Experimental estimation of quantum discord for polarization qubit and the use of fidelity to assess quantum correlations

We address the experimental determination of entropic quantum discord for systems made of a pair of polarization qubits. We compare results from full and partial tomography and found that the two determinations are statistically compatible, with partial tomography leading to a smaller value of discord for depolarized states. Despite the fact that our states are well described, in terms of fidelity, by families of depolarized or phase-damped states, their entropic discord may be largely different from that predicted for these classes of states, such that no reliable estimation procedure beyond tomography may be effectively implemented. Our results, together with the lack of an analytic formula for the entropic discord of a generic two-qubit state, demonstrate that the estimation of quantum discord is an intrinsically noisy procedure. Besides, we question the use of fidelity as a figure of merit to assess quantum correlations

INITIAL IMPACT OF THE COVID-19 PANDEMIC ON THE CARE PROFILE FOR CRITICALLY-ILL PATIENTS ON HEMODIALYSIS

Objective: to compare the care profile for critically-ill patients on hemodialysis before and during the COVID-19 pandemic.Method: an observational study carried out in a hospital from São Paulo, Brazil. The participants were critically-ill patients on hemodialysis hospitalized in 2019 and 2020. The data were collected from documents of hemodialysis sessions and from medical records. Chi-square, Mann-Whitney, Shapiro-Wilk and Fisher's Exact tests were used for comparisons (p<0.05).Results: a total of 212 sessions were performed with 50 patients in 2019 and 873 sessions with 171 patients in 2020. In 2019, the patients were referred to intensive care and hemodialysis after 4.62 ± 6.38 and 17.26 ± 24.53 days, respectively, and in 2020 these periods corresponded to 2.21 ± 3.63 and 10.24 ± 11.99 days. There were more deaths in 2020 (p=0.01) and among patients with COVID-19 (p=0.014).Conclusion: more hemodialysis sessions were observed in 2020 when compared to pre-pandemic times, an unknown situation in the first months of the pandemic

Phleboviruses detection in Phlebotomus perniciosus from a human leishmaniasis focus in South-West Madrid region, Spain

Phlebotomus-borne (PhB-) viruses are distributed in large areas of the Old World and are widespread throughout the Mediterranean basin, where recent investigations have indicated that virus diversity is higher than initially suspected. Some of these viruses are causes of meningitis, encephalitis and febrile illnesses. In order to monitor the viral presence and the infection rate of PhB-viruses in a recently identified and well characterized human zoonotic leishmaniasis focus in southwestern Madrid, Spain, a sand fly collection was carried out. Methods Sand fly insects were collected in four stations using CDC light traps during 2012–2013 summer seasons. Screening for Phlebovirus presence both via isolation on Vero cells and via polymerase chain reaction (PCR), using degenerated primers targeting a portion of the L segment, was performed. The serological identity and phylogenetic relationships on the three genomic segments of the viral isolates were carried out. Results Six viral isolates belonging to different serological complexes of the genus Phlebovirus were obtained from fifty pools on a total of 963 P. perniciosus (202 females). Phylogenetic analysis and serological assays allowed the identification of two isolates of Toscana virus (TOSV) B genotype, three isolates strongly related to Italian Arbia virus (ARBV), and one isolate of a novel putative Phlebovirus related to the recently characterized Arrabida virus in South Portugal, tentatively named Arrabida-like virus. Positive male sand fly pools suggested that transovarial or venereal transmission could occur under natural conditions. Conclusions Our findings highlighted the presence of different Phlebovirus species in the South-West area of the Madrid Autonomous Community where an outbreak of cutaneous and visceral human leishmaniasis has been recently described. The evidence of viral species never identified before in Spain, as ARBV and Arrabida-like virus, and TOSV B genotype focus stability was demonstrated. Environmental aspects such as climate change, growing urbanization, socio-economic development could have contributed to the genesis of this wide ecological niche of PhB-viruses and Leishmania spp. The potential role of vertebrates as reservoir for the phleboviruses identified and the possibility of Phleboviruses-Leishmania co-infection in the same sand fly should be assessed. Furthermore the PhB-viruses impact on human health should be implemented.This study was funded by EU grant FP7-261504 EDENext and is catalogued by the EDENext Steering Committee as EDENext432 (http://www.edenext.eu). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission.S

