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1.
Braz J Biol ; 84: e282840, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38985071

RESUMO

Bisphenol A (BPA) may adversely affect human health by inducing oxidative stress and irreversible damage to cells. Bioactive compounds found in some functional foods, individually or in combination, can attenuate the negative effects of BPA exposure; an example is the multi-supplement containing guarana (Gua), selenium (Se), and L-carnitine (LC) -GSC- which has already demonstrated antioxidant, genoprotective, and immunomodulatory activities. This study aimed to determine the effect of GSC and its constituents on oxidative and genotoxic alterations triggered by BPA exposure in the retinal epithelial cell line. The cells exposed to BPA (0.001, 0.01, 0.1, 1, 3, and 10 µM) to determine the lowest concentration required to induce cyto-genotoxicity. ARPE-19 cells were then concomitantly exposed to the selected BPA concentration, GSC, and its components (Gua, 1.07 mg/mL; Se, 0.178 µg/mL; and LC, 1.43 mg/mL). Flow cytometry, biochemical assays, qRT-PCR, genotoxicity, apoptosis, and cellular proliferation. Based on our results, 10 µM of BPA could induce cyto-genotoxic and oxidative alterations. BPA did not alter the Bcl-2/BAX expression ratio but induced Casp3 and Casp8 overexpression, suggesting that apoptosis was induced mainly via the extrinsic pathway. GSC partially reversed the alterations triggered by BPA in ARPE-19 cells. However, Se had unexpected negative effects on ARPE-19 cells. The multi-supplement GSC may attenuate changes in oxidative and genotoxic markers related to exposure of ARPE-19 cells to BPA. our results revealed that the antioxidant, anti-apoptotic, and genoprotective properties of GSC were not universally shared by its individual, once Se did not exhibit any positive impact.


Assuntos
Apoptose , Compostos Benzidrílicos , Carnitina , Estresse Oxidativo , Fenóis , Epitélio Pigmentado da Retina , Selênio , Fenóis/toxicidade , Compostos Benzidrílicos/toxicidade , Humanos , Selênio/farmacologia , Carnitina/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular , Paullinia/química , Dano ao DNA/efeitos dos fármacos , Antioxidantes/farmacologia , Células Epiteliais/efeitos dos fármacos , Citometria de Fluxo , Suplementos Nutricionais
2.
Transgenic Res ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856866

RESUMO

Plants evolved, over millions of years, complex defense systems against pathogens. Once infected, the interaction between pathogen effector molecules and host receptors triggers plant immune responses, which include apoptosis, systemic immune response, among others. An important protein family responsible for pathogen effector recognition is the nucleotide binding site-leucine repeat rich (NBS-LRR) proteins. The NBS-LRR gene family is the largest disease resistance gene class in plants. These proteins are widely distributed in vascular plants and have a complex multigenic cluster distribution in plant genomes. To counteract the genetic load of such a large gene family on fitness cost, plants evolved a mechanism using post transcriptional gene silencing induced by small RNAs, particularly microRNAs. For the NBS-LRR gene family, the small RNAs involved in this silencing mechanism are mainly the microRNA482/2118 superfamily. This suppression mechanism is relieved upon pathogen infection, thus allowing increased NBS-LRR expression and triggering plant immunity. In this review, we will discuss the biogenesis of microRNAs and secondary RNAs involved in this silencing mechanism, biochemical and structural features of NBS-LRR proteins in response to pathogen effectors and the evolution of microRNA-based silencing mechanism with a focus on the miR482/2118 family. Furthermore, the biotechnological manipulation of microRNA expression, using both transgenic or genome editing approaches to improve cultivated plants will be discussed, with a focus on the miR482/2118 family in soybean.

4.
Braz J Biol ; 84: e279474, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38747862

RESUMO

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


Assuntos
Animais Recém-Nascidos , Bothrops , Venenos de Crotalídeos , Animais , Bothrops/classificação , Bothrops/fisiologia , Feminino , Masculino , Fatores Sexuais
5.
Braz J Med Biol Res ; 57: e13250, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38808886

RESUMO

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.


Assuntos
Apoptose , Neoplasias da Mama , Movimento Celular , Proliferação de Células , DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Oxirredução , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Feminino , Movimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Fenótipo , Células MCF-7 , Antineoplásicos/farmacologia
6.
J Dairy Sci ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608938

