Disparities in early death and survival in children, adolescents, and young adults with acute promyelocytic leukemia in California.

BACKGROUND: Findings from clinical trials and population-based studies have differed with regard to whether mortality within 30 days of diagnosis (early death) of acute promyelocytic leukemia (APL) has decreased in the era of all-trans retinoic acid and anthracycline-based chemotherapy. METHODS: Using data from the California Cancer Registry, the authors investigated 7-day and 30-day mortality and survival in 772 patients who were aged birth to 39 years when they were diagnosed with APL during 1988 to 2011. Logistic regression and Cox proportional models were used to examine the association of early death and survival, respectively, with sociodemographic and clinical factors. RESULTS: The overall 30-day mortality decreased significantly over time, from 26% (1988-1995) to 14% (2004-2011) (P =.004). On multivariable analysis, the odds of 30-day mortality were 3 times as high during 1988 through 1995 than 2004 through 2011 (P =.001). However, 7-day mortality did not improve over time (P =.229). When patients who died within 7 days of diagnosis were excluded, the 30-day mortality during 1996 to 2011 was 3% to 8%, which is similar to levels reported in clinical trials. Higher early death and lower survival were associated with a lack of health insurance (1996-2011) (early death odds ratio, 2.67; P =.031) and Hispanic race/ethnicity (early death odds ratio, 2.13; P =.014). Early death was not found to be associated with age, sex, socioeconomic status, or hospital type. Black patients also experienced worse survival. CONCLUSIONS: The findings of the current study revealed a decreased 30-day mortality during the all-trans retinoic acid era, but 7-day mortality remained high. Efforts to achieve equal outcomes in young patients with APL should focus on improving access to effective treatment, mainly among uninsured patients and those of Hispanic and black race/ethnicity

Chitosan/nanocellulose electrospun fibers with enhanced antibacterial and antifungal activity for wound dressing applications

The combination of biodegradable fibers at nanoscale with plant-based extracts is attracting increasing attention to produce wound dressing systems. In this work, nanofibers based on chitosan (CS), poly(ethylene oxide) (PEO), cellulose nanocrystals (CNC) and acacia plant-based extract were developed by electrospinning. Firstly, the polymeric formulations and electrospinning parameters were optimized, resulting in nanofibers with average diameters of 80 nm. CNC were successfully introduced into the optimized CS/PEO blend and the membranes were characterized by FESEM, ATR-FTIR, TGA, XRD, WVTR and WCA. The CNC incorporation improved the nanofibers' physical integrity, morphology, diameters, water vapor transmission rate and thermal properties. After acacia introduction into the best CS/PEO/CNC system, the antibacterial effect was relatively maintained while the antifungal activity was enhanced for some fungi, demonstrating its great effect against a wide range of microorganisms, which is crucial to prevent or treat infections. All the developed systems exhibited absence of cytotoxicity in non-tumor cells, suggesting their biocompatibility. Finally, a continuous release of the acacia extract was observed for 24 h, showing its prolonged action, which contributes to the healing process while reduces the frequency of dressing's replacement. Overall, the developed nanofibers are very promising to act as localized drug delivery systems for wound care applications.The authors are thankful to TSSiPRO project, operation code NORTE01-0145-FEDER-000015. The authors are also grateful to FCT, Portugal for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020) and to 2C2T (UID/CTM/00264/2019). D. P. Ferreira thank the national funding by FCT through the individual scientific employment program-contract (CEECIND/02803/2017), S. M. Costa thank the FCT PhD Scholarship (SFRH/BD/147517/2019), and L. Barros and R. Calhelha thank the institutional scientific employment program-contract. This work has been supported by the Ministry of Education, Science and Technological Development of Republic of Serbia (451-03-68/2020-14/200007).CEECIND/02803/2017SFRH/BD/147517/2019info:eu-repo/semantics/publishedVersio

