The expansion and intensification seen in the production of açaí, a fruit that typically grows in the Amazon, can have undesirable and serious socio-environmental consequences. Based on the premise ...that financialization in the agrifood sector accelerates processes that destroy the environment, an investigation is carried out into the claim that the supply chain regarding açaí is in the process of being financialized. Due to the absence of literature concerning this subject, this article serves as an exploratory case study with a theoretical base. As a result, primary information was collected as much from field visits as from official sources. These field visits produced semi-structured interviews (both in-person and virtual) and informal conversations with some of the actors involved in the açaí production chain. This article argues that the financialization of açaí is still in its early stages. This is primarily due to the involvement of large, financialized corporations, state support for expanding production, and the development of new products and agro-industrial technology. A ampliação e a intensificação da produção de açaí, um fruto típico da Amazônia, tem gerado consequências socioambientais indesejáveis. Partindo do pressuposto de que a financeirização agroalimentar acelera processos de destruição ecológica, buscamos investigar se a cadeia do açaí está financeirizada. Devido à ausência de literatura a respeito deste tema, realizamos um estudo de caso exploratório e teoricamente orientado. Coletamos informações primárias tanto em fontes oficiais quanto em visitas de campo, por meio de entrevistas semiestruturadas (presenciais e virtuais) e de diálogos informais com alguns dos atores da cadeia produtiva do açaí. Concluímos que a financeirização do açaí está em estágio inicial, principalmente devido à entrada de grandes corporações financeirizadas e ao apoio estatal para a ampliação da produção, para o desenvolvimento de tecnologias agroindustriais e de novos produtos.
A new electrode based on glassy carbon modified with an alginate film cross-linked with glutaraldehyde containing immobilized carbon black particles was successfully developed and applied for the ...determination of paraquat (PQ), a herbicide widely used for broadleaf weed control. Different polysaccharides (alginate, cellulose, pectin, starch, and chitosan) were investigated for the immobilization process, and alginate presented the highest chemical modifier potential for PQ determination. Additionally, the influence of chemical cross-linking agents (glutaraldehyde and epichlorohydrin) on the morphology, electrochemical response, and film stability was investigated. All experimental conditions were optimized, including the supporting electrolyte conditions (composition, pH, and concentration) and square wave voltammetry technical parameters. Under the optimized experimental conditions, the PQ analytical curve was linear from 0.4 to 2.0 mg L
-1
and the limits of detection and quantification were 0.06 and 0.19 mg L
-1
, respectively. The proposed electrode is easy to obtain, stable, selective, sensitive, and low cost and was successfully applied for PQ determination in environmental and beverage samples.
Graphical abstract
Gain of chromosome 1q (+1q) is one of the most common recurrent cytogenetic abnormalities in multiple myeloma (MM), occurring in approximately 40% of newly diagnosed cases. Although it is often ...considered a poor prognostic marker in MM, +1q has not been uniformly adopted as a high-risk cytogenetic abnormality in guidelines. Controversy exists regarding the importance of copy number, as well as whether +1q is itself a driver of poor outcomes or merely a common passenger genetic abnormality in biologically unstable disease. Although the identification of a clear pathogenic mechanism from +1q remains elusive, many genes at the 1q21 locus have been proposed to cause early progression and resistance to anti-myeloma therapy. The plethora of potential drivers suggests that +1q is not only a causative factor or poor outcomes in MM but may be targetable and/or predictive of response to novel therapies. This review will summarize our current understanding of the pathogenesis of +1q in plasma cell neoplasms, the impact of 1q copy number, identify potential genetic drivers of poor outcomes within this subset, and attempt to clarify its clinical significance and implications for the management of patients with multiple myeloma.
