RFPID: development and 3D-printing of a female physical phantom for whole-body counter.

Whole-body counters (WBC) are used in internal dosimetry forin vivomonitoring in radiation protection. The calibration processes of a WBC set-up include the measurement of a physical phantom filled with a certificate radioactive source that usually is referred to a standard set of individuals determined by the International Commission on Radiological Protection (ICRP). The aim of this study was to develop an anthropomorphic and anthropometric female physical phantom for the calibration of the WBC systems. The reference female computational phantom of the ICRP, now called RFPID (Reference Female Phantom for Internal Dosimetry) was printed using PLA filament and with an empty interior. The goal is to use the RFPID to reduce the uncertainties associated within vivomonitoring system. The images which generated the phantom were manipulated using ImageJ®, Amide®, GIMP®and the 3D Slicer®software. RFPID was split into several parts and printed using a 3D printer in order to print the whole-body phantom. The newly printed physical phantom RFPID was successfully fabricated, and it is suitable to mimic human tissue, anatomically similar to a human body i.e., size, shape, material composition, and density.

Unsupervised clustering to differentiate rheumatoid arthritis patients based on proteomic signatures.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have different presentations and prognoses. Cluster analysis based on proteomic signatures creates independent phenogroups of patients with different pathophysiological backgrounds. We aimed to identify distinct pathophysiological clusters of RA patients based on circulating proteomic biomarkers. METHOD: This was a cohort study including 399 RA patients. Clustering was performed on 94 circulating proteins (92 CVDII Olink®, high-sensitivity troponin T, and C-reactive protein). Unsupervised clustering was performed using a partitioning cluster algorithm. RESULTS: The clustering algorithm identified two distinct clusters: cluster 1 (n = 223) and cluster 2 (n = 176). Compared with cluster 1, cluster 2 included older patients with a higher burden of comorbidities (cardiovascular and RA related), more erosive and longer RA duration, more dyspnoea and fatigue, walking a shorter distance in the Six-Minute Walk Test, with more severe diastolic dysfunction, and a 4.5-fold higher risk of death or hospitalization for cardiovascular reasons. Tumour necrosis factor (TNF) receptor superfamily-related pathways were mainly responsible for the model's discriminative ability. CONCLUSION: Using unsupervised cluster analysis based on proteomic phenotypes, we identified two clusters of RA patients with distinct biomarkers profiles, clinical characteristics, and different outcomes that could reflect different pathophysiological backgrounds. TNF receptor superfamily-related proteins may be used to distinguish subgroups.

How has the sustainability of countries changed after COVID-19? Evidence from the pandemics' first year.

The Covid-19 crisis has caused several social-related issues; the sanitary is, perhaps, the most significant one. Lockdowns and vaccination were implemented to fight the Covid-19 virus. From a sustainability perspective, Covid-19 has been considered a meaningful crisis driver that has affected nations' economies and social and natural capitals. The literature presents clues that effects appear to be different among countries. Recognizing its importance as public policies for sustainability, this study aims to assess how the sustainability of countries has changed after Covid-19, focusing on countries' economic power that reflects their capacity to face the crisis. A sample of 89 countries is considered, and 2019-2020 are set as base years for data gathering, which covers the first year of the Covid-19 crisis. Sustainability is conceptually supported and represented by a 3-D cube. The natural environment is expressed by the ecological footprint (EF) method, the economic capital by the gross domestic product (GDP), and the social capital by the happiness index. Results show that sustainability of economies was negatively affected after first year of Covid-19 crisis, but in different magnitudes, according to nations' economic power. While the sustainability of the wealthiest economies was slightly changed during 2019-2020 but maintained within the named 'useful-order' world (environmentally unsustainable, productive, and happy), the poorest economies pushed about 169 million people into the worst performance, reaching the 'ineffective' world (environmentally unsustainable, unproductive, and unhappy). Numbers highlight the inequalities of sustainability performance among countries, according to their capacity to face the Covid-19 crisis. The shield of the richest evaluated countries comprising 5 % of the world population is more powerful than the shield of the poorest evaluated countries carrying 67 % of the world population. Results claims for efforts to make different policies and provide economic support differently for countries, since although we are all under the same storm, but in different boats.

