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1.
J Hazard Mater ; 480: 135948, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39342844

RESUMO

Biofilms in drinking water (DW) systems persistently challenge traditional disinfection methods due to intricate microbial interactions, with coaggregation playing a crucial role in forming multispecies biofilms. This study examined the implications of coaggregation on tolerance towards sodium hypochlorite (NaOCl) disinfection. Dual-species biofilms were formed for seven days on polyvinyl chloride coupons, comprising a strain of the emerging pathogen Stenotrophomonas maltophilia and the coaggregating strain Delftia acidovorans 005 P. For comparison, dual-species biofilms were also formed with a non-coaggregation strain (D. acidovorans 009 P). The minimum bactericidal concentration (MBC) for each planktonic strain varied (D. acidovorans: 1 mg/L, S. maltophilia: 1.5 mg/L) below the safe DW treatment limits. However, high NaOCl doses (10 ×MBC and 100 ×MBC,) showed low efficacy against dual-species biofilms, indicating significant biofilm tolerance to disinfection. Membrane damage occurred at sub-MBC without culturability loss, underscoring biofilm resilience. The biofilm analysis revealed a complex interplay between the composition of extracellular polymeric substances and the architecture, which was influenced by the presence of the coaggregating strain. Overall, coaggregation significantly influenced biofilm formation and resilience, impacting NaOCl disinfection. These findings underscore the challenges of microbial interactions in biofilms, emphasizing the need for improved disinfection strategies to control biofilms in drinking water systems.

2.
Sci Total Environ ; 951: 175646, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39168334

RESUMO

The biofilm architecture is significantly influenced by external environmental conditions. Biofilms grown on drinking water distribution systems (DWDS) are exposed to environmental contaminants, including parabens, and disinfection strategies, such as chlorine. Although changes in biofilm density and culturability from chemical exposure are widely reported, little is known about the effects of parabens and chlorine on biofilm morphology and architecture. This is the first study evaluating architectural changes in Stenotrophomonas maltophilia colony biofilms (representatives of bacterial communities presented in DWDS) induced by the exposure to methylparaben (MP) at environmental (15 µg/L) and in-use (15 mg/L) concentrations, and chlorine at 5 mg/L, using widefield epi-fluorescence mesoscopy with Mesolens. The GFP fluorescence of colony biofilms allowed the visualization of internal structures and Nile Red fluorescence permitted the inspection of the distribution of lipids. Our data show that exposure to MP triggers physiological and morphological adaptation in mature colony biofilms by increasing the complexity of internal structures, which may confer protection to embedded cells from external chemical molecules. These architectural modifications include changes in lipid distribution as an adaptive response to MP exposure. Although chlorine exposure affected colony biofilm diameter and architecture, the colony roundness was completely affected by the simultaneous presence of MP and chlorine. This work is pioneer in using Mesolens to highlight the risks of exposure to emerging environmental contaminants (MP), by affecting the architecture of biofilms formed by drinking water (DW) bacteria, even when combined with routine disinfection strategies.


Assuntos
Biofilmes , Cloro , Parabenos , Stenotrophomonas maltophilia , Poluentes Químicos da Água , Biofilmes/efeitos dos fármacos , Parabenos/toxicidade , Stenotrophomonas maltophilia/efeitos dos fármacos , Stenotrophomonas maltophilia/fisiologia , Cloro/farmacologia , Cloro/toxicidade , Poluentes Químicos da Água/toxicidade , Desinfetantes/toxicidade , Água Potável/microbiologia
3.
Sci Total Environ ; 948: 174872, 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-39032752

