Antimicrobial and antibiofilm activities of Inga cylindrica trypsin inhibitor.

Inga cylindrica, a tropical fruit tree of the Fabaceae family (subfamily Mimosoideae), is native to South America. The seeds from this family are an essential source of trypsin inhibitors, which display promising bioactivity for increasing host defense against pathogens. The aim of the present study was to characterize the antimicrobial and antibiofilm activities of the trypsin inhibitor extracted from I. cylindrica seeds, ICTI. ICTI demonstrated antifungal activity with a minimum inhibitory concentration (MIC) of 32.11 µmol.L-1, and a minimum fungicidal concentration (MFC) of 32.1 µmol.L-1, against Cryptococcus gattii, Candida albicans, Candida glabrata and Candida guilliermondii. Combining ICTI with Amphotericin B had a significant synergistic effect, reducing the concentration of the antibiotic by 75% for C. albicans and 94% for C. gatti. The significant increase (16 x) in activity observed with ergosterol (1.01 mol.L-1) for C. albicans and C. gatti, and the lack of activity against bacterial strains, suggests that ICTI interferes with the integrity of the fungal cell membrane. Treatment with ICTI at 10 x MIC resulted in a 51% reduction in biofilm formation and a 56% decrease in mature biofilm colonies for C. albicans. Finally, ICTI displayed no toxicity in the in vivo Galleria mellonella model. Given its antifungal and antibiofilm properties, ICTI could be a promising candidate for the development of new antimicrobial drug prototypes.

Guarana (Paullinia cupana) as a potential tool for mesenchymal stromal cells priming in regenerative medicine.

Mesenchymal stromal cells (MSCs) have therapeutic potential due to their abilities of differentiation, immunomodulation, and migration to injured tissues, potentiating such effects when cells are activated. Guarana (Paullinia cupana) is a tropical plant species found in South America that is known for its antioxidant, stimulant, and cicatricial effects. The guarana extract is composed of many substances and caffeine is the main component. The objective was to evaluate the effects of guarana and caffeine on MSCs. After the initial characterization, MSCs were treated with Paullinia cupana (10, 100, and 1000 µg/mL) or caffeine (0.4, 4, and 40 µg/mL) for 24 h. MSCs treatment with 1000 µg/mL guarana increased cell polarity, viability, cell migration to chemoattractant, antioxidant potential, and liberation of extracellular vesicles (EVs), while it reduced the levels of autophagy. MSCs treated with 100 and 1000 µg/mL guarana or 40 µg/mL caffeine showed a decrease of cell proliferation. No treatment affected the cellular area and cell cycle of MSCs. The study shows in vitro evidence that guarana could be a promising alternative for activating MSCs to promote better cellular products for future clinical therapies.

Ontogenetic and sexual differences in the venom of Bothrops moojeni: insights from a litter and its mother.

Variability in snake venom composition is well-documented and crucial for understanding snake ecology and predicting snakebites. In this study, we characterize the venom composition and biological activities of newborn female and male Bothrops moojeni and their mother. Our results reveal significant differences between the venom of newborn females and males, demonstrating a broad and diverse range of proteins. The venoms of newborn females showed higher serine protease effects, increased hemorrhagic activity, and greater lethality compared to the venom of newborn males. However, no differences were observed in phospholipase A2 and coagulant activity. The differences in protein composition and toxic activities between maternal and neonatal venom, as well as between the venoms of newborn females and males, contribute to understanding the diverse outcomes of snakebites. These results underscore the importance of considering sex and ontogeny in understanding venom composition in snakes.

Ternary composites of poly(vinylidene fluoride-co-hexafluoropropylene) with silver nanowires and titanium dioxide nanoparticles as separator membranes for lithium-ion batteries.

