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1.
Sci Rep ; 14(1): 8594, 2024 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615154

RESUMO

Mixed forests play a fundamental ecological role increasing biodiversity and providing ecosystem services; it has been suggested they have higher resilience and resistance against disturbances, particularly fire. Here, we compare tree mortality in post-fire mixed and pure stands in Spain, on 2,782 plots and 30,239 trees during the period 1986 to 2007. We show evidence that mixed stands can have higher post-fire mortality than pure stands, and specific mixtures of species with different fire-related strategies increase the stand's vulnerability to fire damage versus pure stands of either species, such is the case of Pinus halepensis-Pinus nigra mixtures. Mixtures of two species often had higher mortality than species growing in pure stands. Combinations of species with different fire-related strategies can both enhance or reduce forest resistance. The role and management of mixed forests should be reconsidered after these findings, in order to enhance forest resilience to fires.


Assuntos
Ecossistema , Pinus , Florestas , Árvores , Biodiversidade
2.
J Biomed Mater Res A ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38623028

RESUMO

Diabetic foot ulcers are a serious complication of uncontrolled diabetes, emphasizing the need to develop wound healing strategies that are not only effective but also biocompatible, biodegradable, and safe. We aimed to create biomatrices composed of semi-interpenetrated polymer networks of collagen, polyurethane, and dextran, to enhance the wound healing process. The hydrogels were extensively characterized by various analytical techniques, including analysis of their structure, crystallinity, thermal properties, gelation process, reticulation, degradation, cell proliferation, and healing properties, among others. Semi-interpenetrated hydrogels containing dextran at levels of 10%, 20%, and 30% exhibited porous interconnections between collagen fibers and entrapped dextran granules, with a remarkable crosslinking index of up to 94% promoted by hydrogen bonds. These hydrogels showed significant improvements in mechanical properties, swelling, and resistance to proteolytic and hydrolytic degradation. After 24 h, there was a significant increase in the viability of several cell types, including RAW 264.7 cells, human peripheral blood mononuclear cells, and dermal fibroblasts. In addition, these hydrogels demonstrated an increased release of interleukin-10 and transforming growth factor-beta1 while inhibiting the release of monocyte chemotactic protein-1 and tumor necrosis factor-alpha after 72 h. Furthermore, these hydrogels accelerated the wound healing process in diabetic rats after topical application. Notably, the biomaterial with 20% dextran (D20) facilitated wound closure in only 21 days. These results highlight the potential of the D20 hydrogel, which exhibits physicochemical and biological properties that enhance wound healing by inhibiting inflammation and fibrillogenesis while remaining safe for application to the skin.

3.
Data Brief ; 54: 110384, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38646195

RESUMO

Process-based forest models combine biological, physical, and chemical process understanding to simulate forest dynamics as an emergent property of the system. As such, they are valuable tools to investigate the effects of climate change on forest ecosystems. Specifically, they allow testing of hypotheses regarding long-term ecosystem dynamics and provide means to assess the impacts of climate scenarios on future forest development. As a consequence, numerous local-scale simulation studies have been conducted over the past decades to assess the impacts of climate change on forests. These studies apply the best available models tailored to local conditions, parameterized and evaluated by local experts. However, this treasure trove of knowledge on climate change responses remains underexplored to date, as a consistent and harmonized dataset of local model simulations is missing. Here, our objectives were (i) to compile existing local simulations on forest development under climate change in Europe in a common database, (ii) to harmonize them to a common suite of output variables, and (iii) to provide a standardized vector of auxiliary environmental variables for each simulated location to aid subsequent investigations. Our dataset of European stand- and landscape-level forest simulations contains over 1.1 million simulation runs representing 135 million simulation years for more than 13,000 unique locations spread across Europe. The data were harmonized to consistently describe forest development in terms of stand structure (dominant height), composition (dominant species, admixed species), and functioning (leaf area index). Auxiliary variables provided include consistent daily climate information (temperature, precipitation, radiation, vapor pressure deficit) as well as information on local site conditions (soil depth, soil physical properties, soil water holding capacity, plant-available nitrogen). The present dataset facilitates analyses across models and locations, with the aim to better harness the valuable information contained in local simulations for large-scale policy support, and for fostering a deeper understanding of the effects of climate change on forest ecosystems in Europe.