130 purification of large scale mrna encoding zfn nucleases by dhplc technology

A novel strategy of targeted gene correction of the interleukin-2 receptor common gamma chain (IL2RG) gene for the treatment of X-linked Severe Combined Immunodeficiency (SCID-X1) is achieved by the combination of a pair of IL2RG-specific Zinc Finger Nucleases (ZFN) and the correct-gene template DNA delivered by integration-defective lentiviral vector (IDLV).The transient expression of the ZFN pair targeting the disease-causing gene is obtained by the electroporation of the two corresponding mRNAs, produced by in vitro transcription starting from plasmid DNA template. A major limitation of the mRNA transcribed in vitro is the presence of residual contaminants such as short RNAs and double stranded (ds)RNAs that may affect the function and spectrophotometric quantification of the product hampering therefore the delivery of high quality and precise amount of mRNA to target cells. Moreover, dsRNA contaminants represent a possible risk in terms of immunogenicity of the product, leading to activation of unwanted innate immune response with consequent reduction/abrogation of mRNA translation as well as potential alteration of the properties of the transfected cells. To improve nuclease expression while decreasing cellular innate response to mRNA transfection we combined different strategies: (i) inclusion of UTRs and polyA tails in the DNA template used for mRNA production; (ii) use of modified nucleotides during mRNA production and (iii) purification of the mRNAs by dHPLC with a reverse phase column made of non-porous matrix consisting of polystyrene-divinylbenzene copolymer beads alkylated with C-18 chains (Transgenomic, LTD.). In particular, the purification of in vitro transcribed mRNAs by means of dHPLC has been shown to strongly improve the translation of mRNA and significantly reduce the contaminant presence thus preventing innate immunity and eventually increasing modified cells persistence in vivo. We have developed feasible and reproducible, small and large scale mRNA production and downstream purification processes of the ZFN pairs obtaining accurate RNA quantification and reduced risk of immunogenicity. The full process achieved a 60% yield, loading with a 500µg RNA for each run with a single clean chromatographic peak. Furthermore, the level of residual organic solvent (i.e. Acetonitrile) used in the purification process is compatible with that applicable into clinic. The highly translatable non-immunogenic dHPLC-purified mRNA can be delivered without toxicity and represents a powerful and safe tool for the application of gene therapy protocols

Impacto da pandemia pela COVID-19 no perfil de pacientes críticos atendidos por um serviço de hemodiálise