In the realm of polymer composites, there is growing interest in the use of more than one filler for achieving multifunctional properties. In this work, a composite separator membrane has been developed for lithium-ion battery application, by incorporating conductive silver nanowires (AgNWs) and titanium dioxide (TiO2) nanoparticles into a poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) polymer matrix. The composite membranes were manufactured by solvent casting and thermally induced phase separation, with total filler content varying up to 10 wt%. The ternary composites composites present improved mechanical characteristics, ionic conductivity and lithium transfer number compared to the neat polymer matrix. On the other hand, the filler type and content within the composite has little bearing on the morphology, polymer phase, or thermal stability. Once applied as a separator in lithium-ion batteries, the highest discharge capacity value was obtained for the 5 wt% AgNWs/5 wt% TiO2/PVDF-HFP membrane at different C-rates, benefiting from the synergetic effect from both fillers. This work demonstrates that higher battery performance can be achieved for next-generation lithium-ion batteries by using separator membranes based on ternary composites.

Guarana (Paullinia cupana) as a potential tool for mesenchymal stromal cells priming in regenerative medicine

Mesenchymal stromal cells (MSCs) have therapeutic potential due to their abilities of differentiation, immunomodulation, and migration to injured tissues, potentiating such effects when cells are activated. Guarana (Paullinia cupana) is a tropical plant species found in South America that is known for its antioxidant, stimulant, and cicatricial effects. The guarana extract is composed of many substances and caffeine is the main component. The objective was to evaluate the effects of guarana and caffeine on MSCs. After the initial characterization, MSCs were treated with Paullinia cupana (10, 100, and 1000 μg/mL) or caffeine (0.4, 4, and 40 μg/mL) for 24 h. MSCs treatment with 1000 μg/mL guarana increased cell polarity, viability, cell migration to chemoattractant, antioxidant potential, and liberation of extracellular vesicles (EVs), while it reduced the levels of autophagy. MSCs treated with 100 and 1000 μg/mL guarana or 40 μg/mL caffeine showed a decrease of cell proliferation. No treatment affected the cellular area and cell cycle of MSCs. The study shows in vitro evidence that guarana could be a promising alternative for activating MSCs to promote better cellular products for future clinical therapies.

Exploring the potential of Eu3+ and Mn4+ activated LaAlO3 phosphors as red and far-red emitters for horticulture lighting.

The development of efficient red and far-red emitters, for efficient plant absorption in the Photosynthetically Active Radiation (PAR) region, holds significance in contemporary plant growth control. This study focuses on the synthesis and characterization of LaAlO3 as a host material, doped with Eu3+ and Mn4+ ions, using a solid-state reaction method. The investigation encompasses the creation and analysis of both single-doped and co-doped samples, employing techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), and photoluminescence (PL) spectroscopy. XRD analysis consistently confirmed the perovskite-like structure of all samples, devoid of detectable impurities or major structural changes due to doping. SEM images revealed a uniform distribution of regularly shaped particles for the co-doped sample. The PL spectroscopy showed that the doping led to strong photoluminescence, with the co-doped sample exhibiting the intensity of each of the ions independently neither exhibiting quenching nor energy transfer mechanisms. The excitation spectrum of Eu3+ exhibited a broad charge transfer band at approximately 328 nm, coupled with characteristic f-f excitation bands. On the other hand, the Mn4+ ion's excitation spectrum featured transitions from ground state (4A2g) electrons excited to higher excited states (4T1g, 2T2g, and 4T2g) centered at 350 nm and within the region 250-550 nm. The co-doped sample was excited at a common excitation wavelength of 460 nm and underwent an in-depth examination of its photoluminescent properties, including decay curves analysis and time dependence also. The results from this study suggest that the synthesized phosphor materials exhibit substantial potential for diverse applications, including but not limited to solid-state lighting for efficient plant growth.

Extubação paliativa em uma unidade de terapia intensiva cardiológica ­ um relato de caso / Palliative extubation in a cardiac intensive care unit ­ a case report