4.
Molecules ; 29(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38474584

RESUMO

The integration of clean energy generation with wastewater treatment holds promise for addressing both environmental and energy concerns. Focusing on photocatalytic hydrogen production and wastewater treatment, this study introduces PdIn/TiO2 catalysts for the simultaneous removal of the pharmaceutical contaminant paracetamol (PTM) and hydrogen production. Physicochemical characterization showed a high distribution of Pd and In on the support as well as a high interaction with it. The Pd and In deposition enhance the light absorption capability and significantly improve the hydrogen evolution reaction (HER) in the absence and presence of paracetamol compared to TiO2. On the other hand, the photoelectroxidation of PTM at TiO2 and PdIn/TiO2 follows the full mineralization path and, accordingly, is limited by the adsorption of intermediate species on the electrode surface. Thus, PdIn-doped TiO2 stands out as a promising photoelectrocatalyst, showcasing enhanced physicochemical properties and superior photoelectrocatalytic performance. This underscores its potential for both environmental remediation and sustainable hydrogen production.

5.
Viruses ; 16(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38543797

RESUMO

Torque Teno Virus (TTV) is a nonpathogenic and ubiquitous ssDNA virus, a member of the Anelloviridae family. TTV has been postulated as a biomarker in transplant patients. This study aimed to determine the TTV species diversity and variability in renal transplant recipients and to associate species diversity with the corresponding TTV viral load. From 27 recipients, 30 plasma samples were selected. Viral load was determined using two real-time PCR assays, followed by RCA-NGS and ORF1 phylogenetic analysis. The TTV diversity was determined in all samples. Variability was determined in three patients with two sequential samples (pre- and post-transplantation). Most of the samples presented multiple TTV species, up to 15 different species were detected. In the pre-transplant samples (n = 12), the most prevalent species were TTV3 (75%) and TTV13 (75%), and the median number of species per sample was 5 (IQR: 4-7.5). TTV3 was also the most prevalent (56%) in the post-transplant samples (n = 18), and the median number of species was 2 (IQR: 1.8-5.5). No significant correlation between the number of species and viral load was found. The number and type of TTV species showed total variability over time. We report high TTV species diversity in Argentinian recipients, especially in pre-transplant period, with total intra-host variability. However, we found no significant correlation between this high diversity and TTV viral load.


Assuntos
Infecções por Vírus de DNA , Transplante de Rim , Torque teno virus , Humanos , Torque teno virus/genética , Transplante de Rim/efeitos adversos , Filogenia , Transplantados , Carga Viral , DNA Viral/genética
6.
BMC Oral Health ; 24(1): 229, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38350956

RESUMO

OBJECTIVE: The main objective of this study was to estimate the prevalence of molar incisor hypomineralisation (MIH), an alteration of tooth enamel with an estimated worldwide prevalence rate of 14%, among children using primary care services in the Community of Madrid, Spain. MATERIALS AND METHODS: This was a descriptive, cross-sectional and multicentre study. After calibrating all researchers and following the diagnostic criteria of the European Academy of Paediatric Dentistry (EAPD), children aged between 8 and 16 years who were users of the dental services at 8 primary oral health units of the Madrid Health Service (SERMAS) were included. The children underwent a dental examination, and the parents were asked to complete a questionnaire. RESULTS: The prevalence of MIH was 28.63% (CI: 24.61-32.65%). The age cohorts most affected by MIH were 8 years (21.4%) and 11 years (20.7%). The presence of MIH was greater among girls (85; 60.71%) than among boys (55; 39.28%). The mean number of affected teeth per patient was 4.46 ± 2.8. The most frequently affected molar was the upper right first molar (74.3%), and the upper left central incisor was the most affected incisor (37.85%). Opacities were the defects most frequently recorded (63.57%). CONCLUSIONS: The prevalence of MIH in this study is the highest of all relevant studies conducted in Spain.


Assuntos
Hipoplasia do Esmalte Dentário , Hipomineralização Molar , Criança , Masculino , Feminino , Humanos , Adolescente , Hipoplasia do Esmalte Dentário/epidemiologia , Estudos Transversais , Prevalência , Esmalte Dentário
7.
mBio ; 15(3): e0310523, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349183

RESUMO

Understanding the evolutionary dynamics of foodborne pathogens throughout our food production chain is of utmost importance. In this study, we reveal that Salmonella Typhimurium can readily and reproducibly acquire vastly increased heat shock resistance upon repeated exposure to heat shock. Counterintuitively, this boost in heat shock resistance was invariantly acquired through loss-of-function mutations in the dnaJ gene, encoding a heat shock protein that acts as a molecular co-chaperone of DnaK and enables its role in protein folding and disaggregation. As a trade-off, however, the acquisition of heat shock resistance inevitably led to attenuated growth at 37°C and higher temperatures. Interestingly, loss of DnaJ also downregulated the activity of the master virulence regulator HilD, thereby lowering the fraction of virulence-expressing cells within the population and attenuating virulence in mice. By connecting heat shock resistance evolution to attenuation of HilD activity, our results confirm the complex interplay between stress resistance and virulence in Salmonella Typhimurium. IMPORTANCE: Bacterial pathogens such as Salmonella Typhimurium are equipped with both stress response and virulence features in order to navigate across a variety of complex inhospitable environments that range from food-processing plants up to the gastrointestinal tract of its animal host. In this context, however, it remains obscure whether and how adaptation to one environment would obstruct fitness in another. In this study, we reveal that severe heat stress counterintuitively, but invariantly, led to the selection of S. Typhimurium mutants that are compromised in the activity of the DnaJ heat shock protein. While these mutants obtained massively increased heat resistance, their virulence became greatly attenuated. Our observations, therefore, reveal a delicate balance between optimal tuning of stress response and virulence features in bacterial pathogens.


Assuntos
Proteínas de Bactérias , Salmonella typhimurium , Animais , Camundongos , Salmonella typhimurium/genética , Virulência/genética , Temperatura , Proteínas de Bactérias/metabolismo , Resposta ao Choque Térmico , Proteínas de Choque Térmico/metabolismo , Chaperonas Moleculares/metabolismo
8.
Acta Paediatr ; 113(4): 716-721, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38186235

RESUMO

AIM: The architecture of neonatal units plays a key role in developmental strategies and preterm outcomes. The aim was to evaluate the design of Spanish neonatal units and its impact on the participation of parents in neonatal care. METHODS: A web-based survey was sent to all level III Spanish neonatal units, including questions about hospital data, architectural design, facilities and family participation. RESULTS: The study included 63 units. Most units (87%) had part or all the intensive care patients located in open bay units, while 54% had at least one individual patient cubicle. Single family rooms, defined as those including enough space and furniture for family members to stay with the infant without restrictions, were available in 8 units (13%). Eighteen units (29%) had a structured programme of family education. Units with single family rooms were more likely to have parental participation in rounds (p < 0.01), safety protocols (p = 0.02), oxygen management (p < 0.01) and nasogastric tube feeding (p = 0.02), as well as to allow siblings to participate in kangaroo care (p < 0.01). CONCLUSION: Widely variable architectural designs and policies were found in Spanish neonatal units. The presence of single family rooms may have impacted the participation of parents in neonatal care.


Assuntos
Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Recém-Nascido , Lactente , Humanos , Espanha , Pais , Inquéritos e Questionários
9.
Appl Microbiol Biotechnol ; 108(1): 38, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38175235

RESUMO

Emergence of genetic variants with increased resistance/tolerance to natural antimicrobials, such as essential oils, has been previously evidenced; however, it is unknown whether mutagenesis follows a general or a specific pattern. For this purpose, we carried out four adaptive laboratory evolutions (ALE) in parallel of Salmonella enterica Typhimurium with carvacrol. After 10 evolution steps, we selected and characterized one colony from each lineage (SeCarA, SeCarB, SeCarC, and SeCarD). Phenotypic characterization of the four evolved strains revealed enhanced survival to lethal treatments; two of them (SeCarA and SeCarB) showed an increase of minimum inhibitory concentration of carvacrol and a better growth fitness in the presence of carvacrol compared to wild-type strain. Whole genome sequencing revealed 10 mutations, of which four (rrsH, sseG, wbaV, and flhA) were present in more than one strain, whereas six (nirC, fliH, lon, rob, upstream yfhP, and upstream argR) were unique to individual strains. Single-mutation genetic constructs in SeWT confirmed lon and rob as responsible for the increased resistance to carvacrol as well as to antibiotics (ampicillin, ciprofloxacin, chloramphenicol, nalidixic acid, rifampicin, tetracycline, and trimethoprim). wbaV played an important role in increased tolerance against carvacrol and chloramphenicol, and flhA in cross-tolerance to heat treatments. As a conclusion, no common phenotypical or genotypical pattern was observed in the isolated resistant variants of Salmonella Typhimurium emerged under carvacrol stress. Furthermore, the demonstration of cross-resistance against heat and antibiotics exhibited by resistant variants raises concerns regarding food safety. KEY POINTS: • Stable resistant variants of Salmonella Typhimurium emerged under carvacrol stress • No common pattern of mutagenesis after cyclic exposures to carvacrol was observed • Resistant variants to carvacrol showed cross-resistance to heat and to antibiotics.