Summary Background High-dose dexamethasone is a mainstay of therapy for multiple myeloma. We studied whether low-dose dexamethasone in combination with lenalidomide is non-inferior to and has lower ...toxicity than high-dose dexamethasone plus lenalidomide. Methods Patients with untreated symptomatic myeloma were randomly assigned in this open-label non-inferiority trial to lenalidomide 25 mg on days 1–21 plus dexamethasone 40 mg on days 1–4, 9–12, and 17–20 of a 28-day cycle (high dose), or lenalidomide given on the same schedule with dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle (low dose). After four cycles, patients could discontinue therapy to pursue stem-cell transplantation or continue treatment until disease progression. The primary endpoint was response rate after four cycles assessed with European Group for Blood and Bone Marrow Transplant criteria. The non-inferiority margin was an absolute difference of 15% in response rate. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00098475. Findings 445 patients were randomly assigned: 223 to high-dose and 222 to low-dose regimens. 169 (79%) of 214 patients receiving high-dose therapy and 142 (68%) of 205 patients on low-dose therapy had complete or partial response within four cycles (odds ratio 1·75, 80% CI 1·30–2·32; p=0·008). However, at the second interim analysis at 1 year, overall survival was 96% (95% CI 94–99) in the low-dose dexamethasone group compared with 87% (82–92) in the high-dose group (p=0·0002). As a result, the trial was stopped and patients on high-dose therapy were crossed over to low-dose therapy. 117 patients (52%) on the high-dose regimen had grade three or worse toxic effects in the first 4 months, compared with 76 (35%) of the 220 on the low-dose regimen for whom toxicity data were available (p=0·0001), 12 of 222 on high dose and one of 220 on low-dose dexamethasone died in the first 4 months (p=0·003). The three most common grade three or higher toxicities were deep-vein thrombosis, 57 (26%) of 223 versus 27 (12%) of 220 (p=0·0003); infections including pneumonia, 35 (16%) of 223 versus 20 (9%) of 220 (p=0·04), and fatigue 33 (15%) of 223 versus 20 (9%) of 220 (p=0·08), respectively. Interpretation Lenalidomide plus low-dose dexamethasone is associated with better short-term overall survival and with lower toxicity than lenalidomide plus high-dose dexamethasone in patients with newly diagnosed myeloma. Funding National Cancer Institute, Rockville, MD, USA.
The growing demand for sugar-free confectionery products with fruit added motivated the study of a dietary model system (chewy candy) to be the basis for the incorporation of a tropical Brazilian ...fruit (açai – Euterpe oleracea Mart.) with outstanding sensorial properties. The effect of the polyols maltitol, isomalt, xylitol and erythritol was evaluated on the water activity and instrumental texture of the dietary model systems through a simplex lattice mixture design. The trial with the best performance was chosen to incorporate a spray-dried açai powder and was compared to a reference açai chewy candy containing sucrose by sensory analysis. The sucrose replacement by isomalt and erythritol resulted in a soft texture (hardness of 4.08 N), proper water activity (0.43) and stable dietary system concerning the maintenance of shape. The addition of spray-dried açai powder (10.4 g/100 g, in dry basis) at this system enabled to explore the flavor and color potential of the fruit and to eliminate the addition of vegetable fat generally used at the conventional formulation. The sensory tests indicated that the no-added sucrose açai chewy candy was acceptable for all the evaluated attributes and approved regarding purchase intent, presenting better results than the containing-sucrose açai chewy candy.
•Maltitol, isomalt, xylitol and erythritol were used to produce chewy candies (CC).•CC based on isomalt and erythritol showed proper texture, aw and shape stability.•Spray-dried açai powder was applied to no-added sucrose and containing-sucrose CC.•Açai provided adequate fat content, natural color/flavor, good acceptability to CC.
The precise molecular mechanism of action and targets through which thalidomide and related immunomodulatory drugs (IMiDs) exert their antitumor effects remains unclear. We investigated the role of ...cereblon (CRBN), a primary teratogenic target of thalidomide, in the antimyeloma activity of IMiDs. CRBN depletion is initially cytotoxic to human myeloma cells, but surviving cells with stable CRBN depletion become highly resistant to both lenalidomide and pomalidomide, but not to the unrelated drugs bortezomib, dexamethasone, and melphalan. Acquired deletion of CRBN was found to be the primary genetic event differentiating isogenic MM1.S cell lines cultured to be sensitive or resistant to lenalidomide and pomalidomide. Gene expression changes induced by lenalidomide were dramatically suppressed in the presence of CRBN depletion, further demonstrating that CRBN is required for lenalidomide activity. Downstream targets of CRBN include interferon regulatory factor 4 (IRF4) previously reported to also be a target of lenalidomide. Patients exposed to, and putatively resistant to, lenalidomide had lower CRBN levels in paired samples before and after therapy. In summary, CRBN is an essential requirement for IMiD activity and a possible biomarker for the clinical assessment of antimyeloma efficacy.
Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma confined to the central nervous system. Whether there is a PCNSL-specific genomic signature and, if so, how it ...differs from systemic diffuse large B-cell lymphoma (DLBCL) is uncertain.
We performed a comprehensive genomic study of tumor samples from 19 immunocompetent PCNSL patients. Testing comprised array-comparative genomic hybridization and whole exome sequencing.
Biallelic inactivation of TOX and PRKCD was recurrently found in PCNSL but not in systemic DLBCL, suggesting a specific role in PCNSL pathogenesis. In addition, we found a high prevalence of MYD88 mutations (79%) and CDKN2A biallelic loss (60%). Several genes recurrently affected in PCNSL were common with systemic DLBCL, including loss of TNFAIP3, PRDM1, GNA13, TMEM30A, TBL1XR1, B2M, CD58, activating mutations of CD79B, CARD11, and translocations IgH-BCL6. Overall, B-cell receptor/Toll-like receptor/NF-κB pathways were altered in >90% of PNCSL, highlighting its value for targeted therapeutic approaches. Furthermore, integrated analysis showed enrichment of pathways associated with immune response, proliferation, apoptosis, and lymphocyte differentiation.
In summary, genome-wide analysis uncovered novel recurrent alterations, including TOX and PRKCD, helping to differentiate PCNSL from systemic DLBCL and related lymphomas.
The longitudinal evolution of a myeloma genome from diagnosis to plasma cell leukemia has not previously been reported. We used whole-genome sequencing (WGS) on 4 purified tumor samples and patient ...germline DNA drawn over a 5-year period in a t(4;14) multiple myeloma patient. Tumor samples were acquired at diagnosis, first relapse, second relapse, and end-stage secondary plasma cell leukemia (sPCL). In addition to the t(4;14), all tumor time points also shared 10 common single-nucleotide variants (SNVs) on WGS comprising shared initiating events. Interestingly, we observed genomic sequence variants that waxed and waned with time in progressive tumors, suggesting the presence of multiple independent, yet related, clones at diagnosis that rose and fell in dominance. Five newly acquired SNVs, including truncating mutations of RB1 and ZKSCAN3, were observed only in the final sPCL sample suggesting leukemic transformation events. This longitudinal WGS characterization of the natural history of a high-risk myeloma patient demonstrated tumor heterogeneity at diagnosis with shifting dominance of tumor clones over time and has also identified potential mutations contributing to myelomagenesis as well as transformation from myeloma to overt extramedullary disease such as sPCL.
For patients with multiple myeloma (MM), each additional line of therapy (LOT) is associated with lower response rates, shorter treatment duration and treatment-free intervals, and increased rates of ...toxicities and comorbidities. Here, we examine frontline treatment patterns, and attrition rates by LOT among newly diagnosed MM (NDMM) patients in the United States who were eligible or ineligible for autologous stem cell transplant (ASCT).
Data were identified from three US patient-level databases collectively covering the period January 2000 to September 2018. Patients had an index diagnosis of MM on or after January 1, 2007, medical and prescription insurance coverage at diagnosis, a 1-year look-back period prior to the index diagnosis, no prior malignancies in the 1-year period before index diagnosis, and had received ≥1 LOT.
Among patients who did not receive ASCT (non-transplant; n = 22,062), 12,557 (57%) received only 1 LOT and 9505 (43%) received > 1 LOT. Patients receiving only 1 LOT were significantly older, had higher mean Charlson Comorbidity Index (CCI) scores, and higher incidences of comorbidities. Among the 2763 patients receiving ASCT, 2184 received > 1 LOT, and 579 (21%) received only 1 LOT (ie, ASCT was the last treatment). 1682 (61%) patients received induction therapy as frontline treatment, of whom 187 (11%) also received consolidation therapy. The latter group was younger than those who received only induction therapy, had lower mean CCI scores, and comparable or lower incidences of selected comorbidities. The most common frontline therapy for non-transplant and transplant-eligible patients was bortezomib/dexamethasone and bortezomib/lenalidomide/dexamethasone, respectively. Attrition rates across all LOTs were high for non-transplant patients (range, 43-57%) and transplant patients (range, 21-37%). Treatment duration decreased by LOT for non-transplant patients and was consistent across LOTs for transplant patients.
In this analysis, a substantial proportion of patients with NDMM who received frontline therapy did not appear to receive a subsequent LOT. These high attrition rates underscore the need to use the most optimal treatment regimens upfront rather than reserving them for later LOTs in which the clinical benefit may decrease.
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