As one of the most successful invasive land snail species, Achatina (Lissachatina) fulica Bowdich, 1822 has achieved wide global distribution, particularly in (sub)tropical regions, with further ...dispersal likely due to climate change. This species of giant African snails (up to 17 cm shell length) is a pest that has extensive negative impact on agriculture and can serve as vector for several parasites, including Angiostrongylus cantonensis, a nematode parasite that causes (human) eosinophilic meningitis, an emergent disease. Investigation showed that A. cantonensis infection negatively impacts the metabolism of A. fulica by depleting polysaccharide stores of the intermediate host, compromising the energy balance of the snail. A review of the literature indicates that A. fulica possesses potent innate type immune defenses to counter infection, including phagocytic hemocytes capable of deploying reactive oxygen species and lectins for non-self recognition, a serine protease-dependent coagulation response (not observed in other taxa of gastropods), as well as antimicrobial proteins including achacin, an antimicrobial protein. A recent chromosome level genome assembly will facilitate progressively detailed characterization of these immune features of A. fulica. We strongly encourage further immunological studies of A. fulica, ranging from organismal level to molecular biology to gain better understanding of the A. fulica internal defense response to nematode pathogens like A. cantonensis and the contribution of immune function to the invasiveness of (snail) species. Characterization of immunity of A. fulica, representing the understudied Stylommatophora (panpulmonate landsnails) will also broaden the comparative immunology of Gastropoda.
•The giant African snail Achatina fulica, the most widely distributed invasive pest land snail, will likely disperse further with climate change.•Achatina fulica is intermediate host for the nematode Angiostrongylus cantonensis that causes eosinophilic meningitis.•Study of metabolic and immunological aspects of this parasite host provide better understanding of epidemiology and inform on comparative immunology of gastropods.
In pursuit of potential agents to treat Chagas disease and leishmaniasis, we report the design, synthesis, and identification novel naphthoquinone hydrazide-based molecular hybrids. The compounds ...were subjected to in vitro trypanocide and leishmanicidal activities. N'-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)-3,5-dimethoxybenzohydrazide (13) showed the best performance against Trypanosoma cruzi (IC50 1.83 µM) and Leishmania amazonensis (IC50 9.65 µM). 4-Bromo-N'-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzohydrazide (16) exhibited leishmanicidal activity (IC50 12.16 µM). Regarding trypanocide activity, compound 13 was low cytotoxic to LLC-MK2 cells (SI = 95.28). Furthermore, through molecular modeling studies, the cysteine proteases cruzain, rhodesain and CPB2.8 were identified as the potential biological targets.
Microfluidics and 3D printing will allow a faster research and development in pharmaceutical and medical areas, supporting new solutions for active pharmaceutical production and clinical tests ...without the necessity of in vivo animal models. The present review aims to show the role of these two technologies in the resolution of current pharmaceutical issues (e.g., efficient continuous production of active pharmaceutical ingredients, high costs for medicine development and lack of preclinical systems capable to predict accurate human responses to new medicine drugs) and in the development of biomedical and tissue engineering. The present paper was divided into the following sections: microfluidics and active pharmaceutical ingredients synthesis, organs-on-a-chip and multiorgans microdevices, 3D printing/bioprinting, and hydrogels and bioinks. Finally, conclusions and future perspectives are exposed.
An open challenge on structural biomaterials is to obtain low-cost Ti-alloys with high elastic admissible strength (the ratio of yield strength to modulus). To reach this goal, we designed and ...characterized three quaternary alloys from the Ti-Nb-Fe system with additions of Zr and Sn. The samples were solution-treated and tested under two conditions: water-quenched and aged at 450 °C. Microstructures were analyzed with aid of scanning and transmission electron microscopy. Tensile tests performed at room-temperature confirmed a remarkable yield strength of 1271 MPa with an elastic modulus close to 90 GPa among aged Ti-19Nb-2.5Fe-6Sn (wt%) samples. Solution-treated Ti-19Nb-2.5Fe-10Zr samples presented a good combination of yield-strength and elastic modulus (1027 MPa and 69 GPa, respectively), displaying an elastic admissible strength close to 1.5. Although Zr and Sn are equally distributed between matrix and precipitates, the diffusion of Nb and Fe seem to be inhibited by the presence of Sn. As a result, Sn allows higher yield-strengths and more refined secondary α-phase, while Zr has a stronger effect on reducing the elastic modulus. In the end, a materials selection chart is presented to help designers to select materials for orthopedic implants considering the elastic admissible strain and cost as major guidelines.