Assuntos
Antibacterianos , Salmonella typhimurium , Salmonella typhimurium/genética , Antibacterianos/farmacologia , Cloranfenicol , Cimenos
10.
bioRxiv ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36798157

RESUMO

In defiance of the paradigm that calories from all sources are equivalent, we and others have shown that dietary protein is a dominant regulator of healthy aging. The restriction of protein or the branched-chain amino acid isoleucine promotes healthspan and extends lifespan when initiated in young or adult mice. However, many interventions are less efficacious or even deleterious when initiated in aged animals. Here, we investigate the physiological, metabolic, and molecular consequences of consuming a diet with a 67% reduction of all amino acids (Low AA), or of isoleucine alone (Low Ile), in male and female C57BL/6J.Nia mice starting at 20 months of age. We find that both diet regimens effectively reduce adiposity and improve glucose tolerance, which were benefits that were not mediated by reduced calorie intake. Both diets improve specific aspects of frailty, slow multiple molecular indicators of aging rate, and rejuvenate the aging heart and liver at the molecular level. These results demonstrate that Low AA and Low Ile diets can drive youthful physiological and molecular signatures, and support the possibility that these dietary interventions could help to promote healthy aging in older adults.

11.
Transplant Cell Ther ; 30(2): 187.e1-187.e12, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38000709

RESUMO

Plasma biomarkers of endothelial dysfunction have been postulated for the diagnosis and prognosis of acute graft-versus-host disease (aGVHD). However, their use is not validated in clinical practice yet. The endothelial activation and stress index (EASIX), a simple score based on routine laboratory parameters, is considered to be an indirect marker of endothelial damage. High value of EASIX was correlated with worse non-relapse mortality (NRM) and overall survival (OS) and a high risk of sinusoidal obstructive syndrome and transplant-associated thrombotic microangiopathy (TA-TMA). This study investigates the predictive value of plasma biomarkers and the EASIX score for the prediction of aGVHD. We assessed vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor receptor 1 (TNFR1), and VWF:Ag plasma levels and the EASIX score before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and on days 0, 3, 7, 14, and 21 in an experimental cohort (n = 33). EASIX was transformed to a base-2 logarithm to perform the analysis. For the most relevant biomarkers, we estimate the optimal cutoff values and the discriminatory ability to differentiate patients with high-risk of aGVHD. The conclusions obtained in the experimental cohort were validated in a large cohort of 321 patients at the same institution. Plasma biomarkers and EASIX showed similar post-transplantation dynamics consisting of a progressive increase. Multivariate analysis showed an association between high TNFR1 levels and Log-2 EASIX score on day 7 after transplantation with an increased likelihood of developing aGVHD (hazard ratio [HR] = 1, P = .002; HR = 2.31, P = .013, respectively). Patients with TNFR1 ≥1300 ng/mL (HR = 7.19, P = .006) and Log2-EASIX ≥3 (HR = 14.7, P <.001) at day 7 after transplantation were more likely to develop aGVHD with high predictive accuracy (C-index of 74% and 81%, respectively). In the validation cohort, patients with Log2-EASIX ≥3 on day 7 after transplantation presented a significantly higher incidence of grade II-IV aGVHD (HR = 1.94, P = .004) independent of GVHD prophylaxis (HR = 0.38, P = .004), conditioning regimen (HR = 0.59, P =.02) and type of donor (HR = 2.38, P = .014). Differential degree of endothelial damage can be measured using both EASIX score and plasma biomarkers in the early post-transplantation period. Patients at risk of developing aGVHD could be easily identified by a high EASIX score. Both indicators of endothelial activation represent a promising approach to predict aGVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Receptores Tipo I de Fatores de Necrose Tumoral , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Biomarcadores
12.
Environ Pollut ; 341: 122683, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37827356