INTRODUÇÃO: A extubação paliativa é descrita como a retirada do tubo traqueal e da ventilação mecânica, quando todas as possibilidades de desmame ventilatório falharam ou o prognóstico do paciente é desfavorável. É um procedimento que evita prolongar a vida de maneira artificial e deve ser acordado juntamente com os familiares e a equipe. OBJETIVO: Relatar um caso de extubação paliativa numa unidade de terapia intensiva cardiológica. MÉTODO: Relato de caso RESULTADOS: Paciente do sexo feminino, portadora de Miocardiopatia Dilatada deu entrada no pronto-socorro em Insuficiência Cardíaca perfil C. Após a realização das medidas farmacológicas e o uso de ventilação não invasiva, não houve resposta satisfatória, evoluindo para intubação orotraqueal. A extubação ocorreu após 6 dias, porém em 24 horas houve falha de extubação, seguida de parada cardiorrespiratória (PCR) de 15 minutos. Foram realizadas todas as medidas pós PCR e mesmo a compensação clínica, não houve resposta neurológica favorável para progredir com uma nova extubação, desse modo, a equipe definiu os Cuidados Paliativos. O filho da paciente trouxe o relato de que ela não gostaria de viver de forma artificial e mesmo estando apreensivo com a possibilidade de óbito iminente após a extubação, visto que a mãe não tinha resposta favorável, ele não gostaria que mantivéssemos as medidas invasivas. Após uma conferência familiar com consenso entre a equipe e os familiares optou-se por realizar a extubação paliativa, para tal houve a suspensão de medicamentos não essenciais e foi otimizado as medicações para prevenir o estridor laríngeo. Para a extubação, foi realizado aspiração de alívio e o teste de respiração espontânea com resposta satisfatória e após 19 dias de intubação a paciente foi extubada, o procedimento ocorreu de maneira tranquila, não houve necessidade de aspiração ou suplementação com oxigênio, a paciente permaneceu com um Glasgow 6, eupneica em ar ambiente com uma fisionomia confortável, sem sinais de desconforto respiratório ou de dor. O atendimento fisioterapêutico foi mantido visando manter o conforto, a paciente teve o acompanhamento dos familiares com visita estendida e veio a falecer após 4 dias da extubação. CONCLUSÃO: A extubação paliativa ocorreu com o suporte da equipe e dos familiares, livre de dor ou desconforto e a paciente veio a falecer 4 dias após o procedimento. Esse relato de caso reforça a importância do alinhamento de condutas, da presença da família e a possibilidade de sobrevida após uma extubação paliativa.

High levels of NRF2 sensitize temozolomide-resistant glioblastoma cells to ferroptosis via ABCC1/MRP1 upregulation.

Glioblastoma patients have a poor prognosis mainly due to temozolomide (TMZ) resistance. NRF2 is an important transcript factor involved in chemotherapy resistance due to its protective role in the transcription of genes involved in cellular detoxification and prevention of cell death processes, such as ferroptosis. However, the relation between NRF2 and iron-dependent cell death in glioma is still poorly understood. Therefore, in this study, we analyzed the role of NRF2 in ferroptosis modulation in glioblastoma cells. Two human glioblastoma cell lines (U251MG and T98G) were examined after treatment with TMZ, ferroptosis inducers (Erastin, RSL3), and ferroptosis inhibitor (Ferrostatin-1). Our results demonstrated that T98G was more resistant to chemotherapy compared to U251MG and showed elevated levels of NRF2 expression. Interestingly, T98G revealed higher sensitivity to ferroptosis, and significant GSH depletion upon system xc- blockage. NRF2 silencing in T98G cells (T98G-shNRF2) significantly reduced the viability upon TMZ treatment. On the other hand, T98G-shNRF2 was resistant to ferroptosis and reverted intracellular GSH levels, indicating that NRF2 plays a key role in ferroptosis induction through GSH modulation. Moreover, silencing of ABCC1, a well-known NRF2 target that diminishes GSH levels, has demonstrated a similar collateral sensitivity. T98G-siABCC1 cells were more sensitive to TMZ and resistant to Erastin. Furthermore, we found that NRF2 positively correlates with ABCC1 expression in tumor tissues of glioma patients, which can be associated with tumor aggressiveness, drug resistance, and poor overall survival. Altogether, our data indicate that high levels of NRF2 result in collateral sensitivity on glioblastoma via the expression of its pro-ferroptotic target ABCC1, which contributes to GSH depletion when the system xc- is blocked by Erastin. Thus, ferroptosis induction could be an important therapeutic strategy to reverse drug resistance in gliomas with high NRF2 and ABCC1 expression.

Magnesium Supplementation Is Associated with a Lower Cardio-Metabolic Risk in Patients Submitted to Bariatric Surgery.

