphia rearrangements.

Deletions at the t(9;22) breakpoint regions, found in 15% of chronic myeloid leukemia patients (CML) with an overt Philadelphia (Ph) translocation, are associated with an adverse disease prognosis in patients receiving interferon-alpha therapy. The incidence of deletions has been shown to vary for different cytogenetic subgroups of CML, with a significantly higher incidence of deletion in patients with a variant Ph translocation. To date, however, the frequency of such deletions in the subgroup of CML patients in whom the BCR/ABL1 fusion arises via submicroscopic chromosomal insertion (masked Ph) has not been investigated. We report the evaluation of 14 patients with masked Ph-positive CML for the presence of deletions extending 3' from BCR and 5' from ABL1 using two triple-color BCR/ABL probes. Deletions were identified in 3 patients (21%), encompassing sequences 5' to ABL1 in two of these and sequences 3' to BCR in the remaining patient, thus demonstrating that the phenomenon is a significant feature of the masked Ph CML subgroup. Furthermore, our findings are consistent with the notion that loss of genomic material is a potential side effect of any DNA breakage event at the 9q34.1 and 22q11.2 chromosomal regions, regardless of the subsequent mechanism of chromosomal rearrangement.

Quality-of-life self-assessment, risk of dysphagia, and swallowing disorders in COVID-19 inpatients / Autoavaliação da qualidade de vida, risco para disfagia e alteração de deglutição em pacientes internados com COVID-19

ABSTRACT Purpose: to identify the impact of swallowing changes and dysphagia complaints on quality-of-life and eating self-assessments of COVID-19 inpatients. Methods: the study comprised 54 COVID-19 inpatients above 18 years old, whose swallowing was clinically assessed by a speech-language-hearing therapist. They were classified regarding food intake (with the FOIS scale) and degree of dysphagia. They also filled out a sample characterization questionnaire and the SWAL-QOL and EAT-10 protocols. Results: the respiratory condition led to worse quality-of-life self-assessment Fatigue results, oral food intake and dysphagia severity classifications. Females had worse quality-of-life self-assessment Burden and Food selection scores. Swallowing complaints were associated with worse eating self-assessments. Patients at risk of dysphagia had worse quality-of-life self-assessments in five out of the 11 domains, worse oral food intake levels, and worse dysphagia severity. Conclusion: COVID-19 inpatients commonly have swallowing complaints and are at risk of dysphagia, with worse quality-of-life self-assessment, lower oral food intake classification, and worse dysphagia severity rating.

RESUMO Objetivos: identificar o impacto de alterações na deglutição e queixa de disfagia na autoavaliação da qualidade de vida e na autoavaliação da alimentação de pacientes internados com COVID-19. Métodos: participaram do estudo 54 indivíduos acima de 18 anos com COVID-19 internados, submetidos à avaliação clínica da deglutição por fonoaudiólogo, classificados em relação à ingestão alimentar pela escala FOIS e grau da disfagia, que preencheram um questionário de caracterização da amostra e os protocolos SWAL-QOL e EAT-10. Resultados: a condição respiratória determinou piores resultados na autoavaliação da qualidade de vida no domínio Fadiga, na definição da ingesta de alimentos via oral e na classificação da gravidade da disfagia. Indivíduos do gênero feminino apresentaram pior autoavaliação da qualidade de vida nos domínios Deglutição como um fardo e Seleção do alimento. Houve associação entre queixa de deglutição e pior autoavaliação da alimentação. Pacientes em risco para disfagia apresentaram pior autoavaliação da qualidade de vida em cinco dos 11 domínios, pior nível de ingesta de alimentos via oral e pior gravidade da disfagia. Conclusão: pacientes internados com COVID-19 comumente apresentam queixas de deglutição e encontram-se em risco para disfagia, apresentando pior autoavaliação da qualidade de vida, menor nível em classificação da escala de ingesta de alimentos via oral e pior classificação da gravidade da disfagia.

Elementos-traço no solo, na planta e no grão de plantas de milho cultivadas em latossolos tratados com lodo de esgoto por 16 anos / Trace elements in soil, plant and grain of corn plants cultivated in Latosols after sixteen years with application of sewage sludge

RESUMO Uma das maiores preocupações quanto à aplicação de lodo de esgoto (LE) no solo se deve à contaminação por elementos-traço, dadas a persistência destes no ambiente e a sua alta toxicidade. O objetivo deste trabalho foi avaliar os teores dos elementos As, Ba, Cd, Cr, Cu, Hg, Mo, Ni, Pb, Se e Zn no solo, na planta e nos grãos do milho, quando plantas foram cultivadas em dois latossolos, após 16 anos com aplicação anual de doses de LE. O experimento foi instalado em condições de campo em Jaboticabal, SP. O delineamento experimental foi em blocos casualizados com quatro tratamentos e cinco repetições. Os tratamentos foram: T1 = 0 testemunha (fertilização mineral, sem aplicação de LE), T2 = 5 t ha-1 LE, T3 = 10 t ha-1 LE e T4 = 20 t ha-1 LE (matéria seca). A aplicação de doses de LE de 10 e 20 t ha-1 aumentou o teor disponível de Cu no latossolo vermelho eutroférrico (LVef) e os teores disponíveis de Cu, Ni, Pb e Zn no latossolo vermelho distrófico (LVd), porém sem ultrapassar os limites estabelecidos pela legislação brasileira (valores de prevenção). Os teores dos elementos As, Ba, Cd, Cr, Hg, Mo e Pb nos grãos de milho permaneceram abaixo dos limites estabelecidos para o consumo humano.