Immunohistochemical analysis of BRCA1 and acetyl-histone H3 in squamous cell carcinoma of the mobile tongue.

OBJECTIVE: The objective of this study was to evaluate the immunoexpression profiles of breast cancer 1 (BRCA1) and acetyl-histone H3 (AcH3) in squamous cell carcinoma of the mobile tongue (SCC-MT) and their correlation with epidemiologic data and the histopathological grade of tumors. STUDY DESIGN: Incisional biopsies of 43 SCC-MT were submitted to immunohistochemistry for AcH3 and BRCA1. Samples were microscopically graded as well differentiated (n = 21) or poorly differentiated (n = 22). Both groups were submitted to statistical analysis (P < .05) regarding the percentage of positive cells. RESULTS: Thirty-nine cases were positive for AcH3 (91%), but no difference was observed for the histologic grading (P = .27). Positivity for BRCA1 was observed in all samples regardless of their cellular locations. Most cases in the poorly differentiated group presented with less than 10% nuclear staining (P < .01) and a predominance of cytoplasmic staining (P = .034). The well-differentiated group showed nuclear staining in most of the cases, with more than 50% of cells staining positive (P < .01). CONCLUSION: AcH3 and BRCA1 were expressed in all samples. There was a significant decrease in cytoplasmic BRCA1 expression in the poorly differentiated group, suggesting BRCA1 as a possible prognostic marker for SCC-MT.

Degradation of estriol (E3) and transformation pathways after applying photochemical removal processes in natural surface water.

Steroidal hormones such as estriol (E3), are resistant to biodegradation; hence their removal by conventional treatment systems (aerobic and anaerobic) facilities is limited. These substances are detected in surface water, and present risks to the aquatic ecosystem and humans via potential biological activity. Photochemical treatments can be used to remove E3; however, just a few studies have analyzed the kinetics, intermediates, and E3 degradation pathways in natural surface water. In this study, the behavior of E3 under ultraviolet irradiation associated with H2O2, O3 or TiO2 was investigated to determine the degradation potential and the transformation pathways in reactions performed with a natural surface water sample. E3 degradation kinetics (200 ppb) fitted well to the pseudo-first-order kinetics model, with kinetic constant k in the following order: kUV/O3 > kUV/TiO2 > kUV/H2O2 > kUV. The mechanism of degradation using different advanced oxidative processes seemed to be similar and 12 transformation byproducts were identified, with 11 of them being reported here for the first time. The byproducts could be formed by the opening of the aromatic ring and addition of a hydroxyl radical. A possible route of E3 degradation was proposed based on the byproducts identified, and some of the byproducts presented chronic toxicity to aquatic organisms, demonstrating the risks of exposure.

Hyperbaric oxygen therapy: a key rolein the treatment of cerebral gas embolism

Stroke is an important cause of morbidity and mortality. The etiolo-gies are varied. Gas embolism is a known complication of invasive procedures, which may complicate with cerebral embolization and ischemia. Benefits of hyperbaric oxygen therapy are recognized in cerebral gas embolism when started in the first hours after the event, which are fundamental for the vital prognosis

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Anosmia in COVID-19 Associated with Injury to the Olfactory Bulbs Evident on MRI.

Patients with coronavirus disease 2019 (COVID-19) may have symptoms of anosmia or partial loss of the sense of smell, often accompanied by changes in taste. We report 5 cases (3 with anosmia) of adult patients with COVID-19 in whom injury to the olfactory bulbs was interpreted as microbleeding or abnormal enhancement on MR imaging. The patients had persistent headache (n = 4) or motor deficits (n = 1). This olfactory bulb injury may be the mechanism by which the Severe Acute Respiratory Syndrome coronavirus 2 causes olfactory dysfunction.

Assessing cadmium-based quantum dots effect on the gonads of the marine mussel Mytilus galloprovincialis.