Specific Immunoassays for Placental Alkaline Phosphatase As a Tumor Marker

Human placental (hPLAP) and germ cell (PLAP-like) alkaline phosphatases are polymorphic and heat-stable enzymes. This study was designed to develop specific immunoassays for quantifying hPLAP and PLAP-like enzyme activity (EA) in sera of cancer patients, pregnant women, or smokers. Polyclonal sheep anti-hPLAP antibodies were purified by affinity chromatography with whole hPLAP protein (ICA-PLAP assay) or a synthetic peptide (aa 57–71) of hPLAP (ICA-PEP assay); the working range was 0.1–11 U/L and cutoff value was 0.2 U/L EA for nonsmokers. The intra- and interassay coefficients of variation were 3.7%–6.5% (ICA-PLAP assay) and 9.0%–9.9% (ICA-PEP assay). An insignificant cross-reactivity was noted for high levels of unheated intestinal alkaline phosphatase in ICA-PEP assay. A positive correlation between the regression of tumor size and EA was noted in a child with embryonal carcinoma. It can be concluded that ICA-PEP assay is more specific than ICA-PLAP, which is still useful to detect other PLAP/PLAP-like phenotypes

Second Primary Malignancy After Acute Promyelocytic Leukemia: a Population-Based Study

Acute promyelocytic leukemia (APL), is now highly curable with treatment approaches that include all-trans retinoic acid (ATRA). The high incidence of APL in the Hispanics suggests an association with genetic variants in this population. Information on second primary malignancies (SPMs) in patients with APL is limited. The Surveillance, Epidemiology, and End Results (SEER) database was used to interrogate whether the rate of SPMs in patients with APL was associated with ethnicity and/or ATRA treatment. Between 2000 and 2016, 116 cases of SPM were diagnosed among 4019 patients with APL. The mean age at diagnosis of primary APL was 53.9 years (±15.7 years), and the mean age at diagnosis of SPMs was 59.0 years (±14.5 years). Comparisons with 3774 APL survivors who did not develop SPMs revealed that age ≥40 years at diagnosis of APL (p < 0.001) and non-Hispanic white ethnicity (p = 0.025) were associated with SPMs in APL survivors. Salivary gland, liver, and soft tissue malignancies were significantly more common in patients with primary APL than in individuals with non-APL malignancies. A risk analysis comparing patients who had APL with patients who had non-APL AML suggests that SPMs after APL is associated with ATRA treatment. Therefore, patient follow-up after APL should focus on early diagnosis of SPMs

Corrigendum to ‘‘Silk-based biomaterials functionalized with fibronectin type II promotes cell adhesion” [Acta Biomater. 47 (2017) 50–59]

The authors regret that Telma C. Bernardo was inadvertently omitted in the author line-up. The correct authorship order should be as follows: Ana Margarida Pereira, Raul Machado, André da Costa, Artur Ribeiro, Telma C. Bernardo, Tony Collins, Andreia C. Gomes, Isabel B. Leonor, David L. Kaplan, Rui L. Reis, Margarida Casal. Telma C. Bernardo participated in recombinant 6mer+FNII production and purification. The authors regret the error and would like to apologize for any inconvenience caused.- (undefined

Rational development of liposomal hydrogels: A strategy for topical vaginal antiretroviral drug delivery in the context of HIV prevention