RESUMO

Nanoscale zero-valent iron (nZVI) is a promising material tool for the remediation of metal(loid)-contaminated soils since it reduces metal(loid) availability and plant uptake, thereby enhancing the development of the plants. However, the effects of nZVI as nanoparticles on soil properties, plants, and the microbial rhizosphere in unpolluted soils are poorly understood. Here we tested the impact of nZVI at different doses (0.5 and 5% of commercial suspension) on soil properties, lettuce plants, and their microbial rhizosphere in two non-contaminated soils with distinct physico-chemical properties (alkaline versus acidic soil). To this end, a pot experiment was performed with lettuce plants in a growth chamber for a month. Both soils showed an increase in of pH and available Fe after nZVI application. However, these effects were more marked in the acidic soil. In this regard, the plants in this soil showed increased biomass and Fe content. TEM analysis revealed that although the roots and leaves of plants grown in the alkaline soil showed better cell integrity than those in acidic soil-an observation that was consistent with the visual appearance of the plants-the former were more affected by the nZVI treatment. Regarding the microbial rhizosphere, in general, nZVI enhanced enzyme activity regardless of the soil type. Microbial functional diversity showed a significant decline in response to nZVI in alkaline soil. In contrast, the 0.5% nZVI treatment had a positive effect on this parameter in acidic soil. Bacterial genetic diversity was less affected by the presence of nZVI than fungal diversity, which was higher in nZVI-treated acidic soils. In addition, alterations of bacterial and fungal communities were associated with available Fe in acidic soil. In conclusion, soil properties play a key role in determining the effects of nZVI on lettuce plants and their rhizosphere.


Assuntos
Recuperação e Remediação Ambiental , Poluentes do Solo , Ferro/química , Solo/química , Rizosfera , Poluentes do Solo/análise
13.
Clin Transl Sci ; 17(1): e13698, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38140786

RESUMO

Tramadol is an important minor opioid prescribed for pain management. In this study, we analyzed the well-known impact of CYP2D6 genetic variation and 60 additional variants in eight candidate genes (i.e., ABCG2, SLCO1B1, CYP2D6, CYP2B6, CYP2C19, CYP2C9, CYP3A5, and CYP3A4) on tramadol efficacy and safety. Some 108 patients with pain after surgery admitted to a post-anesthesia care unit (PACU) and prescribed tramadol were recruited. They were genotyped, and tramadol M1/M2 metabolite concentrations were determined by a newly validated HPLC-MS/MS method. CYP2D6 intermediate (IM) and poor (PM) metabolizers showed lower M1 concentrations adjusted for dose/weight at 30 and 120 min compared to ultrarapid (UM) and normal (NM) metabolizers (univariate p < 0.001 and 0.020, multivariate p < 0.001 and 0.001, unstandardized ß coefficients = 0.386 and 0.346, R2 = 0.146 and 0.120, respectively). CYP2B6 PMs (n = 10) were significantly related to a higher reduction in pain 30 min after tramadol intake (univariate p = 0.038, multivariate p = 0.016, unstandardized ß coefficient = 0.224, R2 = 0.178), to lower PACU admission time (p = 0.007), and to lower incidence of adverse drug reactions (p = 0.038) compared to the other phenotypes. CYP3A4 IMs and PMs showed a higher prevalence of drowsiness and dizziness (p = 0.028 and 0.005, respectively). Our results suggest that the interaction of CYP2B6 and CYP2D6 phenotypes may be clinically relevant, pending validation of these results in large, independent cohorts. Additional research is required to clarify the impact of CYP3A4 genetic variation on tramadol response.