This study assesses the sex-specific effects induced by CdTe QDs, on the marine mussel Mytilus galloprovincialis in comparison to its dissolved counterpart. A 14 days exposure to CdTe QDs and dissolved Cd was conducted (10 µg Cd L-1), analysing Cd accumulation, oxidative stress, biotransformation, metallothionein and oxidative damage in the gonads. Both Cd forms caused significant antioxidant alterations, whereby QDs were more pro-oxidant, leading to oxidative damage, being females more affected. Overall, biochemical impairments on gonads of M. galloprovincialis demonstrate that the reproductive toxicity induced by CdTe QDs in mussels are sex-dependent and mediated by oxidative stress and lipid peroxidation. It is crucial to acknowledge how gametes are affected by metal-based nanoparticles, such as Cd-based QDs. As well as understanding the potential changes they may undergo at the cellular level during gametogenesis, embryogenesis and larval development potentially leading to serious impacts on population sustainability and ecosystem health.

Chemiluminescent ELISA with multi-epitope proteins to improve the diagnosis of canine visceral leishmaniasis.

Diagnosing canine visceral leishmaniasis (CVL) is difficult because clinical signs of the disease are non-specific and a many infected animals in endemic areas, as in Brazil, are asymptomatic. Serological tests are the most common diagnostic methods employed, but most have limitations. For this reason, the implementation of a rapid, sensitive, and specific diagnostic test for CVL has become increasingly important. In this study, we adapted a chemiluminescent enzyme-linked immunosorbent assay (CL ELISA), using two multi-epitope recombinant proteins (PQ10 and PQ20) and a crude Leishmania antigen produced using promastigotes of L. infantum, as antigens to detect CVL infection in animals from Belo Horizonte. To investigate cross-reactions, samples from dogs with other infections (babesiosis, ehrlichiosis and Trypanosoma cruzi) were tested. Assay performance validations were conducted to analyse parameters such as variability, reproducibility, and stability. CL ELISA sensitivity/specificity with PQ10 antigen was 93.1%/80.0%; with the PQ20 protein 93.1%/96.6%; and with the crude antigen 75%/73.3%. Inter-assay variability and inter-operator coefficient of variation were <7% and <15%, with PQ10 and PQ20, respectively. The accuracy of the CL ELISA was classified as excellent for PQ10 (AUC = 0.95) and PQ20 (AUC = 0.98) and moderate for the crude antigen (AUC = 0.77). The kappa score for qualitative agreement between two plate lots was excellent for PQ10 (0.89) and good for PQ20 (0.65). PQ20 remained more stable than PQ10. The CL ELISA with recombinant proteins is a promising tool to diagnose CVL.

Are shallow-water shrimps proxies for hydrothermal-vent shrimps to assess the impact of deep-sea mining?

Polymetallic seafloor massive sulphide deposits are potential targets for deep-sea mining, but high concentrations of metals (including copper - Cu) may be released during exploitation activities, potentially inducing harmful impact. To determine whether shallow-water shrimp are suitable ecotoxicological proxies for deep-sea hydrothermal vent shrimp the effects of waterborne Cu exposure (3 and 10 days at 0.4 and 4 µM concentrations) in Palaemon elegans, Palaemon serratus, and Palaemon varians were compared with Mirocaris fortunata. Accumulation of Cu and a set of biomarkers were analysed. Results show different responses among congeneric species indicating that it is not appropriate to use shallow-water shrimps as ecotoxicological proxies for deep-water shrimps. During the evolutionary history of these species they were likely subject to different chemical environments which may have induced different molecular/biochemical adaptations/tolerances. Results highlight the importance of analysing effects of deep-sea mining in situ and in local species to adequately assess ecotoxicological effects under natural environmental conditions.

Impacts of in vivo and in vitro exposures to tamoxifen: Comparative effects on human cells and marine organisms.

Tamoxifen (TAM) is a first generation-SERM administered for hormone receptor-positive (HER+) breast cancer in both pre- and post-menopausal patients and may undergo metabolic activation in organisms that share similar receptors and thus face comparable mechanisms of response. The present study aimed to assess whether environmental trace concentrations of TAM are bioavailable to the filter feeder M. galloprovincialis (100 ng L-1) and to the deposit feeder N. diversicolor (0.5, 10, 25 and 100 ng L-1) after 14 days of exposure. Behavioural impairment (burrowing kinetic), neurotoxicity (AChE activity), endocrine disruption by alkali-labile phosphate (ALP) content, oxidative stress (SOD, CAT, GPXs activities), biotransformation (GST activity), oxidative damage (LPO) and genotoxicity (DNA damage) were assessed. Moreover, this study also pertained to compare TAM cytotoxicity effects to mussels and targeted human (i.e. immortalized retinal pigment epithelium - RPE; and human transformed endothelial cells - HeLa) cell lines, in a range of concentrations from 0.5 ng L-1 to 50 µg L-1. In polychaetes N. diversicolor, TAM exerted remarkable oxidative stress and damage at the lowest concentration (0.5 ng L-1), whereas significant genotoxicity was reported at the highest exposure level (100 ng L-1). In mussels M. galloprovincialis, 100 ng L-1 TAM caused endocrine disruption in males, neurotoxicity, and an induction in GST activity and LPO byproducts in gills, corroborating in genotoxicity over the exposure days. Although cytotoxicity assays conducted with mussel haemocytes following in vivo exposure was not effective, in vitro exposure showed to be a feasible alternative, with comparable sensitivity to human cell line (HeLa).

