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Menopausal women may experience symptoms of depression, sometimes even progressing clinical depression requiring treatment to improve quality of life. While varying levels of estrogen in perimenopause may contribute to an increased biological vulnerability to mood disturbances, the effectiveness of estrogen replacement therapy (ERT) in the relief of depressive symptoms remains controversial. Menopausal depression has a complex, multifactorial etiology, that has limited the identification of optimal treatment strategies for the management of this psychiatric complaint. Nevertheless, clinical evidence increasingly supports the notion that estrogen exerts neuroprotective effects on brain structures related to mood regulation. Indeed, research using preclinical animal models continues to improve our understanding of menopause and the effectiveness of ERT and other substances at treating depression-like behaviors. However, questions regarding the efficacy of ERT in perimenopause have been raised. These questions may be answered by further investigation using specific animal models of reduced ovarian function. This review compares and discusses the advantages and pitfalls of different models emulating the menopausal stages and their relationship with the onset of depressive-like signs, as well as the efficacy and mechanisms of conventional and novel ERTs in treating depressive-like behavior. Ovariectomized young rats, middle-to-old aged intact rats, and females treated with reprotoxics have all been used as models of menopause, with stages ranging from surgical menopause to perimenopause. Additionally, this manuscript discusses the impact of organistic and therapeutic variables that may improve or reduce the antidepressant response of females to ERT. Findings from these models have revealed the complexity of the dynamic changes occurring in brain function during menopausal transition, reinforcing the idea that the best approach is timely intervention considering the opportunity window, in addition to the careful selection of treatment according to the presence or absence of reproductive tissue. Additionally, data from animal models has yielded evidence to support new promising estrogens that could be considered as ERTs with antidepressant properties and actions in endocrine situations in which traditional ERTs are not effective.
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In the Mexican Caribbean, environmental changes, hydrometeorological events, and anthropogenic activities promote dynamism in the coastal vegetation cover associated with the dune; however, their pace and magnitude remain uncertain. Using Landsat 7 imagery, spatial and temporal changes in coastal dune vegetation were estimated for the 2011-2020 period in the Sian Ka'an Biosphere Reserve. The SAVI index revealed cover changes at different magnitudes and paces at the biannual, seasonal, and monthly timeframes. Climatic seasons had a significant influence on vegetation cover, with increases in cover during northerlies (SAVI: p = 0.000), while the topographic profile of the dune was relevant for structure. Distance-based multiple regressions and redundancy analysis showed that temperature had a significant effect (p < 0.05) on SAVI patterns, whereas precipitation showed little influence (p > 0.05). The Mann-Kendall tendency test indicated high dynamism in vegetation loss and recovery with no defined patterns, mostly associated with anthropogenic disturbance. High-density vegetation such as mangroves, palm trees, and shrubs was the most drastically affected, although a reduction in bare soil was also recorded. This study demonstrated that hydrometeorological events and climate variability in the long term have little influence on vegetation dynamism. Lastly, it was observed that anthropogenic activities promoted vegetation loss and transitions; however, the latter were also linked to recoveries in areas with pristine environments, relevant for tourism.
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Fasciolosis, a globally re-emerging zoonotic disease, is mostly caused by the parasitic infection with Fasciola hepatica, often known as the liver fluke. This disease has a considerable impact on livestock productivity. This study aimed to evaluate the fluke burdens and faecal egg counts in goats that were administered phage clones of cathepsin L mimotopes and then infected with F. hepatica metacercariae. Additionally, the impact of vaccination on the histology of the reproductive system, specifically related to egg generation in adult parasites, was examined. A total of twenty-four goats, which were raised in sheds, were divided into four groups consisting of six animals each. These groups were randomly assigned. The goats were then subjected to two rounds of vaccination. Each vaccination involved the administration of 1 × 1013 phage particles containing specific mimotopes for cathepsin L2 (group 1: PPIRNGK), cathepsin L1 (group 2: DPWWLKQ), and cathepsin L1 (group 3: SGTFLFS). The immunisations were carried out on weeks 0 and 4, and the Quil A adjuvant was used in combination with the mimotopes. The control group was administered phosphate-buffered saline (PBS) (group 4). At week 6, all groups were orally infected with 200 metacercariae of F. hepatica. At week 22 following the initial immunisation, the subjects were euthanised, and adult F. hepatica specimens were retrieved from the bile ducts and liver tissue, and subsequently quantified. The specimens underwent whole-mount histology for the examination of the reproductive system, including the testis, ovary, vitellaria, Mehlis' gland, and uterus. The mean fluke burdens following the challenge were seen to decrease by 50.4%, 62.2%, and 75.3% (p < 0.05) in goats that received vaccinations containing cathepsin L2 PPIRNGK, cathepsin L1 DPWWLKQ, and cathepsin L1 SGTFLFS, respectively. Animals that received vaccination exhibited a significant reduction in the production of parasite eggs. The levels of IgG1 and IgG2 isotypes in vaccinated goats were significantly higher than in the control group, indicating that protection is associated with the induction of a mixed Th1/Th2 immune response. The administration of cathepsin L to goats exhibits a modest level of efficacy in inducing histological impairment in the reproductive organs of liver flukes, resulting in a reduction in egg output.
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Catepsina L , Fasciola hepatica , Fasciolíase , Cabras , Vacinação , Animais , Fasciola hepatica/imunologia , Catepsina L/metabolismo , Fasciolíase/veterinária , Fasciolíase/prevenção & controle , Fasciolíase/imunologia , Fasciolíase/parasitologia , Vacinação/métodos , Feminino , Masculino , Doenças das Cabras/parasitologia , Doenças das Cabras/prevenção & controle , Doenças das Cabras/imunologia , Contagem de Ovos de Parasitas , Bacteriófagos/imunologiaRESUMO
This study rigorously investigates the effectiveness of nonlinear filters in CMOS for 2-D signal processing to enhance image quality. We comprehensively compare traditional linear filters' performance, which operate on the principle of linearity, with nonlinear filters, such as the median-median (Med-Med) approach, designed to handle nonlinear data. To ensure the validity of our findings, we use widely accepted metrics like normalized squared error (NSE), peak signal-to-noise ratio (PSNR), and structural similarity index (SSIM) to quantify the differences. Our simulations and experiments, conducted under controlled conditions, demonstrate that nonlinear filters in CMOS outperform linear filters in removing impulse noise and enhancing images. We also address the challenges of implementing these algorithms at the hardware level, focusing on power consumption and chip area optimization. Additionally, we propose a new architecture for the Med-Med filter and validate its functionality through experiments using a 9-pixel image sensor array. Our findings highlight the potential of nonlinear filters in CMOS for real-time image quality enhancement and their applicability in various real-world imaging applications. This research contributes to visual technology by combining theoretical insights with practical implementations, paving the way for more efficient and adaptable imaging systems.
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The pollution caused by petroleum-derived plastic materials has become a major environmental problem that has encouraged the development of new compostable and environmentally friendly materials for food packaging based on biomodified polymers with household residues. This study aims to design, synthesize, and characterize a biobased polymeric microstructure film from polyvinyl alcohol and chitosan reinforced with holocellulose from spent coffee grounds for food-sustainable packaging. Chemical isolation with a chlorite-based solution was performed to obtain the reinforced holocellulose from the spent coffee ground, and the solvent casting method was used to obtain the films to study. Physicochemical and microscopic characterizations were conducted to identify and select the best formulations using a simplex-centroid design analysis. The response surface methodology results indicate that the new packaging material obtained with equal amounts of polymers and reinforced material (1:1:1) possesses the appropriate barrier properties and microstructural character to prevent water attack and hydrophobic behavior and thus could be used as an alternative for food packaging materials.
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Quitosana , Café , Embalagem de Alimentos , Álcool de Polivinil , Embalagem de Alimentos/métodos , Café/química , Quitosana/química , Álcool de Polivinil/química , Celulose/química , Biopolímeros/química , Interações Hidrofóbicas e HidrofílicasRESUMO
In this work, we experimentally analyzed and demonstrated the performance of an in-line Mach-Zehnder interferometer in the visible region, with an LED light source. The different waist diameter taper and asymmetric core-offset interferometers proposed used a single-mode fiber (SMF). The visibility achieved was V = 0.14 with an FSR of 23 nm for the taper MZI structure and visibilities of V = 0.3, V = 0.27, and V = 0.34 with FSRs of 23 nm, 17 nm, and 8 nm and separation lengths L of 2.5 cm, 4.0 cm, and 5.0 cm between the core-offset structure, respectively. The experimental investigation of the response to the temperature sensor yielded values from 50 °C to 300 °C; the sensitivity obtained was 3.53 a.u./°C, with R2 of 0.99769 and 1% every 1 °C in the transmission. For a range of 50 °C to 150 °C, 20.3 pm/°C with a R2 of 0.96604 was obtained.
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To mitigate the environmental impact of microplastics (MPs), the scientific community has innovated sustainable and biodegradable polymers as viable alternatives to traditional plastics. Chitosan, the deacetylated form of chitin, stands as one of the most thoroughly investigated biopolymers and has garnered significant interest due to its versatile applications in both medical and cosmetic fields. Nevertheless, there is still a knowledge gap regarding the impact that chitosan biopolymer films (CBPF) may generate in aquatic organisms. In light of the foregoing, this study aimed to assess and compare the potential effects of CBPF on the gastrointestinal tract, gills, brain, and liver of Danio rerio against those induced by MPs. The findings revealed that both CBPF and MPs induced changes in the levels of oxidative stress biomarkers across all organs. However, it is essential to note that our star plots illustrate a tendency for CBPF to activate antioxidant enzymes and for MPs to produce oxidative damage. Regarding gene expression, our findings indicate that MPs led to an up-regulation in the expression of genes associated with apoptotic response (p53, casp3, cas9, bax, and bcl2) in all fish organs. Meanwhile, CBPF produced the same effect in genes related to antioxidant response (nrf1 and nrf2). Overall, our histological observations substantiated these effects, revealing the presence of plastic particles and tissue alterations in the gills and gastrointestinal tract of fish subjected to MPs. From these results, it can be concluded that CBPF does not represent a risk to fish after long exposure.
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Quitosana , Microplásticos , Estresse Oxidativo , Poliestirenos , Poluentes Químicos da Água , Peixe-Zebra , Animais , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Quitosana/química , Estresse Oxidativo/efeitos dos fármacos , Poliestirenos/toxicidade , Biopolímeros , EcotoxicologiaRESUMO
Introduction: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes. Methods: To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity). Results: According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02). Discussion: Our data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.
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COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , COVID-19/genética , Serina Proteases , SARS-CoV-2 , Estudos TransversaisRESUMO
We present the design, fabrication and discuss the performance of a new combined high-resolution Scanning Tunneling and Thermopower Microscope (STM/SThEM). We also describe the development of the electronic control, the user interface, the vacuum system, and arrangements to reduce acoustical noise and vibrations. We demonstrate the microscope's performance with atomic-resolution topographic images of highly oriented pyrolytic graphite (HOPG) and local thermopower measurements in the semimetal Bi2Te3. Our system offers a tool to investigate the relationship between electronic structure and thermoelectric properties at the nanoscale.
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OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.
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Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Masculino , Feminino , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Espanha , Anticorpos Monoclonais/uso terapêutico , Adulto , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Quimioterapia de Consolidação , Antígeno B7-H1/antagonistas & inibidoresRESUMO
Abstract Introduction: The red starfish (Echinaster sepositus) is one of the most common asteroid species in the Mediterranean Sea. However, information about their biology or their role in benthic communities is scarce. Objective: This study aims to provide new information on the ecology of this species through the temporal characterization of the population of E. sepositus in Cala del Racó (Alicante, Spain) and the in situ monitoring of its reproductive cycle. Methods: For this purpose, three study areas were established at different depths. For each of the recorded starfish, data about the size, the substrate on which it was found, the area, the depth and the sex in the case of observing the reproduction were collected. Results: A total of 19 samplings have been carried out throughout a year of study. In this way, it has been possible to observe that the density of individuals increases in the shallower zone during autumn and winter, when the temperature drops to 14.13 ºC, while it decreases in spring and summer when the temperature rises to 27.17 ºC. Those results are reversed in the deepest part of the study. The highest density of individuals (0.51 ind/m2) occurred in October. Arborescent photophilic algae and crustose coralline algae were the substrates with the highest number of E. sepositus recorded. Medium to large specimens are located preferably on crustose coralline algae or arborescent photophilic algae, while smaller individuals were mostly located on Posidonia oceanica. No specimens of E. sepositus were observed spawning. Conclusions: Data leads to assume that there is a migration of starfishes towards more superficial areas when the water is at colder temperature and towards deeper areas when the temperature increases. It is valued the possibility that there is a change in the nutritional needs of E. sepositus throughout its development. According to our observations, the future reproduction studies should be concentrated between late-summer and early-autumn.
Resumen Introducción: La estrella de mar roja (Echinaster sepositus) es una de las especies de asteroideos más comunes del mar Mediterráneo. Sin embargo, la información sobre su biología o su papel en las comunidades bentónicas es escasa. Objetivo: Este estudio pretende aportar nueva información sobre la ecología de esta especie mediante la caracterización temporal de la población de E. sepositus en la Cala del Racó (Alicante, España) y el monitoreo in situ de su ciclo reproductivo. Métodos: Con este fin se establecieron tres zonas de estudio a distintas profundidades. Para cada una de las estrellas registradas se tomaron datos de tamaño, el sustrato sobre el que se encuentra, la zona, la profundidad y el sexo en caso de observar la reproducción. Resultados: A lo largo de un año de estudio se han realizado un total de 19 muestreos. De esta forma se ha podido observar que la densidad de individuos aumenta en la zona menos profunda durante otoño e invierno, cuando la temperatura del agua baja hasta los 14.13 ºC, mientras que se reduce en primavera y verano, cuando la temperatura se eleva hasta los 27.17 ºC. Este resultado se invierte en la zona más profunda del estudio. La mayor densidad de individuos ha sido observada en octubre (0.51 ind/m2). Las algas fotófilas arborescentes y las algas coralinales costrosas han sido los sustratos con un mayor número de E. sepositus registrados. Los ejemplares de tamaños medianos a grandes se localizan preferentemente sobre algas coralinales costrosas o algas fotófilas arborescentes, mientras que los individuos de menor tamaño se sitúan mayormente sobre Posidonia oceanica. No se observaron ejemplares de E. sepositus reproduciéndose. Conclusiones: Los datos permiten presuponer que existe una migración entre las zonas más superficiales, cuando la temperatura del agua es menor, y zonas más profundas cuando la temperatura aumenta. Se valora la posibilidad de la existencia de un cambio en los requerimientos nutricionales de E. sepositus a lo largo de su desarrollo. De acuerdo con nuestras observaciones, los estudios futuros sobre la reproducción de esta especie deben concentrarse entre finales de verano y principios de otoño.