Introduction&nbsp;and objective:&nbsp;Critically ill patients with COVID-19 often progress to acute kidney injury and need for hemodialysis. The aim of this study was to compare the care profile of critically ill patients undergoing renal replacement therapy before and during the COVID-19 pandemic. Methods:&nbsp;Observational study carried out at a university hospital in the city of São Paulo, Brazil. Critical patients undergoing hemodialysis from April to June 2019 and April to June 2020 participated in the study. Data were collected from hemodialysis care documents and electronic medical records. The Chi-square, Mann-Whitney, Shapiro-Wilk, Fisher's exact test were used (5% significance). Results: 212 patients participated, 50 in 2019 and 171 in 2020. In 2019, 30.0% of patients were hospitalized due to acute renal changes, 90.0% had increased entry creatinine, were referred to intensive care after 4.62± 6.38 days and started hemodialysis after 17.26±24.53 days. In 2020, 66.7% were hospitalized for COVID-19, 77.7% had increased entry creatinine, were referred to intensive care after 2.21±3.63 days and started hemodialysis after 10.24±11.99 days . 212 hemodialysis sessions were performed in 2019 and 873 in 2020. There were more deaths in 2020 (p=0.01) and patients with COVID-19 (p=0.014) and hemodynamic instability (p=0.016) were the most affected. Conclusion:&nbsp;In 2020, there was an increase of 3.42 times in the number of critical patients on hemodialysis and an increase of 4.11 times in the number of sessions compared to the year 2019.Introducción y objetivo: Los pacientes críticamente enfermos con COVID-19 a menudo progresan a una lesión renal aguda y necesitan hemodiálisis. El objetivo de este estudio fue comparar el perfil de atención de los pacientes críticamente enfermos sometidos a terapia de reemplazo renal antes y durante la pandemia de COVID-19.Métodos: estudio observacional realizado en un hospital universitario de la ciudad de São Paulo, Brasil. En el estudio participaron pacientes críticos sometidos a hemodiálisis de abril a junio de 2019 y de abril a junio de 2020. Los datos se obtuvieron de documentos de atención de hemodiálisis y registros médicos electrónicos. Se utilizó la prueba de Chi-cuadrado, Mann-Whitney, Shapiro-Wilk, exacta de Fisher (significancia del 5%).Resultados: participaron 221 pacientes, 50 en 2019 y 171 en 2020. En 2019, el 30,0% de los pacientes fueron hospitalizados por alteraciones renales agudas, el 90,0% presentó aumento de creatinina de entrada, fueron remitidos a cuidados intensivos a los 4,62 ± 6,38 días e iniciaron hemodiálisis posteriormente. 17,26 ± 24,53 días. En 2020, el 66,7% fueron hospitalizados por COVID-19, el 77,7% presentó aumento de creatinina de entrada, fueron remitidos a cuidados intensivos a los 2,21 ± 3,63 días e iniciaron hemodiálisis a los 10,24 ± 11,99 días. Se realizaron 212 sesiones de hemodiálisis en 2019 y 873 en 2020. Hubo más muertes en 2020 (p = 0.01) y los pacientes con COVID-19 (p = 0.014) e inestabilidad hemodinámica (p = 0.016) fueron los más afectados.Conclusión: En 2020, hubo un aumento de 3,42 veces en el número de pacientes críticos en hemodiálisis y un aumento de 4,11 veces en el número de sesiones respecto al año 2019.Introdução e objetivo:&nbsp;Frequentemente os pacientes críticos com COVID-19 evoluem para lesão renal aguda e necessidade de hemodiálise. O objetivo deste estudo foi comparar o perfil de atendimento aos pacientes críticos submetidos a terapia de substituição renal antes e durante a pandemia pela COVID-19. Métodos:&nbsp;Estudo observacional realizado em um hospital universitário da cidade de São Paulo, Brasil. Participaram do estudo pacientes&nbsp;críticos em hemodiálise de abril a junho de 2019 e abril a junho de 2020. Os dados foram coletados a partir de documentos de atendimento de hemodiálise e prontuário eletrônico. Foram utilizados os testes de&nbsp;Qui-quadrado, Mann-Whitney, Shapiro-Wilk, Teste Exato de Fisher,&nbsp;(significância de 5%). Resultados: Participaram 221 pacientes, sendo 50 em 2019 e 171 em 2020. Em 2019, 30,0% dos pacientes internaram por alterações renais agudas, 90,0% apresentaram creatinina de entrada aumentada, foram encaminhados para terapia intensiva após 4,62±6,38 dias e iniciaram hemodiálise após 17,26±24,53 dias. Em 2020, 66,7% internaram por COVID-19, 77,7% tiveram creatinina de entrada aumentada, foram encaminhados para terapia intensiva após 2,21±3,63 dias e iniciaram a hemodiálise após 10,24±11,99 dias. Foram realizadas 212 sessões de hemodiálise em 2019 e 873 em 2020. Houve mais óbitos em 2020 (p=0,01) e os pacientes com COVID-19 (p=0,014) e instabilidade hemodinâmica (p=0,016) foram os mais acometidos. Conclusão:&nbsp;Em 2020, foi observado aumento de 3,42 vezes no número de pacientes críticos em hemodiálise e aumento de 4,11 vezes no número de sessões quanto comparado ao ano de 2019

The emerging role of cancer nanotechnology in the panorama of sarcoma

In the field of nanomedicine a multitude of nanovectors have been developed for cancer application. In this regard, a less exploited target is represented by connective tissue. Sarcoma lesions encompass a wide range of rare entities of mesenchymal origin affecting connective tissues. The extraordinary diversity and rarity of these mesenchymal tumors is reflected in their classification, grading and management which are still challenging. Although they include more than 70 histologic subtypes, the first line-treatment for advanced and metastatic sarcoma has remained unchanged in the last fifty years, excluding specific histotypes in which targeted therapy has emerged. The role of chemotherapy has not been completely elucidated and the outcomes are still very limited. At the beginning of the century, nano-sized particles clinically approved for other solid lesions were tested in these neoplasms but the results were anecdotal and the clinical benefit was not substantial. Recently, a new nanosystem formulation NBTXR3 for the treatment of sarcoma has landed in a phase 2-3 trial. The preliminary results are encouraging and could open new avenues for research in nanotechnology. This review provides an update on the recent advancements in the field of nanomedicine for sarcoma. In this regard, preclinical evidence especially focusing on the development of smart materials and drug delivery systems will be summarized. Moreover, the sarcoma patient management exploiting nanotechnology products will be summed up. Finally, an overlook on future perspectives will be provided