RESUMO

Bacterial coaggregation is a highly specific type of cell-cell interaction, well-documented among oral bacteria, and involves specific characteristics of the cell surface of the coaggregating strains. However, the understanding of the mechanisms promoting coaggregation in aquatic systems remains limited. This gap is critical to address, given the broad implications of coaggregation for multispecies biofilm formation, water quality, the performance of engineered systems, and diverse biotechnological applications. Therefore, this study aims to comprehensively characterize the cell surface of the coaggregating strain Delftia acidovorans 005P, isolated from drinking water, alongside a non-coaggregating strain, D. acidovorans 009P. By analyzing two strains of the same species, we aim to identify the factors contributing to the coaggregation ability of strain 005P. To achieve this, we employed a combination of physicochemical characterization, Fourier-transform infrared spectroscopy (FTIR), and advancing imaging techniques [transmission electron microscopy and cryo-electron tomography (cryo-ET)]. The coaggregating strain (005P) exhibited higher surface hydrophobicity, negative surface charge, and cell surface and co-adhesion energies than the non-coaggregating strain (009P). The chemical characterization of bacterial surfaces through FTIR revealed subtle differences, particularly in spectral regions linked to carbohydrates and phosphodiesters/amide III of proteins (860-930 cm-1 and 1212-1240 cm-1, respectively). Cryo-ET highlighted significant differences in pili structures between the strains, such as variations in length, frequency, and arrangement. The pili in the 005P strain, identified as pili-like adhesins, serve as key mediators of coaggregation. By integrating physicochemical analyses and high-resolution imaging techniques, this study conclusively links the coaggregation ability of D. acidovorans 005P to its unique pili characteristics, emphasizing their crucial role in microbial coaggregation in aquatic environments.


Assuntos
Aderência Bacteriana , Biofilmes , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície
4.
Biol Methods Protoc ; 9(1): bpae035, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835855

RESUMO

The gold standard for coronavirus disease 2019 diagnostic testing relies on RNA extraction from naso/oropharyngeal swab followed by amplification through reverse transcription-polymerase chain reaction (RT-PCR) with fluorogenic probes. While the test is extremely sensitive and specific, its high cost and the potential discomfort associated with specimen collection made it suboptimal for public health screening purposes. In this study, we developed an equally reliable, but cheaper and less invasive alternative test based on a one-step RT-PCR with the DNA-intercalating dye SYBR Green, which enables the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly from saliva samples or RNA isolated from nasopharyngeal (NP) swabs. Importantly, we found that this type of testing can be fine-tuned to discriminate SARS-CoV-2 variants of concern. The saliva RT-PCR SYBR Green test was successfully used in a mass-screening initiative targeting nearly 4500 asymptomatic children under the age of 12. Testing was performed at a reasonable cost, and in some cases, the saliva test outperformed NP rapid antigen tests in identifying infected children. Whole genome sequencing revealed that the antigen testing failure could not be attributed to a specific lineage of SARS-CoV-2. Overall, this work strongly supports the view that RT-PCR saliva tests based on DNA-intercalating dyes represent a powerful strategy for community screening of SARS-CoV-2. The tests can be easily applied to other infectious agents and, therefore, constitute a powerful resource for an effective response to future pandemics.

5.
Phys Chem Chem Phys ; 26(26): 18244-18255, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38904333

RESUMO

Natural deep eutectic solvents (NADESs) comprised of osmolytes are of interest as potential biomolecular (cryo)protectants. However, the way these solvents influence the structure and dynamics of biomolecules as well as the role of water remains poorly understood. We carried out principal component analysis of various secondary structure elements of ubiquitin in water and a betaine : glycerol : water (1 : 2 : ζ; ζ = 0, 1, 2, 5, 10, 20, 45) NADES, from molecular dynamics trajectories, to gain insight into the protein dynamics as it undergoes a transition from a highly viscous anhydrous to an aqueous environment. A crossover of the protein's essential dynamics at ζ ∼ 5, induced by solvent-shell coupled fluctuations, is observed, indicating that ubiquitin might (re)fold in the NADES upon water addition at ζ > ∼5. Further, in contrast to water, the anhydrous NADES preserves ubiquitin's essential modes at high temperatures explaining the protein's seemingly enhanced thermal stability.


Assuntos
Ubiquitina , Água , Betaína/química , Glicerol/química , Simulação de Dinâmica Molecular , Análise de Componente Principal , Estrutura Secundária de Proteína , Solventes/química , Ubiquitina/química , Água/química
6.
J Hazard Mater ; 476: 134883, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38897118

RESUMO

Parabens are emerging contaminants that have been detected in drinking water. Their presence in DW distribution systems (DWDS) can alter bacterial behaviour, characteristics, and structure, which may compromise DW disinfection. This work provides insights into the impact of methylparaben (MP) on the tolerance to chlorine disinfection and antibiotics from dual-species biofilms formed by Acinetobacter calcoaceticus and Stenotrophomonas maltophilia isolated from DW and grown on high-density polyethylene (HDPE) and polypropylene (PPL). Results showed that dual-species biofilms grown on PPL were more tolerant to chlorine disinfection, expressing a decrease of over 50 % in logarithmic reduction values of culturable cells in relation to non-exposed biofilms. However, bacterial tolerance to antibiotics was not affected by MP presence. Although MP-exposed dual-species biofilms grown on HDPE and PPL were metabolically more active than non-exposed counterparts, HDPE seems to be the material with lower impact on DW risk management and disinfection, if MP is present. Overall, results suggest that MP presence in DW may compromise chlorine disinfection, and consequently affect DW quality and stability, raising potential public health issues.


Assuntos
Biofilmes , Cloro , Desinfetantes , Desinfecção , Parabenos , Biofilmes/efeitos dos fármacos , Parabenos/toxicidade , Cloro/farmacologia , Desinfecção/métodos , Desinfetantes/farmacologia , Desinfetantes/toxicidade , Acinetobacter calcoaceticus/efeitos dos fármacos , Stenotrophomonas maltophilia/efeitos dos fármacos , Polipropilenos , Polietileno , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Purificação da Água/métodos , Poluentes Químicos da Água/toxicidade
7.
Cureus ; 16(4): e58033, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38738117

RESUMO

Spontaneous rupture of the uterine artery is a rare and life-threatening cause of hemoperitoneum in pregnancy, associated with high maternal and perinatal morbidity and mortality. We present a case of a 29-year-old woman, in the 36th week of gestation, with acute abdomen due to hemoperitoneum. Ultrasound revealed free fluid in the abdominal cavity, with no signs of fetal distress, and the patient was mildly hypotensive. Exploratory laparotomy and cesarean section were performed, and extensive blood clots on the upper abdominal quadrants were discovered, as well as a bleeding left uterine artery. We expect that this case raises awareness of the ruptured uterine artery as a possible etiology of hemoperitoneum during pregnancy.

8.
Acta Med Port ; 37(7-8): 518-525, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38447018

RESUMO

INTRODUCTION: Uterine compressive sutures are conservative measures applied in cases of severe postpartum hemorrhage unresponsive to uterotonics. Pereira's suture was introduced in 2005 and consists of two longitudinal and three transverse non-transfixes sutures. Previous studies reported favorable results, highlighting its benefits and value. The aim of this study was to assess the efficacy, complications, and impact on fertility and future pregnancies of Pereira's suture applied in cases of uterine atony and postpartum hemorrhage. METHODS: An observational retrospective study was performed by consulting the medical records of women treated with Pereira's compressive sutures in a tertiary center between January 2013 and December 2022. We registered demographic data, pregnancy outcomes, short-term complications, and outcomes of subsequent pregnancies. RESULTS: A total of 50 women were treated with Pereira's suture. The overall success rate was 96% and no hysterectomies were performed. Women who had sutures performed during an intra-cesarean section had better outcomes than those who had an after-cesarean section. Complications were reported in 12% (n = 6) of women, with the most frequent being pelvic infection (n = 3) and abdominal pain (n = 3). Regarding fertility, all women desiring a future pregnancy (n = 5) were able to conceive, resulting in three live births. CONCLUSION: Pereira's suture is a type of suture that provides numerous advantages and should be considered when first-line medical treatment fails. When applied at an early stage, the sutures may prevent maternal morbidity. The Alcides Pereira's suture is a safe technique and appears to preserve fertility.


Assuntos
Hemorragia Pós-Parto , Técnicas de Sutura , Inércia Uterina , Humanos , Feminino , Estudos Retrospectivos , Adulto , Gravidez , Inércia Uterina/cirurgia , Resultado do Tratamento , Cesárea/efeitos adversos , Resultado da Gravidez , Adulto Jovem , Suturas
9.
Water Res ; 253: 121273, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38359597

RESUMO

The presence of biofilms in drinking water distribution systems (DWDS) is responsible for water quality deterioration and a possible source of public health risks. Different factors impact the biological stability of drinking water (DW) in the distribution networks, such as the presence and concentration of nutrients, water temperature, pipe material composition, hydrodynamic conditions, and levels of disinfectant residual. This review aimed to evaluate the current state of knowledge on strategies for DW biofilm disinfection through a qualitative and quantitative analysis of the literature published over the last decade. A systematic review method was performed on the 562 journal articles identified through database searching on Web of Science and Scopus, with 85 studies selected for detailed analysis. A variety of disinfectants were identified for DW biofilm control such as chlorine, chloramine, UV irradiation, hydrogen peroxide, chlorine dioxide, ozone, and others at a lower frequency, namely, electrolyzed water, bacteriophages, silver ions, and nanoparticles. The disinfectants can impact the microbial communities within biofilms, reduce the number of culturable cells and biofilm biomass, as well as interfere with the biofilm matrix components. The maintenance of an effective residual concentration in the water guarantees long-term prevention of biofilm formation and improves the inactivation of detached biofilm-associated opportunistic pathogens. Additionally, strategies based on multi-barrier processes by optimization of primary and secondary disinfection combined with other water treatment methods improve the control of opportunistic pathogens, reduce the chlorine-tolerance of biofilm-embedded cells, as well as decrease the corrosion rate in metal-based pipelines. Most of the studies used benchtop laboratory devices for biofilm research. Even though these devices mimic the conditions found in real DWDS, future investigations on strategies for DW biofilm control should include the validity of the promising strategies against biofilms formed in real DW networks.


Assuntos
Biofilmes , Desinfetantes , Desinfecção , Água Potável , Purificação da Água , Biofilmes/efeitos dos fármacos , Água Potável/microbiologia , Desinfecção/métodos , Desinfetantes/farmacologia , Purificação da Água/métodos , Abastecimento de Água , Microbiologia da Água
10.
Cureus ; 16(1): e53138, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38420071

RESUMO

Opsoclonus-ataxia paraneoplastic syndrome (OAPS) is a rare neurological disorder often associated with malignancies. This case report highlights an unusual instance of OAPS linked to a yolk sac (germ cell) tumor, a correlation underrepresented in the medical literature. The patient presented with distinct neurological symptoms alongside mediastinal lymphadenopathies. The subsequent diagnostic journey revealed a yolk sac germ cell tumor. Following incisional biopsies and treatment, the patient experienced fluctuations in mental status, leading to challenges in initiating chemotherapy. Despite these complications, a multidisciplinary approach involving neurologists, oncologists, and hematologists was pivotal. The case emphasizes the complexities of managing OAPS in tandem with a germ cell tumor, underscoring the need for further research and highlighting the significance of specialized neurological evaluation in similar cases.

11.
J Chem Phys ; 159(23)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38099555

RESUMO

Deep eutectic solvents (DESs) emerged as potential alternative solvent media in multiple areas, including biomolecular (cryo)preservation. Herein, we studied the stability of a small protein (ubiquitin) in water and a betaine-glycerol-water (B:G:W) (1:2:ζ; ζ = 0, 1, 2, 5, 10) DES, through molecular dynamics. An AMBER-based model that accurately describes the density and shear viscosity of the DES is proposed. We find that water molecules are largely trapped in the solvent, precluding the formation of a full hydration layer, seemingly opposite to osmolytes' preferential exclusion/preferential hydration mechanism. Although the protein is stable in the DES, structural fluctuations are largely suppressed and only recovered upon sufficient hydration. This is explained by a solvent-slaving mechanism where ß-fluctuations are key, with the non-monotonic hydration of some amino acids with the water content providing an explanation to the non-monotonic folding of some proteins in aqueous DESs. A major thermal stability enhancement in the DES is also observed, caused by a similar slowdown of the backbone torsional dynamics. Our results support a kinetic stabilization of the protein in the DES, whereas a possible thermodynamic stabilization does not follow a preferential hydration or water entrapment mechanism.


Assuntos
Solventes Eutéticos Profundos , Água , Solventes/química , Água/química , Glicerol/química , Proteínas/química , Estabilidade Proteica
12.
J Microbiol Biol Educ ; 24(3)2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38107998

RESUMO

Shake flask cultivation is a routine technique in microbiology and biotechnology laboratories where cell growth can be affected by the hydrodynamic conditions, which depend on the agitation velocity, shaking diameter, and shake flask size. Liquid agitation is implemented inherently to increase aeration, substrate transfer to the cells, and prevent sedimentation, disregarding the role of hydrodynamics in microbial growth and metabolism. Here, we present a simple approach to help standardize the hydrodynamic forces in orbital shakers to increase the experimental accuracy and reproducibility and give students a better knowledge of the significance of the agitation process in microbial growth.

13.
Cancers (Basel) ; 15(19)2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37835528

RESUMO

The approval of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) has remarkably improved the survival outcomes of patients with advanced hormone receptor-positive (HR+) breast cancer (BC), becoming the new standard of care treatment in these patients. Despite the efficacy of this therapeutic combination, intrinsic and acquired resistance inevitably occurs and represents a major clinical challenge. Several mechanisms associated with resistance to CDK4/6i have been identified, including both cell cycle-related and cell cycle-nonspecific mechanisms. This review discusses new insights underlying the mechanisms of action of CDK4/6i, which are more far-reaching than initially thought, and the currently available evidence of the mechanisms of resistance to CDK4/6i in BC. Finally, it highlights possible treatment strategies to improve CDK4/6i efficacy, summarizing the most relevant clinical data on novel combination therapies involving CDK4/6i.

14.
Cureus ; 15(9): e45672, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37745737

RESUMO

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is a frequently diagnosed neoplasm, which is typically managed with transurethral resection of bladder tumor (TURBT) eventually followed by intravesical therapies. Bacillus Calmette-Guérin (BCG) is used as first-line adjuvant treatment in high- (HR) and intermediate-risk (IR) NMIBC, although, in the latter, mitomycin C (MMC) may also be used. Multiple limitations to the use of BCG encouraged the search for therapeutic alternatives. In this context, hyperthermic intravesical chemotherapy with MMC (HIVEC-MMC) emerged as a promising therapy in the adjuvant setting for NMIBC. The aim of our study was to evaluate the tolerability, compliance, and survival outcomes of HIVEC-MMC in patients with IR- and HR-NMIBC. MATERIAL AND METHODS: This was a single-center retrospective analysis of IR- and HR- NMIBC patients who received HIVEC-MMC after TURBT between August 2018 and August 2022. Levels of risk stratification were defined using the European Association of Urology (EAU) criteria. The protocol consisted of four weekly HIVEC-MMC instillations (induction) followed by six monthly instillations (maintenance). The primary outcomes were to evaluate the tolerability and compliance with the HIVEC-MMC protocol and secondary outcomes were disease-free survival (DFS) and overall survival (OS). For the purpose of statistical analysis, methods of descriptive statistics, survival analysis (Kaplan-Meier estimation), and multivariate analysis (Cox regression, and binary logistic regression) were used. RESULTS: Fifty-seven patients were enrolled with a median age of 67.9 (34.4-83.5) years old. In this cohort, 40 patients (70.2%) had primary tumors. At the time of referral for HIVEC-MMC, the majority of the patients had IR-NMIBC (n= 33, 57.9%). A total of 41 patients (71.9%) completed the HIVEC-MMC protocol. Disease recurrence and adverse events (AEs) were the most common reasons to stop the protocol. After a median follow-up of 31 months (95% CI, 5.0-54.0), 32 patients (61.4%) were disease-free, 22 (38.6%) experienced recurrent disease and six patients (10.5%) died, although only one death was directly attributable to bladder cancer. The median DFS was 42 months (95% CI, 28.0-56.0). Completion of the HIVEC-MMC maintenance phase protocol stood as a predictive factor for DFS (44 months, 95% CI 29.1-58.9 vs. 14 months, 95% CI 0.0-29.6, p < 0.001; HR 4.48, 95% CI 1.65-12.15). The median OS was not reached; the 24- and 48-month OS were 92.6% and 82.7%, respectively. EAU risk group, ECOG-PS, and completion of HIVEC protocol were found to be significant predictive factors of OS but lost their significance on multivariate analysis. However, if we exclude those who experienced recurrence during the maintenance phase protocol, treatment completion had a significant positive impact on OS (HR: 42.8, 95% CI 1.75-1045.072, p= 0.021). CONCLUSIONS: Our study suggests that HIVEC is a secure and well-tolerated treatment with promising efficacy data, making this therapeutic approach a feasible option in IR- and HR-NMIBC patients, mainly in those who cannot tolerate or have contraindications to BCG therapy, but also as an alternative during BCG shortages.