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•Three novel Ti-Nb-Fe-Zr and Ti-Nb-Fe-Sn alloys were empirically developed for biomedical applications.•Zr and Sn additions reduce the omega-phase formation upon quenching, increasing ductility.•Ti-19Nb-2.5Fe-10Zr (wt%) water-quenched samples achieved an elastic admissible strength of 1.49.•After aging, Zr and Sn are equally distributed between the beta-matrix and alpha-precipitates.•Aged Ti-19Nb-2.5Fe-6Sn (wt%) samples presented a yield strength of 1271 MPa.
Coffee, one of the most produced and consumed beverage in the world, has a range of variability in its quality. The aim of this work was to evaluate the consumer capacity to perceive the coffee ...quality through their fragrance and to verify the influence of previous information about quality on this perception using hedonic scale and Check All That Apply (CATA) sensory tests. The sensory tests were performed in two stages, one without and the other with quality related information of Mogiana coffee samples (Rio, Hard and Soft), and a traditional coffee sample. CATA attributes frequency of occurrence shows that samples discrimination could be done with specific attributes. For Soft coffee the attributes with more occurrence were sweet, caramel, brown sugar, and smooth. The Hard coffee sample was described by the attributes peanut, buttery, and chocolate. While for Rio coffee, the descriptive attributes most often mentioned were strong and burnt. The traditional sample stood out among consumers for its characteristics of old, medicine, sour, burnt, unpleasant and spicy. Therefore, the use of coffee powder fragrance can be alternative to differentiate the quality of the product and its function can be enhanced by passing on information on quality attributes to consumers.
Breast cancer is the most common cancer in women worldwide. Most current guidelines recommend using multigene profiling assays to aid the decision on the addition of chemotherapy to adjuvant hormone ...therapy for women who present with early‐stage, hormone receptor‐positive, HER2‐negative disease. One of these assays is the Oncotype DX, which predicts the disease recurrence risk and adjuvant chemotherapy benefits. Given its high cost, there is an economic incentive to evaluate its surrogates, such as the Magee equations. We assessed health system costs associated with the use of the Magee scores. A probabilistic decision tree was used to calculate the difference in mean health system costs based on data obtained from a randomized trial and the published literature. Costs were calculated from a perspective of Canada's publicly funded health care system. A series of sensitivity analysis was conducted to assess the robustness of the study findings. The Magee equations were associated with a total cost savings of C$100 per patient (95% CI, −C$3068 to C$5022) compared with standard of care. The difference in costs was highly sensitive to the extent that the Magee scores could reduce the frequency of adjuvant chemotherapy and Oncotype DX requests.
A better knowledge of the differences existing between individuals who maintain cognition up to 100 years of age or more and those of the same age who present dementia syndrome may be of help in ...understanding the dementia of the very elderly people. The aim of this study was to assess cardiovascular risk factors and inflammatory markers among centenarians with and without dementia. A population-based cross-sectional study was conducted on centenarians residing in a middle-size city. Volunteers were evaluated by comprehensive geriatric assessment at home. General laboratory examinations were performed and cardiovascular risk and inflammatory activity markers were determined. Mean subject age was 101 ± 2 years, and 82 % were women. Assessment of dementia syndrome revealed that 36.4 % of the centenarians had preserved cognition. Centenarians with dementia had lower schooling (
p
< 0.01), lower body mass index (
p
= 0.02) and higher homocysteine levels (
p
< 0.01) and tended to have a lower systolic blood pressure (
p
= 0.05). Regarding the markers of inflammatory activity, demented subjects had high levels of interleukin-6 (
p
< 0.01), high-sensitivity C-reactive protein (
p
= 0.02), and erythrocyte sedimentation rate (
p
= 0.01) and lower albumin levels (
p
= 0.02) compared to centenarians without dementia. Concluding, centenarians with preserved cognition had better nutritional status, lower homocysteinemia, tendency to higher blood pressure and lower inflammatory activity compared to demented subjects.
