Ring chromosome 18 abnormality in acute myelogenous leukemia: the clinical dilemma

The ring chromosome is a circular, structural abnormality composed of either multiple chromosomes or a single chromosome with loss of genetic material at one or both ends. This chromosomal rearrangement is often unstable with frequent recombinations and may be accompanied by either loss or amplification of genetic material[1]. Considering that ring chromosomes are rare in acute myelogenous leukemia (AML), it is difficult to risk stratify patient prognosis, particularly when the ring chromosome occurs as the sole abnormality. Here we report a case of a ring chromosome 18 abnormality in a patient with newly diagnosed AML with monocytic differentiation. Cytogenetic analysis demonstrated 46, XY, r(18)(p11q21) karyotype in 19 of 34 evaluated metaphase cells. The patient received induction chemotherapy and subsequent allogeneic cord blood transplant from a sex-matched donor, and remained in hematologic and cytogenetic remission for 120 days post transplant. Soon after, he developed post transplant lymphoproliferative disorder and died of multi-organ failure. Although r(18) chromosomal abnormalities were not classified in the recent updated evidence-and expert opinion-based recommendations for the diagnosis and management of AML (likely due to the small number of reported cases), the patient was treated as high risk with stem cell transplantation. This was based on the unstable nature of the ring chromosome and the poor outcomes described in the literature of patients with sole ring 18 abnormalities

New insecticide screening platforms indicate that Mitochondrial Complex I inhibitors are susceptible to cross-resistance by mosquito P450s that metabolise pyrethroids

Fenazaquin, pyridaben, tolfenpyrad and fenpyroximate are Complex I inhibitors offering a new mode of action for insecticidal malaria vector control. However, extended exposure to pyrethroid based products such as long-lasting insecticidal nets (LLINs) has created mosquito populations that are largely pyrethroid-resistant, often with elevated levels of P450s that can metabolise and neutralise diverse substrates. To assess cross-resistance liabilities of the Complex I inhibitors, we profiled their susceptibility to metabolism by P450s associated with pyrethroid resistance in Anopheles gambiae (CYPs 6M2, 6P3, 6P4, 6P5, 9J5, 9K1, 6Z2) and An. funestus (CYP6P9a). All compounds were highly susceptible. Transgenic An. gambiae overexpressing CYP6M2 or CYP6P3 showed reduced mortality when exposed to fenpyroximate and tolfenpyrad. Mortality from fenpyroximate was also reduced in pyrethroid-resistant strains of An. gambiae (VK7 2014 and Tiassalé 13) and An. funestus (FUMOZ-R). P450 inhibitor piperonyl butoxide (PBO) significantly enhanced the efficacy of fenpyroximate and tolfenpyrad, fully restoring mortality in fenpyroximate-exposed FUMOZ-R. Overall, results suggest that in vivo and in vitro assays are a useful guide in the development of new vector control products, and that the Complex I inhibitors tested are susceptible to metabolic cross-resistance and may lack efficacy in controlling pyrethroid resistant mosquitoes

Red propolis and its dyslipidemic regulator formononetin: evaluation of antioxidant activity and gastroprotective effects in rat model of gastric ulcer

Propolis has various pharmacological properties of clinical interest, and is also considered a functional food. In particular, hydroalcoholic extracts of red propolis (HERP), together with its isoflavonoid formononetin, have recognized antioxidant and anti-inflammatory properties, with known added value against dyslipidemia. In this study, we report the gastroprotective effects of HERP (50–500 mg/kg, p.o.) and formononetin (10 mg/kg, p.o.) in ethanol and non-steroidal anti-inflammatory drug-induced models of rat ulcer. The volume, pH, and total acidity were the evaluated gastric secretion parameters using the pylorus ligature model, together with the assessment of gastric mucus contents. The anti-Helicobacter pylori activities of HERP were evaluated using the agar-well diffusion method. In our experiments, HERP (250 and 500 mg/kg) and formononetin (10 mg/kg) reduced (p < 0.001) total lesion areas in the ethanol-induced rat ulcer model, and reduced (p < 0.05) ulcer indices in the indomethacin-induced rat ulcer model. Administration of HERP and formononetin to pylorus ligature models significantly decreased (p < 0.01) gastric secretion volumes and increased (p < 0.05) mucus production. We have also shown the antioxidant and anti-Helicobacter pylori activities of HERP. The obtained results indicate that HERP and formononetin are gastroprotective in acute ulcer models, suggesting a prominent role of formononetin in the effects of HERP.This work has been funded by the Fundação de ApoioàPesquisa eàInovação Tecnológica do Estadode Sergipe (FAPITEC/SE), by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).R.L.C.d.A.-J., S.M.T., and J.C.C. received CNPq productivity grants. E.B.S. acknowledges the sponsorship of theproject UIDB/04469/2020 (strategic fund), from the Portuguese Science and Technology Foundation, Ministry ofScience and Education (FCT/MEC) through national funds, and was co-financed by FEDER, under the PartnershipAgreement PT2020. E.N. and A.S. acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D1800014000info:eu-repo/semantics/publishedVersio

Success of an International Learning Health Care System in Hematopoietic Cell Transplantation: The American Society of Blood and Marrow Transplantation Clinical Case Forum

The ASBMT Clinical Case Forum (CCF) was launched in 2014 as an online secure tool to enhance interaction and communication among hematopoietic cell transplantation (HCT) professionals worldwide through the discussion of challenging clinical care issues. After 14 months, we reviewed clinical and demographical data on cases posted in the CCF from 1/29/2014 to 3/18/2015. A total of 137 cases were posted during the study period. Ninety-two cases (67%) were allogeneic HCT, 29 (21%) autologous HCT and in 16 (12%) the type of transplant (auto vs. allo) was still under consideration. The diseases most frequently discussed included non-Hodgkin lymphoma (NHL; n = 30, 22%), acute myeloid leukemia (AML; n = 23, 17%) and multiple myeloma (MM; n = 20, 15%). When compared with the US transplant activity reported by the US Department of Health and Human Services, NHL and acute lymphoblastic leukemia cases were overrepresented in the CCF while myeloma was underrepresented (P < 0.001). A total of 259 topics were addressed in the CCF with a median of two topics/case (range 1-6). Particularly common topics included whether transplant was indicated (n = 57, 41%), conditioning regimen choice (n = 44, 32%), and post-HCT complications after day 100 (n = 43, 31%). The ASBMT CCF is a successful tool for collaborative discussion of complex cases in the HCT community worldwide and may allow identification of areas of controversy or unmet need from clinical, educational and research perspectives

Scoring System Prognostic of Outcome in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome

To develop a system prognostic of outcome in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS)

Changes in the Provision of Institutionalized Mental Health Care in Post-Communist Countries

PMCID: PMC3371010This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Predicting bee community responses to land-use changes: Effects of geographic and taxonomic biases

Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Children and Young Adults with Chronic Myeloid Leukemia: A CIBMTR Cohort Analysis

Chronic myeloid leukemia (CML) in children and young adults is uncommon. Young patients have long life expectancies and low morbidity with hematopoietic cell transplantation (HCT). Prolonged tyrosine kinase inhibitor (TKI) use may cause significant morbidity. In addition indication for HCT in patients in first chronic phase is not established

Maternal outcomes and risk factors for COVID-19 severity among pregnant women.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease