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1.
ACS Nano ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32227914

RESUMO

Bioorthogonal activation of prodrugs provides a strategy for on-demand on-site production of therapeutics. Intracellular activation provides a strategy to localize therapeutics, poten-tially minimizing off-target effects. To this end, nanoparticles embedded with transition metal catalysts (nanozymes) were engineered to generate either 'hard' irreversible or 'soft' re-versible coronas in serum. The hard corona induced nanozyme aggregation, effectively inhibiting nanozyme activi-ty, whereas only modest loss of activity was observed with the non-aggregating soft corona nanozymes. In both cases complete activity was restored by treatment with proteases. Intracellular activity mirrored this reactivation: endogenous proteases in the endosome provided intracellular activation of both nanozymes. The role of intracellular proteases in nanozyme reactivation was verified through treatment of the cells with protease inhibitors, which prevented reactivation. This study demonstrates the use of intracellular proteolysis as a strategy for localization of therapeutic generation to within cells.

2.
World Neurosurg ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32229300

RESUMO

OBJECTIVE: The purpose of this report is to analyze the relationship between cognitive performance and white matter (WM) integrity in patients with temporal lobe epilepsy (TLE), in order to establish a radiologic criteria to help with patient selection for surgery. METHODS: Nineteen adults with TLE were included in the study. A tractography analysis of the fractional anisotropy (FA) and the mean diffusivity (MD) of the following fascicles were calculated: arcuate (AF), cingulum (CG), fornix (FORX), inferior frontooccipital (IFOF), inferior longitudinal (FLI), parahipocampal (PHC) and uncinate (UNC). The Wechsler Memory Scale-Third Edition (WMS-III) neuropsychological test was performed to evaluate short and long-term verbal (LM-I and II) and nonverbal (VR-I and II) memory. Relationships between memory scores and diffusion were calculated. RESULTS: Lower LM-I scores were correlated with lower MD of right-IFOF, while lower LM-II scores, were related to higher values of FA in bilateral CG, right-UF, right-PHC and lower MD in left-CG. Finally, lower values in VR-I scores were associated to lower values in MD in right-CG and IFOF. CONCLUSIONS: Structural changes of some WM tracts were associated with deterioration of both short and long-term memory. These alterations were more associated to verbal memory than to non-verbal memory. These changes mainly consist in an increase in FA and a decrease in MD; which could be interpreted as reorganization phenomena. DTI could be a useful tool for cognitive assessment in surgical candidates with TLE that are not suitable for neuropsychological testing, or in whom their results do not lead to definitive conclusions.

4.
Artigo em Espanhol | MEDLINE | ID: mdl-32245646

RESUMO

OBJECTIVE: Population ageing is a reality for which national health systems are not adapted. The World Health Organisation has already raised awareness about the implementation of specific measures, from undergraduate training to dedicated elderly care units, to tackle this situation. In this article, the aim is to analyse the potential benefits of geriatric monitoring on elderly neurosurgical patients. MATERIAL AND METHODS: A descriptive analysis was performed in this medical centre, comparing the information collected from elderly patients (over 75 years of age) admitted into the neurosurgical department during 2periods: June 2015 to February 2017, in which a shared geriatric monitoring was implemented, and between October 2013 and May 2015, equivalent period, in which only the geriatrician performed the evaluation of the patients' general condition, before referring them to other social-healthcare units. A number of factors were considered, including mean age, gender, the neurosurgical condition that led to admission, mean stay, infectious complications, acute confusional syndrome, admission into an intensive care unit, need for support from other medical departments, reoperations, mortality during hospitalisation, referral to social-health units, readmission within a month, and mortality within a year. RESULTS: A total of 173 patients on shared monitoring were compared to 189 patients from the previous period. Both groups had similar demographic characteristics. During the analysis, a significant reduction was observed in shared monitoring as regards, mean hospitalisation, infectious complications, admissions into an intensive care unit, the need for support from other medical departments, readmissions within a month, and mortality within a year. CONCLUSIONS: On patients of over 75 years of age, shared geriatric-neurosurgical monitoring reduces mean hospitalisation, morbidity, the need for support from other medical departments, early readmission, and mortality within a year. This strategy prioritises patient care, reduces costs, and rationalises resources.

5.
Sci Total Environ ; 721: 137734, 2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32179346

RESUMO

Plastic pollution is a global problem with great local and regional variability. Plastic litter reaches beaches directly and indirectly through different pathways, due to both terrestrial and marine pressures. In this study, we assess and characterize meso and microplastic pollution on four Uruguayan oceanic beaches along a gradient of tourist use within a complex regional coastal marine system. In Punta del Diablo we found a total mean density of 106 items m-2 of different debris (pellets, fragments, and foams) with different polymeric compositions, and diverse persistent bioaccumulative and toxic chemicals (PAHs, PCBs, OCs, heavy metals). However, the trend of plastic debris densities along this gradient was not what was expected. Fabeiro, one of the sites furthest from the urban center, had the highest total mean density of plastics (292 items m-2) suggesting that marine influences (winds, currents, and beach orientation) have a preponderant role in the distribution of micro and mesoplastics. Meanwhile, the density in the urban site (Pueblo) was highest during summer (March, 201 items m-2), 200 times higher than the density observed in winter (July, 1 item m-2). Although this difference could be associated to the peak season (southern summer), the analysis of types of plastics (171 pellets m-2 vs. 8 cigarette butts m-2) suggested a predominance of marine inputs. Seasonal changes in the configuration of the beaches due to natural geomorphological dynamics imply alternating states (Source or Sink of debris) that also affect the final density of plastics in the system. The relative importance of both sources is highly variable throughout the year and understanding them may directly improve beach management and stranded coastal plastic litter cleaning.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32198205

RESUMO

Competence allows bacteria to internalize exogenous DNA fragments for the acquisition of new phenotypes such as antibiotic resistance or virulence traits. In most streptococci, competence is regulated by ComRS signaling, a system based on the mature ComS pheromone (XIP), which is internalized to activate the (R)RNPP-type ComR sensor by triggering dimerization and DNA binding. Cross-talk analyses demonstrated major differences of selectivity between ComRS systems and raised questions concerning the mechanism of pheromone-sensor recognition and coevolution. Here, we decipher the molecular determinants of selectivity of the closely related ComRS systems from Streptococcus thermophilus and Streptococcus vestibularis Despite high similarity, we show that the divergence in ComR-XIP interaction does not allow reciprocal activation. We perform the structural analysis of the ComRS system from S. vestibularis. Comparison with its ortholog from S. thermophilus reveals an activation mechanism based on a toggle switch involving the recruitment of a key loop by the XIP C terminus. Together with a broad mutational analysis, we identify essential residues directly involved in peptide binding. Notably, we generate a ComR mutant that displays a fully reversed selectivity toward the heterologous pheromone with only five point mutations, as well as other ComR variants featuring XIP bispecificity and/or neofunctionalization for hybrid XIP peptides. We also reveal that a single XIP mutation relaxes the strictness of ComR activation, suggesting fast adaptability of molecular communication phenotypes. Overall, this study is paving the way toward the rational design or directed evolution of artificial ComRS systems for a range of biotechnological and biomedical applications.

7.
Asian J Androl ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32217836

RESUMO

Assisted reproductive technologies involving the use of spermatozoa and eggs for in vitro fertilization (IVF) have come as the solution for many infertile couples to become parents. However, in some cases, the use of ejaculated spermatozoa delivers poor IVF performance. Some studies have suggested the use of testicular spermatozoa in severe male infertility cases, but no guidelines regarding their utilization are currently available. In the present study, we found the mRNA protamine 1/protamine 2 (P1/P2) ratio to be a valuable biomarker of poor sperm function that could be used as a diagnostic key for the identification of cases that would benefit from the use of testicular spermatozoa. A total of 23 couples undergoing egg donation cycles with at least one previous cycle failure were studied. All couples underwent two consecutive intracytoplasmic sperm injection (ICSI) cycles with either ejaculated or testicular spermatozoa (TESA). The sperm mRNA P1/P2 ratio, fertilization rate, blastocyst rate, and pregnancy and live birth rate were compared. Results showed improved ICSI and clinical outcomes in cycles with testicular spermatozoa in men with altered mRNA P1/P2 ratios. TESA cycles presented significantly higher rates of fertilization (mean ± standard deviation: 76.1% ± 15.1% vs 65.5% ± 18.8%), blastocyst formation (55.0% ± 20.3% vs 30.8% ± 23.8%), and good morphological quality blastocyst (28.9% ± 22.9% vs 13.5% ± 17.9%) and also improvements on pregnancy (60.9% vs 0%) and healthy birth rates (56.5% vs 0%) than EJACULATE cycles. The results described here suggest that in patients with previous IVF/ICSI failures and aberrant mRNA protamine ratios, the use of testicular spermatozoa may be a good alternative to improve clinical outcomes.

8.
PLoS One ; 15(2): e0229079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069319

RESUMO

AIM: To analyse i) the association of physical fitness during early second trimester and late pregnancy with maternal and neonatal outcomes; and ii) to investigate whether physical fitness is associated with the type of birth (vaginal or caesarean section). METHODS: Pregnant women from the GESTAFIT Project (n = 159) participated in this longitudinal study. Maternal physical fitness including upper- and lower-body strength, cardiorespiratory fitness (CRF) and flexibility were measured through objective physical fitness tests at the 16th and 34th gestational weeks. Maternal and neonatal outcomes were collected from obstetric medical records. Umbilical arterial and venous blood gas pH and partial pressure of carbon dioxide (PCO2) and oxygen (PO2), were assessed. RESULTS: At the 16th week, greater upper-body muscle strength was associated with greater neonatal birth weight (r = 0.191, p<0.05). Maternal flexibility was associated with a more alkaline arterial pH (r = 0.220, p<0.05), higher arterial PO2 (r = 0.237, p<0.05) and lower arterial PCO2 (r = -0.331, p<0.01) in umbilical cord blood. Maternal CRF at the 16th gestational week was related to higher arterial umbilical cord PO2 (r = 0.267, p<0.05). The women who had caesarean sections had lower CRF (p<0.001) at the 16th gestational week and worse clustered overall physical fitness, both at the 16th (-0.227, p = 0.003, confidence interval (CI): -0.376, -0.078) and 34th gestational week (-0.223; p = 0.018; CI: -0.432, -0.015) compared with the women who had vaginal births. CONCLUSION: Increasing physical fitness during pregnancy may promote better neonatal outcomes and is associated with a decrease in the risk of caesarean section. This trial was registered at ClinicalTrials.gov (NCT02582567) on October 20, 2015.

9.
Nutrients ; 12(2)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32024036

RESUMO

: We hypothesized that curcumin may mitigate muscle protein degradation and loss through attenuation of proteolytic activity in limb muscles of mice exposed to reloading (7dR) following immobilization (7dI). In gastrocnemius of mice (female C57BL/6J, 10 weeks) exposed to recovery following a seven-day period of hindlimb immobilization with/without curcumin treatment, markers of muscle proteolysis (systemic troponin-I), atrophy signaling pathways and histone deacetylases, protein synthesis, and muscle phenotypic characteristics and function were analyzed. In gastrocnemius of reloading mice compared to unloaded, muscle function, structure, sirtuin-1, and protein synthesis improved, while proteolytic and signaling markers (FoxO1/3) declined. In gastrocnemius of unloaded and reloaded mice treated with curcumin, proteolytic and signaling markers (NF-kB p50) decreased and sirtuin-1 activity and hybrid fibers size increased (reloaded muscle), while no significant improvement was seen in muscle function. Treatment with curcumin elicited a rise in sirtuin-1 activity, while attenuating proteolysis in gastrocnemius of mice during reloading following a period of unloading. Curcumin attenuated muscle proteolysis probably via activation of histone deacetylase sirtuin-1, which also led to decreased levels of atrophy signaling pathways. These findings offer an avenue of research in the design of therapeutic strategies in clinical settings of patients exposed to periods of disuse muscle atrophy.

10.
J Neuroeng Rehabil ; 17(1): 12, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005265

RESUMO

BACKGROUND: There is a clinical need to identify diagnostic parameters that objectively quantify and monitor the effective visual ability of patients with homonymous visual field defects (HVFDs). Visual processing speed (VPS) is an objective measure of visual ability. It is the reaction time (RT) needed to correctly search and/or reach for a visual stimulus. VPS depends on six main brain processing systems: auditory-cognitive, attentional, working memory, visuocognitive, visuomotor, and executive. We designed a new assessment methodology capable of activating these six systems and measuring RTs to determine the VPS of patients with HVFDs. METHODS: New software was designed for assessing subject visual stimulus search and reach times (S-RT and R-RT respectively), measured in seconds. Thirty-two different everyday visual stimuli were divided in four complexity groups that were presented along 8 radial visual field positions at three different eccentricities (10o, 20o, and 30o). Thus, for each HVFD and control subject, 96 S- and R-RT measures related to VPS were registered. Three additional variables were measured to gather objective data on the validity of the test: eye-hand coordination mistakes (ehcM), eye-hand coordination accuracy (ehcA), and degrees of head movement (dHM, measured by a head-tracker system). HVFD patients and healthy controls (30 each) matched by age and gender were included. Each subject was assessed in a single visit. VPS measurements for HFVD patients and control subjects were compared for the complete test, for each stimulus complexity group, and for each eccentricity. RESULTS: VPS was significantly slower (p < 0.0001) in the HVFD group for the complete test, each stimulus complexity group, and each eccentricity. For the complete test, the VPS of the HVFD patients was 73.0% slower than controls. They also had 335.6% more ehcMs, 41.3% worse ehcA, and 189.0% more dHMs than the controls. CONCLUSIONS: Measurement of VPS by this new assessment methodology could be an effective tool for objectively quantifying the visual ability of HVFD patients. Future research should evaluate the effectiveness of this novel method for measuring the impact that any specific neurovisual rehabilitation program has for these patients.

11.
Toxicol Sci ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32110797

RESUMO

Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted low-molecular weight iron-siderophore binding protein. NGAL overexpression in injured tubular epithelia partly explain its utility as a sensitive and early urinary biomarker of acute kidney injury (AKI). Herein, we extend mechanistic insights into the source and kinetics of urinary NGAL excretion in experimental AKI. Three models of experimental AKI were undertaken in adult male Wistar rats; renal ischemia-reperfusion injury (IRI) and gentamicin (G) and cisplatin (Cisp) nephrotoxicity. Alongside standard histological and biochemical assessment of AKI, urinary NGAL excretion rate, plasma NGAL concentration and renal NGAL mRNA/protein expression were assessed. In situ renal perfusion studies were undertaken to discriminate direct shedding of NGAL to the urine from addition of NGAL to the urine secondary to alterations in the tubular handling of glomerular filtrate derived protein. Renal NGAL expression and urinary excretion increased in experimental AKI. In acute studies in both the IRI and G models, direct renal perfusion with Kreb's buffer eliminated urinary NGAL excretion. Addition of exogenous NGAL to the Kreb's buffer circuit, reestablishment of perfusion with systemic blood or reperfusion with renal vein effluent restored high levels of urinary NGAL excretion. Urinary NGAL excretion in AKI arises in large proportion from reduced reabsorption from the glomerular filtrate. Hence, sub-clinical cellular dysfunction could increase urinary NGAL, particularly in concert with elevations in circulating pre-renal NGAL and/or pharmacological inhibition of tubular reabsorption. More granular interpretation of urinary NGAL measurements could optimise the scope of its clinical utility as a biomarker of AKI.

12.
Sensors (Basel) ; 20(4)2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32075172

RESUMO

Water management is paramount in countries with water scarcity. This also affects agriculture, as a large amount of water is dedicated to that use. The possible consequences of global warming lead to the consideration of creating water adaptation measures to ensure the availability of water for food production and consumption. Thus, studies aimed at saving water usage in the irrigation process have increased over the years. Typical commercial sensors for agriculture irrigation systems are very expensive, making it impossible for smaller farmers to implement this type of system. However, manufacturers are currently offering low-cost sensors that can be connected to nodes to implement affordable systems for irrigation management and agriculture monitoring. Due to the recent advances in IoT and WSN technologies that can be applied in the development of these systems, we present a survey aimed at summarizing the current state of the art regarding smart irrigation systems. We determine the parameters that are monitored in irrigation systems regarding water quantity and quality, soil characteristics and weather conditions. We provide an overview of the most utilized nodes and wireless technologies. Lastly, we will discuss the challenges and the best practices for the implementation of sensor-based irrigation systems.

14.
J Control Release ; 320: 96-104, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31931052

RESUMO

Current therapies fail to eradicate colorectal Cancer Stem Cells (CSCs). One of the proposed reasons for this failure is the selection, by chemotherapy exposure, of resistant cells responsible for tumor recurrence. In this regard, CXCR4 overexpression in tumor associates with resistance and poor prognosis in colorectal cancer (CRC) patients. In this study, the effectiveness of engineered CXCR4-targeted self-assembling toxin nanoparticles has been explored in the selective killing of CXCR4+ human colon-CSCs compared to 5-Fluorouracil and Oxaliplatin, both classical CRC chemotherapeutic agents. To assess this, 3D spheroid colon-CSCs cultures directly derived from CRC patients and CRC-CSC spheroid-derived tumor mouse models were developed. In these animal models, nanostructured toxins show highly selective induction of pyroptosis in the absence of apoptosis, thus having a great potential to overcome tumor resistance, since the same tumor models show resistance to chemotherapeutics. Results set the basis for further development of more efficient therapies focused on selective CXCR4+ CSCs elimination activating non-apoptotic mechanisms and represent a pre-clinical proof of concept for the use of CSCs-targeted nanostructured toxins as protein drugs for CRC therapy.

15.
Neuroendocrinology ; : 1-32, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31991407

RESUMO

BACKGROUND: Galectin-1 (Gal-1) plays major roles in cancer by modulating different processes leading to tumor development and progression. In the last years, it has been suggested as a promising target for anticancer therapy. Recently, aflibercept has shown high affinity for Gal-1. Here, we investigated how aflibercept could exert its antitumor activity via Gal-1-driven pathways in neuroendocrine carcinomas (NEC). METHODS AND RESULTS: NEC tumor xenograft were used to assess the effect of aflibercept on Gal-1 functions. Aflibercept induced a significant reduction of Gal-1 at epithelial, stromal and extracellular localizations in lung NEC, whereas this was not observed in colon NECs which displayer low expression of Gal-1. Additionally, aflibercept significantly reduced p-VEGFR2 protein, extracellular matrix remodeling, epithelial-mesenchymal transition and activation of cancer-associated fibroblast hampering cell invasion in lung NEC but not in colon NEC. Gal-1 screening in human NECs confirmed that pulmonary and pancreatic tumors displayed higher levels of Gal-1 than colon NECs, becoming good candidates to benefit from aflibercept treatment. CONCLUSIONS: The lack of validated predictive markers of aflibercept is a weakness for guaranteeing the best treatment management with this drug. This work provides new mechanistic insight of aflibercept depending on Gal-1. Thus, in tumors overexpressing Gal-1 aflibercept has not only an antiangiogenic effect but also prevents Gal-1-mediated tumor-stroma crosstalk. The stronger aflibercept effect in tumors with high levels of Gal-1 points out this protein as a molecular marker to predict the efficacy of this agent not only for NECs but also for other tumors with high levels of this protein.

16.
Astrobiology ; 20(3): 405-414, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31985262

RESUMO

The aim of the European Space Agency's ExoMars rover mission is to search for potential traces of present or past life in the swallow subsurface (2 m depth) of Mars. The ExoMars rover mission relies on a suite of analytical instruments envisioned to identify organic compounds with biological value (biomarkers) associated with a mineralogical matrix in a highly oxidative environment. We investigated the feasibility of detecting basic organics (linear and branched lipid molecules) with Raman laser spectroscopy, an instrument onboard the ExoMars rover, when exposed to oxidant conditions. We compared the detectability of six lipid molecules (alkanes, alkanols, fatty acid, and isoprenoid) before and after an oxidation treatment (15 days with hydrogen peroxide), with and without mineral matrix support (amorphous silica rich vs. iron rich). Raman and infrared spectrometry was combined with gas chromatography-mass spectrometry to determine detection limits and technical constraints. We observed different spectral responses to degradation depending on the lipid molecule and mineral substrate, with the silica-rich material showing better preservation of organic signals. These findings will contribute to the interpretation of Raman laser spectroscopy results on cores from the ExoMars rover landing site, the hydrated silica-enriched delta fan on Cogoon Vallis (Oxia Planum).

17.
Eur J Pediatr ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31993775

RESUMO

There is a lack of consensus on quality indicators suitable for neonatal transport. The aim of this study is to make a proposal for specific quality indicators for newborn transport. A retrospective descriptive study was performed (2009 to 2015) where twenty-four indicators were selected, evaluated and classified according to the 6 dimensions of quality of the Institute of Medicine. Among the 24 evaluated quality metrics, there were 3 of them which needed a correction when evaluating neonatal transport performance, because they were significantly correlated with gestational age. They were (a) stabilisation time, (b) prevalence of newborn arterial hypotension (defined by gestational age) and (c) unnoticed hypothermia at referral hospital.Conclusion: Quality evaluation through the definition of specific metrics in newborn transport is feasible. These indicators should be defined or adjusted for newborn population to measure the actual performance of the transport service.What is Known:• Quality indicators may help in defining metrics for clinical practice, promoting benchmarking and defining areas of improvement.• Newborn characteristics call for a specialised care, and quality measure during newborn transport require specific metrics. Quality metrics for paediatric transport have been defined using Delphi method. Some of these measures need to be specific for newborn, due to their intrinsic characteristics.What is New:• Using evidence-based literature and our newborn transport experience, specific quality indicators for newborn transport are suggested.• Data analysis shows how some indicators need to be adjusted for gestational age.

18.
Astrobiology ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31916858

RESUMO

Sulfate and iron oxide deposits in Río Tinto (Southwestern Spain) are a terrestrial analog of early martian hematite-rich regions. Understanding the distribution and drivers of microbial life in iron-rich environments can give critical clues on how to search for biosignatures on Mars. We simulated a robotic drilling mission searching for signs of life in the martian subsurface, by using a 1m-class planetary prototype drill mounted on a full-scale mockup of NASA's Phoenix and InSight lander platforms. We demonstrated fully automated and aseptic drilling on iron and sulfur rich sediments at the Río Tinto riverbanks, and sample transfer and delivery to sterile containers and analytical instruments. As a ground-truth study, samples were analyzed in the field with the life detector chip immunoassay for searching microbial markers, and then in the laboratory with X-ray diffraction to determine mineralogy, gas chromatography/mass spectrometry for lipid composition, isotope-ratio mass spectrometry for isotopic ratios, and 16S/18S rRNA genes sequencing for biodiversity. A ubiquitous presence of microbial biomarkers distributed along the 1m-depth subsurface was influenced by the local mineralogy and geochemistry. The spatial heterogeneity of abiotic variables at local scale highlights the importance of considering drill replicates in future martian drilling missions. The multi-analytical approach provided proof of concept that molecular biomarkers varying in compositional nature, preservation potential, and taxonomic specificity can be recovered from shallow drilling on iron-rich Mars analogues by using an automated life-detection lander prototype, such as the one proposed for NASA's IceBreaker mission proposal.

19.
Urol Int ; : 1-8, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31962327

RESUMO

OBJECTIVES: Recurrent urinary tract infections (R-UTIs) are very common amongst women, and alternatives to antibacterial prophylaxis are necessary. This study evaluates the effectiveness of a sublingual bacterial vaccine for the prophylaxis of R-UTIs. METHODS: We conducted a quasi-experimental pretest-posttest study of 166 women diagnosed with R-UTIs. Both before and after the start of treatment with the vaccine, we analysed the total number of R-UTI episodes, the urine culture results, and the type and number of antibiotic packages consumed. Symptoms and urine cultures were evaluated 3, 6, 9, 12, 18, and 24 months after initiating treatment with the vaccine. RESULTS: The mean time of follow-up after vaccination was 1.7 years. After vaccination, there was a 54.6% reduction in episodes of UTI, and a 56.2% reduction in positive urine cultures. At 3 months, 74.4% of the patients had no R-UTI, the rate falling to 68.1% at 6 months, 52.4% at 12 months, and 44.5% at 24 months. The cumulative probability of maintaining negative urine cultures was 76% at 3 months, 37% at 12 months, and 18% at 2 years. CONCLUSIONS: The use of a sublingual bacterial vaccine for the prophylaxis of R-UTIs in women is an effective treatment that contributes to a reduction in the number of UTI episodes.

20.
Anal Chem ; 92(2): 2011-2018, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31825199

RESUMO

Nanomaterial-based drug delivery vehicles are able to deliver therapeutics in a controlled, targeted manner. Currently, however, there are limited analytical methods that can detect both nanomaterial distributions and their biochemical effects concurrently. In this study, we demonstrate that matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI) can be used together to obtain nanomaterial distributions and biochemical consequences. These studies employ nanoparticle-stabilized capsules (NPSCs) loaded with siRNA as a testbed. MALDI-MSI experiments on spleen tissues from intravenously injected mice indicate that NPSCs loaded with anti-TNF-α siRNA cause changes to the lipid composition in white pulp regions of the spleen, as anticipated, based on pathways known to be affected by TNF-α, whereas NPSCs loaded with scrambled siRNA do not cause the predicted changes. Interestingly, LA-ICP-MSI experiments reveal that the NPSCs primarily localize in the red pulp, suggesting that the observed changes in lipid composition are due to diffusive rather than localized effects on TNF-α production. Such information is only accessible by combining data from the two modalities, which we accomplish by using the heme signals from MALDI-MSI and iron signals from LA-ICP-MSI to overlay the images. Several unexpected changes in lipid composition also occur in regions where the NPSCs are found, suggesting that the NPSCs themselves can influence tissue biochemistry as well.

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