HIV/AIDS stands as a global burden, and vaginal microbicides constitute a promising strategy for topical pre-exposure prophylaxis. Preceding the development of a microbicide containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), in silico and in vitro studies were performed to evaluate the physicochemical characteristics of both drugs, and to study their biophysical impact in lipid model systems. Results from these pre-formulation studies defined hydrogels as adequate vehicles to incorporate TDF-loaded liposomes and FTC. After studying interactions with mucin, zwitterionic liposomes with a mean diameter of 134 ± 13 nm, an encapsulation TDF efficiency of approximately 84%, and a transition temperature of 41 °C were selected. The chosen liposomal formulation was non-cytotoxic to HEC-1-A and CaSki cells, and was able to favor TDF permeation across polysulfone membranes (Jss = 9.9 μg·cm−2·h−1). After the incorporation of TDF-loaded liposomes and FTC in carbomer hydrogels, the drug release profile was sustained over time, reaching around 60% for both drugs within 3–6 h, and best fitting the Weibull model. Moreover, liposomal hydrogels featured pseudoplastic profiles that were deemed suitable for topical application. Overall, the proposed liposomal hydrogels may constitute a promising formulation for the vaginal co-delivery of TDF/FTC.Funding for this work was provided by Fundação para a Ciência e Tecnologia (FCT) in the framework of the Strategic Funding UID/FIS/04650/2019 and in the ambit of the project POCI-01-0145-FEDER-032651 and PTDC/ NAN-MAT/326512017, co-financed by the European Regional Development Fund (ERDF), through COMPETE 2020, under Portugal 2020, and FCT I.P. This work was also supported by the strategic program UID/BIA/04050/2019 and project ERA-IB-2-6/0004/2014 funded by national Portuguese funds through FCT I.P. M. Lúcio thanks FCT and ERDF for doctoral position Ref. CTTI-150/18-CF(1) in the ambit of the project CONCERT (POCI-01-0145-FEDER-032651 and PTDC/NAN-MAT/326512017). This work was further supported by Institute for Research and Innovation in Health Sciences (UID/BIM/04293/2019), by Programa Gilead GÉNESE, Gilead Portugal (refs. PGG/046/2015 and PGG/002/2016), and by CEB (UID/BIO/04469/2019)

Association of the germline TP53 R337H mutation with breast cancer in southern Brazil

<p>Abstract</p> <p>Background</p> <p>The germline <it>TP53</it>-R337H mutation is strongly associated with pediatric adrenocortical tumors (ACT) in southern Brazil; it has low penetrance and limited tissue specificity in most families and therefore is not associated with Li-Fraumeni syndrome. However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context.</p> <p>Methods</p> <p>We conducted a case-control study to determine the prevalence of the R337H mutation by sequencing <it>TP</it>53 exon 10 in 123 women with breast cancer and 223 age- and sex-matched control subjects from southern Brazil. Fisher's test was used to compare the prevalence of the R337H.</p> <p>Results</p> <p>The R337H mutation was found in three patients but in none of the controls (p = 0.0442). Among the carriers, two had familial history of cancer meeting the Li-Fraumeni-like criteria. Remarkably, tumors in each of these three cases underwent loss of heterozygosity by eliminating the mutant <it>TP53 </it>allele rather than the wild-type allele. Polymorphisms were identified within the <it>TP53 </it>(R72P and Ins16) and <it>MDM2 </it>(SNP309) genes that may further diminish <it>TP53 </it>tumor suppressor activity.</p> <p>Conclusion</p> <p>These results demonstrate that the R337H mutation can significantly increase the risk of breast cancer in carriers, which likely depends on additional cooperating genetic factors. These findings are also important for understanding how low-penetrant mutant <it>TP53 </it>alleles can differentially influence tumor susceptibility.</p

Isosexual precocious pseudopuberty during mitotane treatment in a child with adrenocortical carcinoma:A case report

Background Mitotane is employed as adjuvant therapy in managing adrenocortical carcinoma in pediatric patients. While various adverse effects, such as estrogen-like manifestations, are well-documented in adults, there is limited knowledge regarding pediatric-specific toxicity. This report details an uncommon case of isosexual precocious pseudopuberty induced during childhood due to the estrogen-like effects of mitotane. Case report A 2.8-year-old female diagnosed with adrenocortical carcinoma (pT4 pN0 M0) underwent adjuvant treatment with mitotane and cytotoxic chemotherapy following incomplete resection (tumor stage III). Approximately eight months into mitotane treatment, she exhibited signs of puberty (Tanner stage 2), including progressive breast development, uterine enlargement, vaginal discharge, and an advancement of bone age by nearly two years. Gonadotrophin-dependent puberty and endogenous estrogen production were ruled out. The precocious pseudopuberty was attributed to previously reported estrogen-like effects of mitotane therapy. Subsequent administration of the aromatase inhibitor anastrozole in combination with mitotane led to a reduction in clinical signs of puberty. Conclusion Monitoring for estrogen-like effects of mitotane is crucial, particularly in pre-pubertal children, to avert potentially irreversible changes associated with precocious pseudopuberty. Aromatase inhibitors may serve as a prompt therapeutic option, enabling the continuation of mitotane treatment

