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Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.Accumulation of non-essential heavy metals like chromium (Cr) is among major abiotic stresses, which adversely affect crop growth. Hexavalent chromium [Cr(VI)] is the most dangerous form negatively affecting the growth and productivity of crops. This study evaluated the role of black cumin extracts (BCE) in improving growth and productivity of maize genotypes under different concentrations of Cr(VI). Two maize genotypes ("Neelum" and "P1543") were grown under 0, 4, 8 and 12 mg Cr(VI) kg-1 concentrations. The BCE was applied as foliar spray at three concentrations (0, 10 and 20%) at 25 and 45 days after sowing. Increasing Cr(VI) concentration significantly (p less then 0.05) reduced seed germination, root and allometric traits, gas exchange attributes and relative water contents of tested genotypes. Hybrid maize genotype better tolerated tested Cr(VI) concentrations than synthetic genotype with lower Cr accumulation and better allometric and gas exchange traits. Exogenous application of 20% BCE proved effective in lowering the adverse effects of Cr(VI) toxicity on maize genotypes. It is concluded that 20% BCE could be used to improve maize performance through better allometric and gas exchange traits under different Cr(VI) concentrations. Nonetheless, actual mechanisms involved in improved Cr(VI)-tolerance of maize with BCE application must be explored. Novelty statement Black cumin has been widely used to reduce Cr toxicity in animals. However, the role of black cumin in reducing Cr toxicity in plants has never been studied. The present study was conducted to infer the role of different concentrations of black cumin extract in improving the growth of synthetic and hybrid maize genotypes under different levels of Cr stress. It is concluded that black cumin extract could be used to lower Cr toxicity in maize grown under Cr-contaminated soils.
The purpose of this study was to evaluate the efficacy and safety of different doses of anthracyclines combined with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) for induction in newly diagnosed acute promyelocytic leukemia (APL).
One hundred and forty patients were included between January 2011 and December 2017. Seventy patients received low dose anthracycline, ATO and ATRA for induction chemotherapy; and other seventy patients received standard dose anthracycline, ATO and ATRA for induction chemotherapy.
The outcomes of both groups were similar low dose group versus standard dose group early mortality 5.7% vs. 10.0% (
= 0.532), disease-free survival (DFS), probabilities of overall-survival (OS) at 2 years 94.6% vs. 95.1% (
= 0.657), 92.8% vs. 88.2% (
= 0.951), respectively. However, the standard-dose group was associated with a longer duration of neutropenia (
< 0.001) and thrombocytopenia (
< 0.001), more volumes of platelets (
= 0.037) and red blood cell transfusions (
< 0.001), and a higher rate of infections (
= 0.042).
Low-dose group achieves outcomes similar to those of standard dose group for APL patients, but the low-dose group may be even safer than standard-dose group. So the low-dose anthracycline may be a better choice for newly diagnosed APL patients.
Low-dose group achieves outcomes similar to those of standard dose group for APL patients, but the low-dose group may be even safer than standard-dose group. So the low-dose anthracycline may be a better choice for newly diagnosed APL patients.Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in acute myelogenous leukemia (AML) and the mutation is associated with poor prognosis of patients. Two distinct types of activating mutations have been identified in AML samples. learn more One is internal tandem duplications in the juxtamembrane domain (FLT3-ITD) and the other is point mutations in the tyrosine kinase domain (FLT3-TKD). Gilteritinib is a FLT3 inhibitor that inhibits both FLT3-ITD and FLT3-TKD. It was reported that differentiation of leukemic blasts accompanied by differentiation syndrome occurs in some patients treated with gilteritinib. However, information about the precise clinical course is limited, and appropriate management of differentiation syndrome has not been established. We report a case of relapsed AML with FLT3-ITD that was treated with gilteritinib. Analysis of the FLT3-ITD variant allele frequency (VAF) revealed that FLT3-ITD VAF was not decreased despite achievement of complete remission with incomplete hematologic recovery. Remarkable increases of monocytes and granulocytes accompanied by differentiation syndrome were observed at 6 months after the initiation of gilteritinib treatment. Intermittent chemotherapy with low-dose cytarabine and mitoxantrone was effective for reducing myelomonocytosis and resolving differentiation syndrome.The impact of the COVID-19 pandemic and lockdown may affect suicide risk and behavior. We compared suicide-related presentations during the national quarantine with pre-COVID data. This observational incidence study compared all suicide-related presentations at the University Hospital Reina Sofia emergency department (ED) in Cordoba, Spain, for the lockdown period from 15 March to 15 May 2020, with the same period in 2019. Descriptive and inferential analyses of case characteristics between 2019 and 2020 periods were conducted, and a multivariable logistic regression model developed. Results Despite a decrease in overall ED cases during the lockdown, the number of suicide-related presentations stayed the same and represented a significantly larger proportion of cases in comparison to the pre-COVID period (0.42 vs. 0.87%, in 2019 and 2020, respectively; p less then .001). The number presenting alone more than doubled during the COVID lockdown, increasing to 42.9% compared with 19.4% in 2019 (p = .002). An increase in presentations with a family history of suicide was also found.