ABSTRACT One of the biggest concerns about the application of sewage sludge to the soil is due to contamination by trace elements, their persistence in the environment and high toxicity. The objective of this work was to evaluate the contents of the elements As, Ba, Cd, Cr, Cu, Hg, Mo, Ni, Pb, Se, and Zn in the soil, the plants, and the grains of corn, when grown in two latosols, after sixteen years with annual application of sewage sludge doses. The experiment was conducted under field conditions in Jaboticabal, SP. The experimental design was randomized blocks with 4 treatments and 5 replications. Treatments were: T1 = 0 control (mineral fertilization, without applying LE), T2 = 5 t ha-1 LE, T3 = 10 t ha-1 LE, and T4 = 20 t ha-1 LE (dry basis). Applying LE doses of 10 and 20 t ha-1 increased the available content of Cu in LVef soil and available levels of Cu, Ni, Pb and Zn in LVd soil, without exceeding the limits established by Brazilian legislation (prevention values). The levels of elements As, Ba, Cd, Cr, Hg, Mo, and Pb in maize grains remained below the limits established for human consumption.

Phenotype of blasts in chronic myeloid leukemia in blastic phase-Analysis of bone marrow trephine biopsies and correlation with cytogenetics.

We identified different phenotypic subsets among 62 cases of chronic myeloid leukemia (CML) in blast crisis (BC) (26% B-lymphoblastic, and 74% various myeloblastic subsets) on bone marrow trephines and correlated the blast-phenotype with cytogenetics. Five of myeloid-BC had an associated 3q26 abnormality and two of these showed a megakaryoblastic-phenotype. While myeloid-BC was associated with additional copies of Philadelphia (Ph) (29%) (p=0.08), numerical abnormalities (51%) (p=0.007), trisomy-8 (29%) (p=0.08) and 17p-loss (22%), none of lymphoid-BC showed these abnormalities. Among myeloid-BC, CD34-negative cases were more often associated with trisomy-8, 17p-loss and numerical abnormalities, and the CD117-negative subset with additional copies of Ph (p<0.05).

Specific patterns of chromosomal gains and losses associate with t(3;14), t(8;14), and t(14;18) in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. Certain chromosomal translocations are associated with clinical outcome, but it is likely that there are both tumor suppressor genes and oncogenes that cooperate with the primary translocations. We have used the Mitelman database to compare chromosomal losses and gains of DLBCL possessing t(14;18), t(8;14), or t(3;14) with DLBCL lacking any of these translocations. The data we obtained are low resolution, but results for t(3;14) validate the methodology. In accord with the literature, loss of 6q was associated with t(3;14). Chromosomes 11, 13, and X were gained significantly in t(3;14), whereas 8p23 was lost. Cases with t(14;18) were associated with gains of chromosomes 7 and 12; cases with t(8;14) were associated with gains of chromosomes 1 and 4.

FISH mapping of Philadelphia negative BCR/ABL1 positive CML.

BACKGROUND: Chronic myeloid leukaemia (CML) is a haematopoietic stem cell disorder, almost always characterized by the presence of the Philadelphia chromosome (Ph), usually due to t(9;22)(q34;q11) or its variants. The Ph results in the formation of the BCR/ABL1 fusion gene, which is a constitutively activated tyrosine kinase. Around 1% of CML patients appear to have a Ph negative karyotype but carry a cryptic BCR/ABL1 fusion that can be located by fluorescence in situ hybridisation (FISH) at chromosome 22q11, 9q34 or a third chromosome. Here we present FISH mapping data of BCR and ABL1 flanking regions and associated chromosomal rearrangements in 9 Ph negative BCR/ABL1 positive CML patients plus the cell line CML-T1. RESULTS: BCR/ABL1 was located at 9q34 in 3 patients, 22q11 in 5 patients and CML-T1 and 22p11 in 1 patient. In 3 of 6 cases with the fusion at 22q11 a distal breakpoint cluster was found within a 280 Kb region containing the RAPGEF1 gene, while in another patient and the CML-T1 the distal breakpoint fell within a single BAC clone containing the 3' RXRA gene. Two cases had a duplication of the masked Ph while genomic deletions of the flanking regions were identified in 3 cases. Even more complex rearrangements were found in 3 further cases. CONCLUSION: BCR/ABL1 formation resulted from a direct insertion (one step mechanism) in 6 patients and CML-T1, while in 3 patients the fusion gene originated from a sequence of rearrangements (multiple steps). The presence of different rearrangements of both 9q34 and 22q11 regions highlights the genetic heterogeneity of this subgroup of CML. Future studies should be performed to confirm the presence of true breakpoint hot spots and assess their implications in Ph negative BCR/ABL1 positive CML.

In vivo kinetics of kinase domain mutations in CML patients treated with dasatinib after failing imatinib.

We sought kinase domain (KD) mutations at the start of treatment with dasatinib in 46 chronic myeloid leukemia (CML) patients resistant to or intolerant of imatinib. We identified BCR-ABL mutant subclones in 12 (26%) cases and used pyrosequencing to estimate subsequent changes in their relative size after starting dasatinib. Four patients lost their mutations, which remained undetectable, 3 patients retained the original mutation or lost it only transiently, 3 lost their original mutations but acquired a new mutation (F317L), and 2 developed another mutation (T315I) in addition to the original mutation within the same subclone. This study shows that expansion of a mutant Ph-positive clone that responds initially to a second generation tyrosine kinase inhibitor may be due either to late acquisition of a second mutation in the originally mutated clone, such as the T315I, or to acquisition of a completely new mutant clone, such as F317L.