Mast cells and immunoexpression of FGF-1 and Ki-67 in rat subcutaneous tissue following the implantation of Biodentine and MTA Angelus.

AIM: To compare the formation of fibrous capsules around Biodentine and MTA Angelus implants as well as the participation of fibroblast growth factor-1 (FGF-1) and mast cells in the tissue response to these endodontic materials. METHODOLOGY: Sixty polyethylene tubes filled with Biodentine or MTA, and empty tubes (control group) were implanted into the dorsal subcutaneous tissues of male rats. After 7, 15, 30 and 60 days, the specimens were embedded in paraffin and the number of fibroblasts and mast cells was quantified in the sections stained with Masson's trichrome or Alcian Blue, respectively. FGF-1 and Ki-67 were detected by immunohistochemistry, and the number of immunolabelled cells was computed. The collagen content was estimated in the picrosirius red-stained sections. The data were subjected to two-way ANOVA followed by Tukey's test (P ≤ 0.05). RESULTS: The capsules were associated with a significant increase (P < 0.0001) in the number of fibroblasts and mast cells, and in the collagen content over time. A significant decrease (P < 0.0001) in the immunoexpression of FGF-1 and Ki-67 was observed in all groups from the 7th-60th day. At 60 days, the number of fibroblasts (P = 0.0226) and the collagen content (P < 0.0001) were significantly greater in MTA than Biodentine specimens, while the greatest number of mast cells and FGF-1-immunolabelled cells was observed in Biodentine specimens (P < 0.0001). A significant difference in Ki-67 immunoexpression was not detected between specimens of Biodentine and MTA. CONCLUSIONS: The collagen-rich capsule formed slowly around Biodentine in comparison with MTA. FGF-1 and mast cells participated in capsule remodelling, stimulating fibroblast proliferation and subsequent collagen production, in response to subcutaneous implants.

Environmental relevant levels of the cytotoxic drug cyclophosphamide produce harmful effects in the polychaete Nereis diversicolor.

Cytotoxic drugs applied in chemotherapy enter the aquatic environment after patient's metabolism and excretion, in both main compounds and their respective metabolites. The increased consumption and discharge of these drugs raise concern on the genotoxic burden to non-target aquatic species, due to their unselective action on DNA. Settlement and adsorption of cytotoxic drugs to aquatic sediments pose risks to benthic species through chronic exposure. The aim of the present study was to assess the effects induced by the anticancer drug cyclophosphamide (CP) on the polychaete Nereis diversicolor, after 14 days of exposure to environmental relevant concentrations (10, 100, 500 and 1000 ng L-1). Burrowing impairment, neurotoxicity (Acetylcholinesterase - AChE activity), oxidative stress (superoxide dismutase - SOD; catalase - CAT; glutathione peroxidases - GPXs activities), biotransformation (glutathione-S-transferases - GST), oxidative damage (lipid peroxidation - LPO) and genotoxicity (DNA damage) were assessed. Burrowing impairments were higher at the lowest CP concentrations tested. The higher CP levels tested (500 and 1000 ng L-1) induced a significant inhibition on the enzymatic antioxidant system (SOD, GPx) and on GST activity. DNA damage was also significant at these concentrations as an outcome of CP metabolism, and high levels of oxidative damage occurred. The results showed that the prodrug CP was metabolically activated in the benthic biological model N. diversicolor. In addition to the potential cytotoxic impact likely to be caused in aquatic species with similar metabolism, N. diversicolor proved to be reliable and vulnerable to the cytotoxic mode of action of CP, even at the lower doses.