RESUMO

Our objective was to estimate the requirements of metabolizable energy (ME) and net energy for the maintenance (NEm) of lactating and dry cows, the efficiency of ME utilization for milk production (kl) and tissue gain (kg), and the use of body energy mobilization for milk production (kt) throughout the lactation of primiparous crossbred Holstein × Gyr cows, using open-circuit respiration chambers. Twenty-nine primiparous Holstein × Gyr crossbred cows with an initial BW averaging 563 ± 40.1 kg and 2.5 ± 0.09 years old were used throughout lactation and dry periods. The cows were kept non-pregnant throughout the study to eliminate possible confounding factors. Apparent digestibility assays, followed by calorimeter measurements, were performed 6 times throughout the lactation period. In the dry-off period, the cows were also evaluated but fed with restricted intake (DMI = 1.1% BW/d) to achieve heat production close to maintenance. After 21 d of diet adaptation, an apparent digestibility assay followed by calorimeter measurements was performed. Parameter estimates for lactation period were obtained by mixed models including lactation stage as repeated measures. For restricted feeding at dry-off and fasting period assays, the requirements were estimated by exponential regression. For whole lactation, the values of MEm and NEm were 0.588 and 0.395 MJ/BW0.75, respectively. The efficiencies klkgkt were 0.672, 0.771, and 0.814, respectively. However, MEm and NEm were higher in early and mid-lactation than late, while kl was higher in early than other lactation stages. Dry and non-pregnant cows had MEm of 0.434 MJ/BW0.75 and NEm of 0.351 MJ/BW0.75 for maintenance level, and MEm of 0.396 MJ/BW0.75 and NEm of 0.345 MJ/BW0.75 for fasting metabolism level and efficiency of ME utilization for maintenance was 0.80. Our findings confirmed that F1 crossbred Holstein × Gyr dairy cows have differences in energy requirement and efficiency throughout the lactation stages, suggesting the use of different values in each stage. The estimated values of energy requirement for maintenance and efficiencies for primiparous lactating crossbred Holstein × Gyr were similar to those reported in the literature in specific studies and requirements systems.

7.
Neurobiol Dis ; 196: 106518, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38679112

RESUMO

Resting tremor is the most common presenting motor symptom in Parkinson's disease (PD). The supplementary motor area (SMA) is a main target of the basal-ganglia-thalamo-cortical circuit and has direct, facilitatory connections with the primary motor cortex (M1), which is important for the execution of voluntary movement. Dopamine potentially modulates SMA and M1 activity, and both regions have been implicated in resting tremor. This study investigated SMA-M1 connectivity in individuals with PD ON and OFF dopamine medication, and whether SMA-M1 connectivity is implicated in resting tremor. Dual-site transcranial magnetic stimulation was used to measure SMA-M1 connectivity in PD participants ON and OFF levodopa. Resting tremor was measured using electromyography and accelerometry. Stimulating SMA inhibited M1 excitability OFF levodopa, and facilitated M1 excitability ON levodopa. ON medication, SMA-M1 facilitation was significantly associated with smaller tremor than SMA-M1 inhibition. The current findings contribute to our understanding of the neural networks involved in PD which are altered by levodopa medication and provide a neurophysiological basis for the development of interventions to treat resting tremor.


Assuntos
Antiparkinsonianos , Eletromiografia , Levodopa , Córtex Motor , Doença de Parkinson , Estimulação Magnética Transcraniana , Tremor , Humanos , Levodopa/uso terapêutico , Levodopa/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Masculino , Córtex Motor/efeitos dos fármacos , Córtex Motor/fisiopatologia , Feminino , Tremor/fisiopatologia , Tremor/tratamento farmacológico , Idoso , Pessoa de Meia-Idade , Estimulação Magnética Transcraniana/métodos , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/farmacologia , Vias Neurais/fisiopatologia , Vias Neurais/efeitos dos fármacos , Potencial Evocado Motor/efeitos dos fármacos , Potencial Evocado Motor/fisiologia
8.
Neuroimage Clin ; 42: 103590, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38513535

RESUMO

BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.


Assuntos
COVID-19 , Angiografia por Tomografia Computadorizada , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores , Angiografia por Tomografia Computadorizada/métodos , COVID-19/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Prognóstico , Estudos Prospectivos , SARS-CoV-2 , Acidente Vascular Cerebral/diagnóstico por imagem
9.
Clin Radiol ; 79(5): 323-329, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38429136

RESUMO

Interstitial lung diseases (ILDs) are a heterogeneous group of conditions characterised by non-infective inflammation and scarring of the lung parenchyma. They are not infrequently encountered by the general radiologist in both acute and outpatient reporting settings who may even be the first to make the diagnosis. In the acute setting, patients with ILD can present with respiratory deterioration due to a number of causes and in addition to the common causes of dyspnoea, an acute exacerbation of ILD needs to be considered. An exacerbation can be initiated by common triggers such as infection, pulmonary embolism (PE), and heart failure, and it can also be initiated by an insult to the lung or occur due to an unknown cause. Particular care needs to be taken when interpreting computed tomography (CT) examinations in these patients as the findings of an acute exacerbation are non-specific and patient and technical factors can cause spurious appearances including dependent changes, breathing artefact and contrast medium opacification. In the non-acute setting, patients with ILD are at increased risk of lung cancer and pulmonary hypertension (PH), with lung cancer being a particularly important consideration as treatments carry the risk of triggering an acute exacerbation or deterioration in lung function. Overall, this review aims to provide an overview for the general radiologist of additional factors to consider when interpreting scans in patients with ILD and how the presence of ILD impacts the differential diagnoses and complications that can occur in these patients in both acute and non-acute settings.