PURPOSE: Literature has demonstrated an inverse relation between magnesium (Mg) consumption and development of type 2 diabetes mellitus (T2DM), hypertension (HT), and dyslipidemia. After bariatric surgery (BS), micronutrients deficiencies are common, it being important to ensure appropriate supplementation. There is no recommendation about Mg supplementation and to our knowledge, its effect has not been studied to date. Our aim was to evaluate the effect of Mg supplementation in cardio-metabolic risk factors on post-bariatric patients. MATERIALS AND METHODS: A retrospective observational study of patients with obesity who underwent BS was performed. Data was assessed preoperatively and yearly (4-year follow-up). RESULTS: A total of 3363 patients were included. In the first year of follow-up, 79.8% (n = 2123) of the patients were supplemented with Mg, with evidence of slightly decreased percentages in the following years. Mg deficiency (serum Mg < 1.52 mEq/L) was more common among patients who were not supplemented during each year of follow-up (p < 0.05). Among those who underwent Mg supplementation, the percentage of T2DM, HT, or low-density lipoprotein cholesterol (LDL-C) > 130 mg/dL was significantly lower. In the first year post-surgery, the supplementation group had a lower risk of T2DM (OR = 0.545, p < 0.0001), LDL-C > 130 mg/dL (OR = 0.612, p < 0.0001), and HT (OR = 0.584, p < 0.0001). The OR for having these metabolic comorbidities persisted lower during the 4 years' follow-up. Patients who had Mg deficiency had higher prevalence of T2DM and HT. CONCLUSION: Mg supplementation seems to have a protective effect on the development of T2DM, HT, and LDL-C > 130 mg/dL in post-bariatric patients.

Modeling the association between socioeconomic features and risk of flood damage: A local-scale case study in Sri Lanka.

Floods cause severe damage to people as well as to properties. The same flood can cause different levels of damage to different households, but investigations into floods tend to be conducted on regional and national scales, thereby missing these local variations. It is therefore necessary to understand individual experiences of flood damage to implement effective flood management strategies on a local scale. The main objectives of this study were to develop a model that represents the relationship between socioeconomic conditions and flood damage at a local scale, and to understand the socioeconomic factors most closely tied to flood damage. The analysis is novel in that it considers not only the impact of flood characteristics, but also the impact of social, economic, and geographic factors on flood damage. This analysis derives from a quantitative modeling approach based on community responses, with the responses obtained through questionnaire surveys that consider four consecutive floods of differing severity. Path analysis was used to develop a model to represent the relationships between these factors. A randomly selected sample of 150 data points was used for model development, and nine random samples of 150 data points were used to validate the model. Results suggest that poor households, located in vulnerable, low-lying areas near rivers, suffer the most from being exposed to frequent, severe floods. Further, the results show that the socioeconomic factors with the most significant bearing on flood damage are per capita income and geographic location of the household. The results can be represented as a cycle, showing that social, economic, geographic, and flood characteristics are interrelated in ways that influence flood damage. This empirical analysis highlights a need for local-scale flood damage assessments, as offered in this article but seldom seen in other relevant literature. Our assessment was achieved by analyzing the impact of socioeconomic and geographic conditions and considering the relationship between flood characteristics and flood damage.

White LED phototherapy as an improved treatment for neonatal jaundice.

With the aim of improving phototherapy for neonatal jaundice (hyperbilirubinemia), this study investigates the degradation of unconjugated bilirubin under irradiance by conventional light and by white, red, green, and blue LED sources in vitro. The absorption spectra of bilirubin under these different light sources are compared. The results demonstrate that white LED phototherapy promotes more efficient bilirubin degradation than conventional blue-light therapy. This study provides a basis for the design of novel phototherapy devices for the treatment of hyperbilirubinemia.

Patterned separator membranes with pillar surface microstructures for improved battery performance.