Assuntos
Citocromo P-450 CYP2D6 , Tramadol , Humanos , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP2B6/genética , Espectrometria de Massas em Tandem , Analgésicos Opioides , Fenótipo , Genótipo , Dor Pós-Operatória , Transportador 1 de Ânion Orgânico Específico do Fígado/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-38071552

RESUMO

OBJECTIVE: To systematically review and meta-analyse the effect of late surfactant administration versus placebo in reducing the incidence of death or bronchopulmonary dysplasia (BPD) in preterm infants. DESIGN: PubMed, EMBASE, CINAHL and Cochrane CENTRAL were searched until 30 May 2023, for randomised controlled trials (RCTs) comparing administration of surfactant after 48 hours of age versus placebo in preterm ventilator-dependent neonates. The primary outcome was incidence of death or BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes included incidence of BPD at 36 weeks PMA, pre-discharge mortality, use of postnatal steroids, post-discharge respiratory support, treatment with steroids or hospitalisation prior to 1-year corrected age. RESULTS: Pooled analyses of four RCTs (N=850) showed no statistically significant difference between groups in the incidence of death or BPD at 36 weeks' PMA (relative risk (RR) 0.99; 95% CI 0.90 to 1.10; Grades of Recommendation, Assessment, Development and Evaluation (GRADE): moderate). Late surfactant administration significantly decreased the need for post-discharge respiratory support prior to 1-year corrected age (two RCTs; N=522; RR 0.72; 95% CI 0.59 to 0.89; GRADE: low). Other secondary outcomes did not differ significantly between the groups. CONCLUSIONS: Administration of late surfactant does not improve the rates of death or BPD at 36 weeks when administered to preterm infants with prolonged respiratory insufficiency. Additional adequately powered trials are needed to establish the efficacy of late surfactant therapy in preterm infants. PROSPERO REGISTRATION NUMBER: CRD42023432463.

15.
J Pers Med ; 13(11)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-38003881

RESUMO

Tadalafil and finasteride are used in combination for the management of benign prostatic hyperplasia (BPH). Genetic variations in genes involved in the metabolism and transport of tadalafil or finasteride (i.e., pharmacogenes) could affect their pharmacokinetic processes altering their drug exposure, efficacy, and toxicity. The main objective of this study was to investigate the effects of variants in pharmacogenes on the pharmacokinetics of tadalafil and finasteride. An exploratory candidate gene study involving 120 variants in 33 genes was performed with 66 male healthy volunteers from two bioequivalence clinical trials after administration of tadalafil/finasteride 5 mg/5 mg under fed or fasting conditions. Afterwards, a confirmatory study was conducted with 189 male and female volunteers receiving tadalafil 20 mg formulations in seven additional bioequivalence clinical trials. Regarding tadalafil, fed volunteers showed higher area in the time-concentration curve (AUC∞), maximum plasma concentration (Cmax), and time to reach Cmax (tmax) compared to fasting volunteers; male volunteers also showed higher AUC∞ and Cmax compared to female volunteers. Furthermore, fed volunteers presented higher finasteride AUC∞, Cmax and tmax compared to fasting individuals. Variants in ABCC3, CYP1A2, CES1, NUDT15, SLC22A1/A2 and UGT2B10 were nominally associated with pharmacokinetic variation in tadalafil and/or finasteride but did not remain significant after correction for multiple comparisons. Genetic variation did not demonstrate to clinically impact on the pharmacokinetics of finasteride and tadalafil; however, additional studies with larger sample sizes are needed to assess the effect of rare variants, such as CYP3A4*20 or *22, on tadalafil and finasteride pharmacokinetics.

16.
Sci Rep ; 13(1): 20316, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37985732

RESUMO

Floods are among the most destructive extreme events that exist, being the main cause of people affected by natural disasters. In the near future, estimated flood intensity and frequency are projected to increase. In this context, automatic and accurate satellite-derived flood maps are key for fast emergency response and damage assessment. However, current approaches for operational flood mapping present limitations due to cloud coverage on acquired satellite images, the accuracy of flood detection, and the generalization of methods across different geographies. In this work, a machine learning framework for operational flood mapping from optical satellite images addressing these problems is presented. It is based on a clouds-aware segmentation model trained in an extended version of the WorldFloods dataset. The model produces accurate and fast water segmentation masks even in areas covered by semitransparent clouds, increasing the coverage for emergency response scenarios. The proposed approach can be applied to both Sentinel-2 and Landsat 8/9 data, which enables a much higher revisit of the damaged region, also key for operational purposes. Detection accuracy and generalization of proposed model is carefully evaluated in a novel global dataset composed of manually labeled flood maps. We provide evidence of better performance than current operational methods based on thresholding spectral indices. Moreover, we demonstrate the applicability of our pipeline to map recent large flood events that occurred in Pakistan, between June and September 2022, and in Australia, between February and April 2022. Finally, the high-resolution (10-30m) flood extent maps are intersected with other high-resolution layers of cropland, building delineations, and population density. Using this workflow, we estimated that approximately 10 million people were affected and 700k buildings and 25,000 km[Formula: see text] of cropland were flooded in 2022 Pakistan floods.