Sympatric snail populations have been kept in the laboratory since the isolation of the parasite from the field. To evaluate the influence of the intermediate host in the infectivity of
, this ...allopatric strain was compared to two sympatric strains, from different geographical origins, and with different time of maintenance in the laboratory. Snail-trematode compatibility was accessed for a total of nine possible combinations (three snail populations, three schistosome strains), using different charges of parasite: 1, 5, 10, and 15 miracidia/snail. Each
strain was characterized according to its infectivity phenotype that reflects the efficiency of their infection mechanism and all
populations were characterized according to its (in)compatible phenotype that reflects the level of (un)susceptibility they display. For all host-parasite combinations tested the dose-response relation indicated a trend for an increase in the infectivity of
when higher miracidial doses were used. SmRES-2 presented the highest overall infectivity rate, especially in the SmRES-2/BgRES interaction with 15 miracidia/snail. However, SmRES was more infective to BgBAR than SmRES-2, indicating that SmRES strain was more infective at the first contact with this new host than after 2 years of interaction (SmRES-2). BgBAR presented the highest susceptibility to infection. SmRES and SmRES-2 are the same parasite strains. It seems that during these 2 years of interaction, BgBAR acted like a filter and shifted the compatibility polymorphism of the strain SmRES. SmRES-2 became more infective to BgRES (sympatric) than to BgBAR (allopatric), and conversely, SmRES was more infective to BgBAR (allopatric) than to BgRES (sympatric). This interplay suggests that epigenetic mechanisms are prompting these changes. This study concerns with infection of
snails from different Brazilian localities with
in allopatric and sympatric associations that will partially help in understanding the natural epidemiology of schistosomiasis within natural snail populations in watercourses. This work demonstrates that there is a shift on the compatibility polymorphism profile resulting from sympatric and allopatric interactions of
and
that constantly change during the time of interaction.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory disease without consistently effective treatment. Among the many mediators implicated in cystitis, the overproduction of ...reactive oxygen species (ROS) seems to play a key role, although the main source of ROS remains unclear. This study aimed to investigate the contribution of NADPH oxidase (NOX) isoforms in ROS generation and the voiding dysfunction of cyclophosphamide (CYP, 300 mg/Kg, ip, 24 h)-induced cystitis in adult female mice, a well-recognized animal model to study IC/BPS, by using GKT137831 (5 mg/Kg, ip, three times in a 24 h period) or GSK2795039 (5 mg/Kg, ip, three times in a 24 h period) to inhibit NOX1/4 or NOX2, respectively. Our results showed that treatment with GSK2795039 improved the dysfunctional voiding behavior induced by CYP, reduced bladder edema and inflammation, and preserved the urothelial barrier integrity and tight junction occludin expression, besides inhibiting the characteristic vesical pain and bladder superoxide anion generation. In contrast, the NOX1/4 inhibitor GKT137831 had no significant protective effects. Taken together, our in vivo and ex vivo data demonstrate that NOX2 is possibly the main source of ROS observed in cystitis-induced CYP in mice. Therefore, selective inhibition of NOX2 by GSK2795039 may be a promising target for future therapies for IC/BPS.
The blue emission of a carbamic acid oligo(2-methyl-2-oxazoline) synthesized by a cationic ring-opening polymerization in supercritical carbon dioxide under controlled conditions is reported. The ...increase of the light-emission intensity of oligo(2-oxazoline)s was achieved by carbamic acid insertion at the oligomer starting end during the polymerization. Successful labeling of gram-positive S. aureus bacterial cells with carbamic acid ammonium-quaternized oligo(2-oxazoline)s turn these materials into promising blue fluorescent markers for imaging and bioanalytical assays.
► Synthesis of carbamic acid enriched oligo(2-oxazoline)s (OOXs) in scCO2 is reported. ► Fluorescence of enriched carbamic acid OOXs is reported for the first time. ► Light-emission properties can be tuned by scCO2 synthetic route. ► Purely intrinsic blue emission of OOXs results from carbamic acid endcapping. ► Ammonium-quaternized OOXs can be used as blue markers for S. aureus cells.
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