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Animais , Reprodução , Estrelas-do-Mar/anatomia & histologia , Espanha , Estudos de AmostragemRESUMO
This work analyzes the role of the tight junction (TJ) protein ZO-2 on mechanosensation. We found that the lack of ZO-2 reduced apical membrane rigidity measured with atomic force microscopy, inhibited the association of γ-actin and JAM-A to the cell border, and instead facilitated p114RhoGEF and afadin accumulation at the junction, leading to an enhanced mechanical tension at the TJ measured by FRET, with a ZO-1 tension probe, and increased tricellular TJ tension. Simultaneously, adherens junction tension measured with an E-cadherin probe was unaltered. The stability of JAM-A and ZO-2 binding was assessed by a collaborative in silico study. The absence of ZO-2 also impacted the cell response to the substrate, as monolayers plated in 20 kPa hydrogels developed holes not seen in parental cultures and displayed a retarded elongation and formation of cell aggregates. The absence of ZO-2 was sufficient to induce YAP and Snail nuclear accumulation in cells cultured over glass, but when ZO-2 KD cells were plated in nanostructured ridge arrays, they displayed an increased abundance of nuclear Snail and conspicuous internalization of claudin-4. These results indicate that the absence of ZO-2 also impairs the response of cells to substrate stiffness and exacerbates transformation triggered by substrate topography.
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Actinas , Junções Íntimas , Actinas/metabolismo , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Fosfoproteínas/metabolismoRESUMO
Nowadays, the use of super-resolution microscopy (SRM) is increasing globally due to its potential application in several fields of life sciences. However, a detailed and comprehensive guide is necessary for understanding a single-frame image's resolution limit. This study was performed to provide information about the structural organisation of isolated cellulose fibres from garlic and agave wastes through fluorophore-based techniques and image analysis algorithms. Confocal microscopy provided overall information on the cellulose fibres' microstructure, while techniques such as total internal reflection fluorescence microscopy facilitated the study of the plant fibres' surface structures at a sub-micrometric scale. Furthermore, SIM and single-molecule localisation microscopy (SMLM) using the PALM reconstruction wizard can resolve the network of cellulose fibres at the nanometric level. In contrast, the mean shift super-resolution (MSSR) algorithm successfully determined nanometric structures from confocal microscopy images. Atomic force microscopy was used as a microscopy technique for measuring the size of the fibres. Similar fibre sizes to those evaluated with SIM and SMLM were found using the MSSR algorithm and AFM. However, the MSSR algorithm must be cautiously applied because the selection of thresholding parameters still depends on human visual perception. Therefore, this contribution provides a comparative study of SRM techniques and MSSR algorithm using cellulose fibres as reference material to evaluate the performance of a mathematical algorithm for image processing of bioimages at a nanometric scale. In addition, this work could act as a simple guide for improving the lateral resolution of single-frame fluorescence bioimages when SRM facilities are unavailable.
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Triatoma dimidiata is a species complex, and its members are responsible for the transmission of Trypanosoma cruzi, the causative agent of Chagas disease. We present the assembly and annotation of the mitogenome of the Triatoma dimidiata (Latreille, 1811) and Triatoma huehuetenanguensis Lima-Cordón & Justi, 2019. The mitochondrial genomes were successfully sequenced using the Illumina Nextseq 500 platform, 2×75 cycles, and 5 million reads per sample. Contigs were assembled and annotated using the reference genomes of T. dimidiata and T. huehuetenanguensis available in Genbank (NC_002609 and NC_050325.1, respectively). The mitogenomes of T. dimidiata have lengths of 17,008 bp, while those of T. huehuetenanguensis are 15,910 bp and 15,909 bp. The genome comprises 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a control region. The mitogenomes will be valuable to scholars and students focused on integrative taxonomy, phylogeography, and evolutionary studies of the Triatoma dimidiata complex and the transmission of Chagas diseases.