17.
Sci Rep ; 13(1): 19999, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978332

RESUMO

Methane is the second most important greenhouse gas contributor to climate change; at the same time its reduction has been denoted as one of the fastest pathways to preventing temperature growth due to its short atmospheric lifetime. In particular, the mitigation of active point-sources associated with the fossil fuel industry has a strong and cost-effective mitigation potential. Detection of methane plumes in remote sensing data is possible, but the existing approaches exhibit high false positive rates and need manual intervention. Machine learning research in this area is limited due to the lack of large real-world annotated datasets. In this work, we are publicly releasing a machine learning ready dataset with manually refined annotation of methane plumes. We present labelled hyperspectral data from the AVIRIS-NG sensor and provide simulated multispectral WorldView-3 views of the same data to allow for model benchmarking across hyperspectral and multispectral sensors. We propose sensor agnostic machine learning architectures, using classical methane enhancement products as input features. Our HyperSTARCOP model outperforms strong matched filter baseline by over 25% in F1 score, while reducing its false positive rate per classified tile by over 41.83%. Additionally, we demonstrate zero-shot generalisation of our trained model on data from the EMIT hyperspectral instrument, despite the differences in the spectral and spatial resolution between the two sensors: in an annotated subset of EMIT images HyperSTARCOP achieves a 40% gain in F1 score over the baseline.

19.
Food Technol Biotechnol ; 61(3): 357-377, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38022877

RESUMO

Tailor-made foods, also known as foods with programmable properties, are specialised systems with unique composition prepared by different methods, using the known mechanisms of action of their bioactive ingredients. The development of tailor-made foods involves the evaluation of individual components, including bioactive substances derived from waste products of other productions, such as essential oils. These components are evaluated both individually and in combination within food compositions to achieve specific functionalities. This review focuses on the application of minimal processing technologies for the production and preservation of tailor-made foods. It examines a range of approaches, including traditional and emerging technologies, as well as novel ingredients such as biomolecules from various sources and microorganisms. These approaches are combined according to the principles of hurdle technology to achieve effective synergistic effects that enhance food safety and extend the shelf life of tailor-made foods, while maintaining their functional properties.

20.
Int J Mol Sci ; 24(20)2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37894954

RESUMO

Drug combination therapy is the most common pharmacological strategy for hypertension management. No pharmacogenetic biomarkers for guiding hypertension pharmacotherapy are available to date. The study population were 64 volunteers from seven bioequivalence trials investigating formulations with valsartan, olmesartan and/or hydrochlorothiazide. Every volunteer was genotyped for 10 genetic variants in different transporters' genes. Additionally, valsartan-treated volunteers were genotyped for 29 genetic variants in genes encoding for different metabolizing enzymes. Variability in pharmacokinetic parameters such as maximum concentration (Cmax) and time to reach it (tmax), the incidence of adverse drug reactions (ADRs) and blood pressure measurements were analyzed as a function of pharmacogenetic and demographic parameters. Individuals with the ABCB1 rs1045642 T/T genotype were associated with a higher valsartan tmax compared to those with T/G and G/G genotypes (p < 0.001, ß = 0.821, R2 = 0.459) and with a tendency toward a higher postural dizziness incidence (11.8% vs. 0%, p = 0.070). A higher hydrochlorothiazide dose/weight (DW)-corrected area under the curve (AUC∞/DW) was observed in SLC22A1 rs34059508 G/A volunteers compared to G/G volunteers (p = 0.050, ß = 1047.35, R2 = 0.051), and a tendency toward a higher postural dizziness incidence (50% vs. 1.6%, p = 0.063). Sex impacted valsartan and hydrochlorothiazide pharmacokinetics, showing a lower exposure in women, whereas no significant differences were found for olmesartan pharmacokinetics.


Assuntos
Hidroclorotiazida , Hipertensão , Humanos , Feminino , Valsartana/efeitos adversos , Hidroclorotiazida/efeitos adversos , Tontura/induzido quimicamente , Tontura/tratamento farmacológico , Tetrazóis/efeitos adversos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Hipertensão/induzido quimicamente , Variação Genética , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacocinética
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