Chlorinated metronidazole as a promising alternative for treating trichomoniasis.

Trichomoniasis is the most common non-viral, sexually transmitted infection affecting humans worldwide. The main treatment for trichomoniasis is metronidazole (MTZ). However, adverse effects and reports of resistance have stimulated the development of therapeutic alternatives. The ease of manipulation of the side chains of MTZ coupled with its safety makes this molecule attractive for the development of new drugs. In this context, we evaluated the activity of the chlorinated MTZ derivative, MTZ-Cl, on sensitive and resistant strains of Trichomonas vaginalis. MTZ-Cl presented a remarkable activity against both sensitive and resistant strains. In vitro and in vivo toxicity assays indicated that the new molecule is safe for future clinical trials. Furthermore, we noticed different rates of free radical production between the sensitive and resistant strains. MTZ-Cl induced a higher release of nitric oxide (NO, ~ 9000 a.u.) by both sensitive and resistant strains. However, the sensitive strain produced a greater amount of H2O2 (~ 1,800,000 a.u.) and superoxide radicals (~ 350,000 a.u.) in the presence of MTZ. In the resistant strain, production of these radicals was more prominent when MTZ-Cl was used. Collectively, these results suggest that NO is an important molecule in the trichomonacidal activity against resistant and sensitive strains, suggesting an alternative pathway for MTZ-Cl activation. We highlight the high trichomonacidal potential of MTZ-Cl, improving the effectiveness of treatment and reducing side effects. In addition, MTZ-Cl is derived from a well-established drug on the world market that presents low toxicity to human cells, suggesting its safety to proceed with future clinical trials.

Grazing intensity affects the environmental impact of dairy systems.

Dairy products are major components of the human diet but are also important contributors to global environmental impacts. This study evaluated greenhouse gas (GHG) emissions, net energy intensity (NEI), and land use of confined dairy systems with increasing levels of pasture in the diet. A Wisconsin farm was modeled to represent practices adopted by dairy operations in a humid continental climate typical in the Great Lakes region and other climates that have large differences in seasonal temperatures. Five grazing scenarios (all of which contained some portion of confinement) were modeled based on different concentrations of dry matter intake from pasture and feed supplementation from corn grain, corn silage, and soybean meal. Scenarios that incorporate grazing consisted of 5 mo of pasture feeding from May to September and 7 mo of confined feeding from October to April. Environmental impacts were compared within the 5 scenarios that incorporate grazing and across 2 entirely confined scenarios with and without on-farm electricity production through anaerobic digestion (AD). To conduct a fair comparison, all scenarios were evaluated based on the same total amount of milk produced per day where resource inputs were adjusted according to the characteristics of each scenario. A cradle-to-farm gate life cycle assessment evaluated the environmental burdens that were partitioned by allocation between milk and meat and by system expansion when biogas-based electricity was produced. Overall, results for all scenarios were comparable. Enteric methane was the greatest contributor to GHG emissions, and the production of crops was the most energy-intense process. For the confined scenario without AD, GHG emissions were 0.87 kg of CO2 equivalents, NEI was 1.59 MJ, and land use was 1.59 m2/kg of fat- and protein-corrected milk (FPCM). Anaerobic digestion significantly reduced emissions to 0.28 kg of CO2 equivalents/kg of FPCM and reduced NEI to -1.26 MJ/kg of FPCM, indicating a net energy producing system and highlighting the potential of AD to improve the sustainability of confined systems. For scenarios that combined confinement and grazing, GHG emissions ranged from 0.84 to 0.92 kg of CO2 equivalents, NEI ranged from 1.42 to 1.59 MJ, and land use ranged from 1.19 to 1.26 m2/kg of FPCM. All environmental impacts were minimized in scenarios that supplemented enough feed to increase milk yield but maintained dry matter intake from pasture at a level high enough to reduce material and energy use.

Zirconium oxide and niobium oxide used as radiopacifiers in a calcium silicate-based material stimulate fibroblast proliferation and collagen formation.