15.
Sci Total Environ ; 905: 167332, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37758132

RESUMO

Among different pollutants of emerging concern, parabens have gained rising interest due to their widespread detection in water sources worldwide. This occurs because parabens are used in personal care products, pharmaceuticals, and food, in which residues are generated and released into aquatic environments. The regulation of the use of parabens varies across different geographic regions, resulting in diverse concentrations observed globally. Concentrations of parabens exceeding 100 µg/L have been found in wastewater treatment plants and surface waters while drinking water (DW) sources typically exhibit concentrations below 6 µg/L. Despite their low levels, the presence of parabens in DW is a potential exposure route for humans, raising concerns for both human health and environmental microbiota. Although a few studies have reported alterations in the functions and characteristics of microbial communities following exposure to emerging contaminants, the impact of the exposure to parabens by microbial communities, particularly biofilm colonizers, remains largely understudied. This review gathers the most recent information on the occurrence of parabens in water sources, as well as their effects on human health and aquatic organisms. The interactions of parabens with microbial communities are reviewed for the first time, filling the knowledge gaps on the effects of paraben exposure on microbial ecosystems and their impact on disinfection tolerance and antimicrobial resistance, with potential implications for public health.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Humanos , Parabenos/análise , Qualidade da Água , Ecossistema , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise
16.
J Hazard Mater ; 460: 132348, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37625295

RESUMO

The potential of pentapotassium bis(peroxymonosulphate) bis(sulphate) (OXONE) to control biofilms in drinking water distribution systems (DWDS) was evaluated and compared to chlorine disinfection. Mature biofilms of drinking water (DW)-isolated Stenotrophomonas maltophilia were formed using a simulated DWDS with a rotating cylinder reactor (RCR). After 30 min of exposure, OXONE at 10 × minimum bactericidal concentration (MBC) caused a significant 4 log reduction of biofilm culturability in comparison to the unexposed biofilms and a decrease in the number of non-damaged cells below the detection limit (4.8 log cells/cm2). The effects of free chlorine were restricted to approximately 1 log reduction in both biofilm culturability and non-damaged cells. OXONE in synthetic tap water (STW) at 25 ºC was more stable over 40 days than free chlorine in the same conditions. OXONE solution exhibited a disinfectant decrease of about 10% of the initial concentration during the first 9 days, and after this time the values remained stable. Whereas possible reaction of chlorine with inorganic and organic substances in STW contributed to free chlorine depletion of approximately 48% of the initial concentration. Electron paramagnetic resonance (EPR) spectroscopy studies confirmed the presence of singlet oxygen and other free radicals during S. maltophilia disinfection with OXONE. Overall, OXONE constitutes a relevant alternative to conventional DW disinfection for effective biofilm control in DWDS.