In order to improve battery performance by tuning battery separator membranes, this work reports on porous poly(vinylidene fluoride-co-trifluoroethylene) - P(VDF-TrFE)- membranes with surface pillar microstructures. Separators with tailored pillar diameter, height and bulk thickness were fabricated by template patterning and computer simulations, allowing to evaluate the effect of the pillar microstructure characteristics on battery performance. It is shown that the different pillar microstructures of the separators affect the uptake value (150-325%), ionic conductivity value (0.8-1.6 mS·cm-1) and discharge capacity of the lithium ion batteries (LIB) when compared with the separator without pillars. The experimental charge-discharge behavior demonstrates that the pillar parameters affect battery performance and the best microstructure leading to 80 mAh·g-1 at 2C. Battery performance can be thus optimized by adjusting pillar diameter, height and bulk thickness of the separators keeping its volume constant, as demonstrated also by the simulation results. The parameter with most influence in battery performance is the bulk thickness of the separator, allowing to obtain a maximum discharge capacity value of 117.8 mAh·g-1 at 90C for a thickness of 0.01 mm. Thus, this work shows that the optimization of the pillar microstructure of the separator membranes allows increasing the capacity towards a new generation of high-performance LIBs.

Enhanced ionic conductivity in poly(vinylidene fluoride) electrospun separator membranes blended with different ionic liquids for lithium ion batteries.

Electrospun poly(vinylidene fluoride) (PVDF) fiber membranes doped with different ionic liquids (ILs) and sharing the same anion were produced and their potential as separator membranes for battery applications was evaluated. Different types of ILs containing the same anion, bis(trifluoromethylsulfonyl)imide [TFSI]-, were used with IL concentrations ranging between 0 and 15 wt% The morphology, microstructure, thermal and electrical properties (ionic conductivity and electrochemical window) of the membranes were evaluated. The presence of ILs in the PVDF polymer matrix influences the fiber diameter and the content of the polar ß phase within the polymer, as well as the degree of crystallinity. The thermal stability of the membranes decreases with the incorporation of IL. Impedance spectroscopy tests show a maximum ionic conductivity of 2.8 mS.cm-1 for 15% of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Emim][TFSI]) at room temperature. The electrochemical stability of the samples ranges from 0.0 to 6.0 V. When evaluated as battery separator membranes in C-LiFePO4 half-cells, a maximum discharge capacity of 119 mAh.g-1 at C-rate was obtained for the PVDF membrane with 15% [Emim][TFSI], with a coulombic efficiency close to 100%. The results demonstrate that the produced electrospun membranes are suitable for applications as separators for lithium ion batteries (LIBs).

Negatively controlled, randomized clinical trial comparing different antimicrobial interventions for treatment of clinical mastitis caused by gram-positive pathogens.

The general objective of this study was to evaluate the effect of 3 intramammary antibiotic interventions using 2 commercially available antibiotics with narrow- or broad-spectrum activity on cure rates of clinical mastitis (CM) caused by gram-positive bacteria. We also compared the efficacy of treatment protocols, including a negative control, on outcomes at the cow and mammary quarter level. Before the onset of the study, 5,987 animals more than 12 mo old were randomly preassigned to 1 of 4 protocols in the event of gram-positive CM (except for Staphylococcus aureus and Trueperella pyogenes) during lactation: 3 infusions with 62.5 mg of amoxicillin performed 12 h apart (AMOX-L); 5 infusions once a day with 62.5 mg of amoxicillin (AMOX-EL); 5 infusions once a day with 125 mg of ceftiofur hydrochloride (CEFT-L); or negative control, no treatment performed until 5 d after diagnosis (NEG-CTR). Randomization was performed to preassign 90% of cows to one of the antibiotic protocols (30% in each group) and 10% to the negative control. A total of 696 quarter cases of CM met the inclusion criteria and were evaluated in the study. Quarter-level outcomes were assessed based on 5 milk samples collected up to 14 ± 3 d following enrollment (i.e., first day of treatment), whereas variables at the cow level [composite somatic cell count (SCC), milk production, and survival in the herd] were assessed up to 90 d after CM diagnosis. Streptococcus uberis, followed by Streptococcus dysgalactiae, were the main causes of gram-positive CM. Overall, clinical cure was higher for CEFT-L than for AMOX-EL, and no difference was observed between CEFT-L and AMOX-L. Likewise, no significant differences were detected on overall bacteriological cure, although some treatment effects were observed at the species level. Compared with antibiotic-treated groups, quarters assigned to NEG-CTR had higher counts of colony-forming units (cfu), 16S rRNA gene copy numbers, and Streptococcus relative abundance (RA) until d 5 after enrollment. Quarters treated with AMOX-L had higher cfu counts on d 5, 8, and 14 after enrollment compared with the other antibiotic protocols. In addition, the RA of Streptococcus spp. was higher on d 14 after enrollment for AMOX-treated quarters compared with the CEFT-L group. Linear score of SCC was higher for AMOX-treated cows than for CEFT-L in the first test day after CM. However, cows assigned to AMOX-L had higher milk production than those submitted to the AMOX-EL and CEFT-L protocols. In conclusion, the 2-d protocol with 3 intramammary infusions of amoxicillin (narrow-spectrum antimicrobial) had similar overall clinical and bacteriological cures as 5 administrations (once a day) with ceftiofur hydrochloride (wide spectrum). No significant difference was observed on CM recurrence and cow survival. However, quarters treated with 5-d protocols were more effective at reducing milk cfu counts than quarters in the AMOX-L protocol. In addition, lower Streptococcus spp. RA was observed in ceftiofur-treated quarters compared with the amoxicillin protocols at d 14 after CM diagnosis. Based on results of microbiome and bacterial load (quantitative PCR and cfu count) up to 5 d after CM diagnosis, antibiotic use remains an indispensable strategy for treatment of CM caused by gram-positive bacteria.

Differential responses of genes and enzymes associated with ROS protective responses in the sugarcane smut fungus.

The fungal pathogen Sporisorium scitamineum causes sugarcane smut disease. We have previously shown that resistant sugarcane plants induce ROS, coinciding with a delay in fungal colonization. Here, we investigated whether the fungus modifies the enzymatic antioxidant system in vitro and when colonizing sugarcane tissues in response to ROS. In vitro, the exposure to ROS did not affect cell integrity, and a combination of superoxide dismutases (SOD) and catalases (CAT) were active. In vitro, the fungus did not alter the expression of the transcriptional regulator Yap1 and the effector Pep1. The fungus activated distinct enzymes when colonizing plant tissues. Instead of CAT, S. scitamineum induced glutathione peroxidase (Gpx) expression only when colonizing smut-resistant plants. Yap1 had an earlier expression in both smut-susceptible and -resistant plants, with no apparent correlation with the expression of antioxidant genes sod, cat, gpx, or external redox imbalance. The expression of the effector pep1 was induced only in smut-resistant plants, potentially in response to ROS. These results collectively suggest that S. scitamineum copes with oxidative stress by inducing different mechanisms depending on the conditions (in vitro/in planta) and intensity of ROS. Moreover, the effector Pep1 is responsive to the stress imposed only by the sugarcane resistant genotype.

Pontine Myelinolysis Caused by Hypovolemic Hypernatremia.

Introduction. Central pontine myelinolysis is characterized by the occurrence of acute demyelinating lesions of cells in the pons secondary to abrupt oscillations of serum osmolarity. Its exact incidence is not well defined, but studies show a prevalence of 0.25 to 0.5% in the general population, 2.5% in the intensive care unit, and up to 10% in patients with risk factors, such as chronic liver disease and hepatic transplantation, alcoholism, malnutrition, diuretic therapy, electrolyte imbalance, hypoglycemia, and hyperglycemia. Case Report. A 70-year-old white female with extranodal diffuse large B-cell non-Hodgkin's lymphoma (extensive mass on the left anterior chest wall), stage IVA, developed pontine myelinolysis secondary to hypovolemic acute hypernatremia, which occurred due to diarrhea caused by chemotherapy (rituximab, cyclophosphamide, doxorubicin, and vincristine). Discussion. Pontine myelinolysis occurs most often due to the rapid correction of chronic hyponatremia. But here, we describe a case of the disease secondary to the occurrence of hypovolemic acute hypernatremia in a patient with a hematological malignancy under treatment, who was on chronic treatment with thiazide diuretics and who presented with other electrolyte disturbances as risk factors for the development of pontine myelinolysis.