IMPACTO INICIAL DA PANDEMIA PELA COVID-19 NO PERFIL DE ATENDIMENTO AOS PACIENTES CRÍTICOS EM HEMODIÁLISE

Objetivo: comparar o perfil de atendimento aos pacientes críticos em hemodiálise antes e durante a pandemia pela COVID-19.Método: estudo observacional realizado em um hospital de São Paulo - Brasil. Participaram pacientes críticos em hemodiálise internados em 2019 e 2020. Os dados foram coletados de documentos das sessões de hemodiálise e prontuários. Foram utilizados os testes de Qui-quadrado, Mann-Whitney, Shapiro-Wilk e Exato de Fisher para as comparações (p<0,05).Resultados: foram realizadas 212 sessões em 50 pacientes em 2019 e 873 sessões em 171 pacientes em 2020. Em 2019 os pacientes foram encaminhados para terapia intensiva e hemodiálise após 4,62±6,38 e 17,26±24,53 dias, respectivamente, e em 2020 esses períodos foram de 2,21±3,63 e 10,24±11,99 dias. Houve mais óbitos em 2020 (p=0,01) e entre os pacientes com COVID-19 (p=0,014).Conclusão: foi observado um maior número de hemodiálises em 2020 quando comparado ao quadro pré-pandêmico, situação desconhecida nos primeiros meses da pandemia

IMPACTO INICIAL DE LA PANDEMIA DE COVID-19 EN EL PERFIL DE ATENCIÓN DE LOS PACIENTES CRÍTICOS EN HEMODIÁLISIS

Objetivo: comparar el perfil de atención de los pacientes críticos en hemodiálisis antes y durante la pandemia de COVID-19.Método: estudio observacional realizado en un hospital de San Pablo, Brasil. Participaron pacientes críticos en hemodiálisis hospitalizados en 2019 y 2020. Los datos se recolectaron de documentos de sesiones de hemodiálisis e historias clínicas. Para las comparaciones se utilizaron las pruebas de chi-cuadrado, Mann-Whitney, Shapiro-Wilk y exacta de Fisher (p<0,05).Resultados: se realizaron 212 sesiones en 50 pacientes en 2019 y 873 sesiones en 171 pacientes en 2020. En 2019 los pacientes fueron derivados a cuidados intensivos y hemodiálisis después de 4,62 ± 6,38 y 17,26 ± 24,53 días, respectivamente, y en 2020 los períodos fueron de 2,21 ± 3,63 y 10,24 ± 11,99 días. Hubo más muertes en 2020 (p=0,01) y de pacientes con COVID-19 (p=0,014).Conclusión: se observó un mayor número de hemodiálisis en 2020 que ante de la prepandemia, hecho que se desconocía durante los primeros meses de la pandemia

Sorcin is an early marker of neurodegeneration, Ca2+ dysregulation and endoplasmic reticulum stress associated to neurodegenerative diseases

Dysregulation of calcium signaling is emerging as a key feature in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), and targeting this process may be therapeutically beneficial. Under this perspective, it is important to study proteins that regulate calcium homeostasis in the cell. Sorcin is one of the most expressed calcium-binding proteins in the human brain; its overexpression increases endoplasmic reticulum (ER) calcium concentration and decreases ER stress in the heart and in other cellular types. Sorcin has been hypothesized to be involved in neurodegenerative diseases, since it may counteract the increased cytosolic calcium levels associated with neurodegeneration. In the present work, we show that Sorcin expression levels are strongly increased in cellular, animal, and human models of AD, PD, and HD, vs. normal cells. Sorcin partially colocalizes with RyRs in neurons and microglia cells; functional experiments with microsomes containing high amounts of RyR2 and RyR3, respectively, show that Sorcin is able to regulate these ER calcium channels. The molecular basis of the interaction of Sorcin with RyR2 and RyR3 is demonstrated by SPR. Sorcin also interacts with other ER proteins as SERCA2 and Sigma-1 receptor in a calcium-dependent fashion. We also show that Sorcin regulates ER calcium transients: Sorcin increases the velocity of ER calcium uptake (increasing SERCA activity). The data presented here demonstrate that Sorcin may represent both a novel early marker of neurodegenerative diseases and a response to cellular stress dependent on neurodegeneration