Assuntos
Água Potável , Stenotrophomonas maltophilia , Cloro , Halogênios , Biofilmes , Cloretos , Potássio
18.
Cell Rep Med ; 4(8): 101120, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37451269

RESUMO

The combination of endocrine therapy (ET) and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (CDK4/6i) was a hallmark in metastatic luminal breast cancer (BC). However, intrinsic and acquired resistance affects long-term efficacy. Here, we study the role of the receptor activator of nuclear factor-κB (RANK) pathway in CDK4/6i resistance. We find that RANK overexpression in luminal BC is associated with intrinsic resistance to CDK4/6i, both in vitro and in mouse xenografts, and decreased proliferation rate and chronic interferon (IFN) γ response are highlighted as resistance drivers. Gene expression data from the NeoPalAna CDK4/6i clinical trial, and studies with palbociclib-resistant cell lines, show that RANK is upregulated after treatment with CDK4/6i, supporting a role in acquired resistance. Our study shows that RANK ligand (RANKL) inhibitors can restore sensitivity to CDK4/6i and prevent acquired resistance. On the basis of these findings, we conclude that pharmacological inhibition of the RANK pathway through RANKL blocking could represent an add-on to ET + CDK4/6i, warranting further clinical studies.


Assuntos
Neoplasias da Mama , Transdução de Sinais , Humanos , Inibidores de Proteínas Quinases/farmacologia , Animais , Camundongos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Interferons/metabolismo
19.
Cureus ; 15(4): e37014, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37139023

RESUMO

Introduction Cancer patients on active treatment are at increased risk of developing coronavirus disease 2019 (COVID-19), making effective immunization of the utmost importance. However, the effectiveness of vaccination in this population is still unclear. This study aims to evaluate the response against COVID-19 in a cohort of patients with active cancer under immunosuppressive therapy. Methods This was a prospective, cross-sectional, single-center study that included patients with cancer under immunosuppressive therapy vaccinated against COVID-19 between April and September 2021. Exclusion criteria were: previous known severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, single-dose vaccine or incomplete vaccination scheme. Immunoglobulin G (IgG) anti-SARS-CoV-2 antibody levels were assessed using 35.2 binding antibody units (BAU)/mL as the positive cut-off. Assessments were performed 14-31 days after the first and second dose and three months after the second dose. Results A total of 103 patients were included. The median age was 60 years. Most patients were being treated for gastrointestinal cancer (n=38, 36.9%), breast cancer (n=33, 32%) or head and neck cancer (n=18, 17.5%). At evaluation, 72 patients (69.9%) were being treated with palliative intent. The majority were being treated with chemotherapy (CT) alone (57.3%). At the first assessment, levels of circulating SARS-CoV-2 IgG consistent with seroconversion were present in 49 patients (47.6%). At the time of the second assessment, 91% (n=100) achieved seroconversion. Three months after the second dose, 83% (n=70) maintained levels of circulating SARS-CoV-2 IgG consistent with seroconversion. In this study, no SARS-CoV-2 infection was reported in the study population. Conclusions Our findings suggest that this group of patients had a satisfactory COVID-19 immunization response. Although promising, this study should be replicated on a wider scale in order to validate these findings.

20.
Materials (Basel) ; 16(8)2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37109988

RESUMO

The Mg-Al-Zn-Ca system has demonstrated excellent flame resistance and mechanical properties in the as-cast condition. However, the potential of these alloys to be heat-treated, e.g., by aging, as well as the influence of the initial microstructure on the precipitation kinetics, is yet to be comprehensively explored. Ultrasound treatment was applied during the solidification of an AZ91D-1.5%Ca alloy to promote microstructure refinement. Samples from treated and non-treated ingots were subjected to solution treatment at 415 °C for 480 min, followed by aging at 175 °C for up to 4920 min. The results showed that the ultrasound-treated material could reach the peak-age condition in a shorter period than the non-treated one, suggesting accelerated precipitation kinetics and, thus, enhanced aging response. However, the tensile properties showed a decrease in the peak age compared to the as-cast condition, probably due to the formation of precipitates at the grain boundaries that promote the formation of microcracks and intergranular early fracture. This research shows that tailoring the material's as-cast microstructure may positively affect its aging response, shortening the heat treatment duration, thereby making the process less expensive and more sustainable.

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