Atlantic mammal traits: a dataset of morphological traits of mammals in the atlantic forest of south America

Measures of traits are the basis of functional biological diversity. Numerous works consider mean species-level measures of traits while ignoring individual variance within species. However, there is a large amount of variation within species and it is increasingly apparent that it is important to consider trait variation not only between species, but also within species. Mammals are an interesting group for investigating trait-based approaches because they play diverse and important ecological functions (e.g., pollination, seed dispersal, predation, grazing) that are correlated with functional traits. Here we compile a data set comprising morphological and life history information of 279 mammal species from 39,850 individuals of 388 populations ranging from −5.83 to −29.75 decimal degrees of latitude and −34.82 to −56.73 decimal degrees of longitude in the Atlantic forest of South America. We present trait information from 16,840 individuals of 181 species of non-volant mammals (Rodentia, Didelphimorphia, Carnivora, Primates, Cingulata, Artiodactyla, Pilosa, Lagomorpha, Perissodactyla) and from 23,010 individuals of 98 species of volant mammals (Chiroptera). The traits reported include body mass, age, sex, reproductive stage, as well as the geographic coordinates of sampling for all taxa. Moreover, we gathered information on forearm length for bats and body length and tail length for rodents and marsupials. No copyright restrictions are associated with the use of this data set. Please cite this data paper when the data are used in publications. We also request that researchers and teachers inform us of how they are using the data.Fil: Gonçalves, Fernando. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Bovendorp, Ricardo S.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Beca, Gabrielle. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Bello, Carolina. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Costa Pereira, Raul. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Muylaert, Renata L.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Rodarte, Raisa R.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Villar, Nacho. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Souza, Rafael. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Graipel, Maurício E.. Universidade Federal de Santa Catarina; BrasilFil: Cherem, Jorge J.. Caipora Cooperativa, Florianopolis; BrasilFil: Faria, Deborah. Universidade Estadual de Santa Cruz; BrasilFil: Baumgarten, Julio. Universidade Estadual de Santa Cruz; BrasilFil: Alvarez, Martín R.. Universidade Estadual de Santa Cruz; BrasilFil: Vieira, Emerson M.. Universidade do Brasília; BrasilFil: Cáceres, Nilton. Universidade Federal de Santa María. Santa María; BrasilFil: Pardini, Renata. Universidade de Sao Paulo; BrasilFil: Leite, Yuri L. R.. Universidade Federal do Espírito Santo; BrasilFil: Costa, Leonora Pires. Universidade Federal do Espírito Santo; BrasilFil: Mello, Marco Aurelio Ribeiro. Universidade Federal de Minas Gerais; BrasilFil: Fischer, Erich. Universidade Federal do Mato Grosso do Sul; BrasilFil: Passos, Fernando C.. Universidade Federal do Paraná; BrasilFil: Varzinczak, Luiz H.. Universidade Federal do Paraná; BrasilFil: Prevedello, Jayme A.. Universidade do Estado de Rio do Janeiro; BrasilFil: Cruz-Neto, Ariovaldo P.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Carvalho, Fernando. Universidade do Extremo Sul Catarinense; BrasilFil: Reis Percequillo, Alexandre. Universidade de Sao Paulo; BrasilFil: Paviolo, Agustin Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú; ArgentinaFil: Duarte, José M. B.. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil. Fundación Oswaldo Cruz; BrasilFil: Bernard, Enrico. Universidade Federal de Pernambuco; BrasilFil: Agostini, Ilaria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú; ArgentinaFil: Lamattina, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Ministerio de Salud de la Nación; ArgentinaFil: Vanderhoeven, Ezequiel Andres. Ministerio de Salud de la Nación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentin