Chemical and biological evaluation of rejects from the wood industry.

Este estudo visa a caracterização química e a avaliação da atividade antimicrobiana de extratos obtidos a partir de rejeitos resultantes do beneficiamento de madeiras nobres comercializadas no Paraná: Peroba-Rosa (Aspidosperma sp.), Roxinho (Peltogyne sp.), Jatobá (Hymenaea sp.), Curupixá (Micropholis sp.), Itaúba (Mezilaurus sp.), Cedrilho (Erisma sp.) e Imbúia-do-Norte (Licaria sp.), cujas identificações botânicas basearam-se em estudos anatômicos. Os extratos foram preparados com diversos solventes, analisados por CCD e espectrometria UV/VIS, testando-se contra: Proteus mirabilis ATCC15290, Escherichia coli ATCC25922, Enterobacter aerogenes ATCC13048, Staphylococcus aureus ATCC25923, Micrococcus luteus ATCC9341, Klebsiella pneumoniae ATCC13883, Pseudomonas aeroginosa ATCC27853, e Staphylococcus aureus, Streptococcus mutans e Bacillus cereus isolados da clínica. O extrato etanólico de Peroba-Rosa, contendo alcalóides, apresentou atividade contra P. mirabilis. Os extratos metanólicos do Jatobá, Itaúba e Imbúia, contendo fenóis, e o extrato de Roxinho obtido com acetato de etila contendo fenóis e terpenóides, foram ativos contra K. pneumoniae, M. luteus, E. coli, S. aureus e P. mirabilis. Nenhum dos extratos foi ativo contra P. aeroginosa, S. mutans e E. aerogenes

HLA-G 3'UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment

An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host's immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3'UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3'UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3'UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3'UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3'UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38-0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26-0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19-5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16-6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3'UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G

Renormalization Group Flow in Scalar-Tensor Theories. II

We study the UV behaviour of actions including integer powers of scalar curvature and even powers of scalar fields with Functional Renormalization Group techniques. We find UV fixed points where the gravitational couplings have non-trivial values while the matter ones are Gaussian. We prove several properties of the linearized flow at such a fixed point in arbitrary dimensions in the one-loop approximation and find recursive relations among the critical exponents. We illustrate these results in explicit calculations in $d=4$ for actions including up to four powers of scalar curvature and two powers of the scalar field. In this setting we notice that the same recursive properties among the critical exponents, which were proven at one-loop order, still hold, in such a way that the UV critical surface is found to be five dimensional. We then search for the same type of fixed point in a scalar theory with minimal coupling to gravity in $d=4$ including up to eight powers of scalar curvature. Assuming that the recursive properties of the critical exponents still hold, one would conclude that the UV critical surface of these theories is five dimensional.Comment: 14 pages. v.2: Minor changes, some references adde

Quantum gravitational contributions to quantum electrodynamics

Quantum electrodynamics describes the interactions of electrons and photons. Electric charge (the gauge coupling constant) is energy dependent, and there is a previous claim that charge is affected by gravity (described by general relativity) with the implication that the charge is reduced at high energies. But that claim has been very controversial with the situation inconclusive. Here I report an analysis (free from earlier controversies) demonstrating that that quantum gravity corrections to quantum electrodynamics have a quadratic energy dependence that result in the reduction of the electric charge at high energies, a result known as asymptotic freedom.Comment: To be published in Nature. 19 pages LaTeX, no figure

Quantum Einstein Gravity

We give a pedagogical introduction to the basic ideas and concepts of the Asymptotic Safety program in Quantum Einstein Gravity. Using the continuum approach based upon the effective average action, we summarize the state of the art of the field with a particular focus on the evidence supporting the existence of the non-trivial renormalization group fixed point at the heart of the construction. As an application, the multifractal structure of the emerging space-times is discussed in detail. In particular, we compare the continuum prediction for their spectral dimension with Monte Carlo data from the Causal Dynamical Triangulation approach.Comment: 87 pages, 13 figures, review article prepared for the New Journal of Physics focus issue on Quantum Einstein Gravit

A prospective validation pharmacogenomic study in the adjuvant setting of colorectal cancer patients treated with the 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen

The discovery of pharmacogenomic markers in colorectal cancer (CRC) could be setting-specific. FOLFOX4 is employed in the adjuvant and metastatic setting in CRC. This prospective study is aimed to validate in the adjuvant setting the pharmacogenomic markers of toxicity reported in the metastatic setting (that is, GSTP1-rs947894, and -rs1138272; GSTM1-null genotype; AGXT-rs4426527, -rs34116584 and del-74 bp), and to discover additional markers. CRC patients (n = 144) treated with adjuvant FOLFOX4 were genotyped for 57 polymorphisms in 29 genes. Grade ≥2 neurotoxicity was associated false discovery rate-adjusted q-value <0.1) with single-nucleotide polymorphisms in ABCC1 (rs2074087: odds ratio = 0.43(0.22–0.86)), and ABCC2 (rs3740066: 2.99(1.16–7.70); rs1885301: 3.06(1.35–6.92); rs4148396: 4.69(1.60–13.74); rs717620: 14.39(1.63–127.02)). hMSH6-rs3136228 was associated with grade 3–4 neutropenia (3.23(1.38–7.57), q-value = 0.0937). XRCC3-rs1799794 was associated with grade 3–4 non-hematological toxicity (8.90(2.48–31.97), q-value = 0.0150). The markers previously identified in metastatic CRC were not validated. We have identified new markers of toxicity in genes of transport and DNA repair. If validated in other studies, they could help to identify patients at risk of toxicity

Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate

BACKGROUND: Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains. METHODOLOGY/PRINCIPAL FINDINGS: Brain homogenates from cattle with classical BSE and atypical (BASE) infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres). The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals. Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine. CONCLUSION/SIGNIFICANCE: Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products

Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson’s disease

Background: In patients with Parkinson’s disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect&nbsp;the detection of pathological α-syn. Methods: NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn. Results: In&nbsp;the first round, 72 OM samples were collected by NS, from AN (NSAN) or from MT (NSMT), and 35 resulted positive for&nbsp;α-syn&nbsp;RT-QuIC,&nbsp;including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NSAN samples and in 10/23 (44%) NSMT samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NSAN compared to NSMT. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD. Conclusion: In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as&nbsp;an ancillary procedure for PD diagnosis

Validation of Revised International Creutzfeldt-Jakob Disease Surveillance Network Diagnostic Criteria for Sporadic Creutzfeldt-Jakob Disease

IMPORTANCE: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly lethal disease. Rapid, accurate diagnosis is imperative for epidemiological surveillance and public health activities to exclude treatable differentials and facilitate supportive care. In 2017, the International CJD Surveillance Network diagnostic criteria were revised to incorporate cortical ribboning on magnetic resonance imaging and the real-time quaking-induced conversion (RT-QuIC) assay, developments that require multicenter evaluation. OBJECTIVE: To evaluate the accuracy of revised diagnostic criteria through the retrospective diagnosis of autopsy-confirmed cases (referred to as in-life diagnosis). DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study used a 3-year clinicopathological series using all cases of autopsy-confirmed sCJD and a noncase group with alternative neuropathological diagnoses from national surveillance centers in the United Kingdom, France, Germany, and Italy. Data were collected from January 2017 to December 2019 and analyzed from January 2020 to November 2021. MAIN OUTCOMES AND MEASURES: Sensitivity and specificity of revised diagnostic criteria and diagnostic investigations. Secondary analyses assessing sCJD subgroups by genotype, pathological classification, disease duration, and age. RESULTS: A total of 501 sCJD cases and 146 noncases were included. Noncase diagnoses included neurodegenerative diseases, autoimmune encephalitis, and cerebral insults such as anoxia. Participants in the sCJD cases cohort were younger (mean [SD] age, 68.8 [9.8] years vs 72.8 [10.9] years; P  .99). Among 223 cases and 52 noncases with the full panel of investigations performed, sensitivity of revised criteria (97.8%; 95% CI, 94.9%-99.3%) was increased compared with prior criteria (76.2%; 95% CI, 70.1%-81.7%; P  .99). In 455 cases and 111 noncases, cortical ribboning was 67.9% sensitive (95% CI, 63.4%-72.2%) and 86.5% specific (95% CI, 78.7%-92.2%). In 274 cases and 77 noncases, RT-QuIC was 91.6% sensitive (95% CI, 87.7%-94.6%) and 100% specific (95% CI, 96.2%-100%). Investigation sensitivity varied with genetic and pathological features, disease duration, and age. CONCLUSIONS AND RELEVANCE: This diagnostic study demonstrated significantly improved sensitivity of revised sCJD diagnostic criteria with unaltered specificity. The revision has enhanced diagnostic accuracy for clinical care and surveillance