AIM: To evaluate the influence of the addition of microparticulate (micro) and nanoparticulate (nano) zirconium oxide (ZrO2 ) and niobium pentoxide (Nb2 O5 ) to a calcium silicate-based cement (CS) on the subcutaneous healing process in rats compared with MTA Angelus™. METHODOLOGY: In each rat, two polyethylene tubes filled with the following materials: (i) MTA; (ii) CS + ZrO2 micro; (iii) CS + ZrO2 nano; (iv) CS + Nb2 O5 micro or (v) CS + Nb2 O5 nano were implanted subcutaneously; empty polyethylene tubes were used in the Control group. After 7, 15, 30 and 60 days, the specimens (n = 5 per group in each period) were fixed and embedded in paraffin. Masson's trichrome sections were used to obtain the volume density of the inflammatory cells (VvIC) and fibroblasts (VvFb). The sections were also stained with Picrosirius-red to calculate the birefringent collagen content. Fibroblast growth factor-1 (FGF-1) was detected by immunohistochemistry, and the number of immunolabelled cells was obtained. The data were subjected to two-way anova followed by Tukey's test (P ≤ 0.05). RESULTS: At all periods, the VvIC was significantly lower (P < 0.001) in all the CS and Control groups than in the MTA group. At all periods, the VvFb was reduced significantly (P = 0.023) in the MTA group in comparison with the other groups. In addition, the number of immunolabelled cells in the capsules of the CS groups was significantly higher (P < 0.001) than in the MTA group at all time-points. CONCLUSIONS: The experimental materials (CS + ZrO2 and CS + Nb2 O5 ) induced fibroblast proliferation and accelerated the regression of the inflammatory reaction. However, the addition of nanoparticulate radiopacifiers did not improve the biological properties of a calcium silicate-based cement when compared to microparticulate agents.

Ecotoxicological assessment of the anticancer drug cisplatin in the polychaete Nereis diversicolor.

Anticancer drugs are designed to inhibit tumor cell proliferation by interacting with DNA and altering cellular growth factors. When released into the waterbodies of municipal and hospital effluents these pharmaceutical compounds may pose a risk to non-target aquatic organisms, due to their mode of action (cytotoxic, genotoxic, mutagenic and teratogenic). The present study aimed to assess the ecotoxicological potential of the alkylating agent cisplatin (CisPt) to the polychaete Nereis diversicolor, at a range of relevant environmental concentrations (i.e. 0.1, 10 and 100ngPtL-1). Behavioural impairment (burrowing kinetic impairment), ion pump effects (SR Ca2+-ATPase), neurotoxicity (AChE activity), oxidative stress (SOD, CAT and GPXs activities), metal exposure (metallothionein-like proteins - MTLP), biotransformation (GST), oxidative damage (LPO) and genotoxicity (DNA damage), were selected as endpoints to evaluate the sublethal responses of the ragworms after 14-days of exposure in a water-sediment system. Significant burrowing impairment occurred in worms exposed to the highest CisPt concentration (100ngPtL-1) along with neurotoxic effects. The activity of antioxidant enzymes (SOD, CAT) and second phase biotransformation enzyme (GST) was inhibited but such effects were compensated by MTLP induction. Furthermore, LPO levels also increased. Results showed that the mode of action of cisplatin may pose a risk to this aquatic species even at the range of ngL-1.

Solvent effects on the absorption spectrum and first hyperpolarizability of keto-enol tautomeric forms of anil derivatives: A Monte Carlo/quantum mechanics study.

Theoretical results for the absorption spectrum and electric properties of the enol and keto tautomeric forms of anil derivatives in the gas-phase and in solution are presented. The electronic properties in chloroform, acetonitrile, methanol, and water were determined by carrying out sequential Monte Carlo simulations and quantum mechanics calculations based on the time dependent density functional theory and on the second-order Møller-Plesset perturbation theory method. The results illustrate the role played by electrostatic interactions in the electronic properties of anil derivatives in a liquid environment. There is a significant increase of the dipole moment in solution (20%-100%) relative to the gas-phase value. Solvent effects are mild for the absorption spectrum and linear polarizability but they can be particularly important for first hyperpolarizability. A large first hyperpolarizability contrast between the enol and keto forms is observed when absorption spectra present intense lowest-energy absorption bands. Dynamic results for the first hyperpolarizability are in qualitative agreement with the available experimental results.