Assuntos
Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/complicações , Pulmão/diagnóstico por imagem , Prognóstico , Dispneia , Progressão da Doença
10.
Braz. j. med. biol. res ; 57: e13250, fev.2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1557307

RESUMO

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.

12.
Proteins ; 92(2): 219-235, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37814578

RESUMO

Interleukin-4 (IL-4) is a hematopoietic cytokine composed by a four-helix bundle stabilized by an antiparallel beta-sheet and three disulfide bonds: Cys3-Cys127, Cys24-Cys65, and Cys46-Cys99. IL-4 is involved in several immune responses associated to infection, allergy, autoimmunity, and cancer. Besides its physiological relevance, IL-4 is often used as a "model" for protein design and engineering. Hence, to understand the role of each disulfide in the structure and dynamics of IL-4, we carried out several spectroscopic analyses (circular dichroism [CD], fluorescence, nuclear magnetic resonance [NMR]), and molecular dynamics (MD) simulations on wild-type IL-4 and four IL-4 disulfide mutants. All disulfide mutants showed loss of structure, altered interhelical angles, and looser core packings, showing that all disulfides are relevant for maintaining the overall fold and stability of the four-helix bundle motif, even at very low pH. In the absence of the disulfide connecting both protein termini Cys3-Cys127, C3T-IL4 showed a less packed protein core, loss of secondary structure (~9%) and fast motions on the sub-nanosecond time scale (lower S2 order parameters and larger τc correlation time), especially at the two protein termini, loops, beginning of helix A and end of helix D. In the absence of Cys24-Cys65, C24T-IL4 presented shorter alpha-helices (14% loss in helical content), altered interhelical angles, less propensity to form the small anti-parallel beta-sheet and increased dynamics. Simultaneously deprived of two disulfides (Cys3-Cys127 and Cys24-Cys65), IL-4 formed a partially folded "molten globule" with high 8-anilino-1-naphtalenesulphonic acid-binding affinity and considerable loss of secondary structure (~50%decrease), as shown by the far UV-CD, NMR, and MD data.


Assuntos
Dissulfetos , Interleucina-4 , Conformação Proteica , Interleucina-4/química , Dissulfetos/química , Estrutura Secundária de Proteína , Espectroscopia de Ressonância Magnética , Dicroísmo Circular
13.
Cryo Letters ; 44(4): 208-218, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37883138

RESUMO

BACKGROUND: The use of sulfated polysaccharides (PS) in seminal cooling is known to improve seminal quality. OBJECTIVE: To evaluate the effect of different concentrations of PS, extracted from the macroalgae Gracilaria domigensis as a supplement to the seminal cooling medium of the reophilic fish Prochilodus brevis (common curimatã). MATERIALS AND METHODS: Five semen pools were diluted in ACP-104 (treatment T1), in BTS® (T2) and in BTS® with different concentrations of PS (0.5 [T3]; 1.0 [T4] and 1.5 [T5]). The samples were cooled for different times (0, 6, 24, 48, 72, 96 and 120 h) and after each hour they were analyzed for: morphology, membrane integrity, DNA integrity and sperm kinetics. RESULTS: There were no significant differences between the treatments containing different concentrations of sulfated polysaccharides. Regarding the different cooling times, it was possible to observe that after hour 96, there was a reduction in the parameters of sperm kinetics. For DNA integrity there was no significant difference in relation to the treatments nor in relation to the hours. For membrane integrity, a reduction was noted as of hour 96, but there was no influence of polysaccharides. For the sperm morphology, there was no statistical difference between the hours, however the BTS was better than the ACP-104. CONCLUSION: It is concluded that the use of polysaccharides in seminal cooling has no negative effect on sperm parameters and proves that seminal cooling keeps the material viable for up to 72 hours. Doi: 10.54680/fr23410110512.


Assuntos
Caraciformes , Preservação do Sêmen , Animais , Masculino , Sêmen , Motilidade dos Espermatozoides , Sulfatos , Criopreservação , Espermatozoides , DNA , Suplementos Nutricionais
14.
Clin Radiol ; 78(12): 885-894, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37709611

RESUMO

Anterior mediastinal masses can be difficult to characterise on computed tomography (CT) due to the wide spectrum of normal appearances of thymic tissue as well as the challenge of differentiating between benign and malignant pathologies. Additionally, attenuation of cystic mediastinal lesions can be misinterpreted on CT due to varying attenuation values. Anecdotally, non-vascular magnetic resonance imaging (MRI) of the thorax is underutilised across radiology departments in the UK, but has been shown to improve diagnostic certainty and reduce unnecessary surgical intervention. T2-weighted MRI is useful in confirming the cystic nature of lesions, whereas chemical shift techniques can be utilised to document the presence of macroscopic and intra-cellular fat and thus help distinguish between benign and malignant pathologies. In this review article, we present a practical approach to using MRI for the characterisation of anterior mediastinal lesions based on our clinical experience in a UK district general hospital.


Assuntos
Neoplasias do Mediastino , Humanos , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/patologia , Imageamento por Ressonância Magnética/métodos , Timo/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Mediastino/diagnóstico por imagem
15.
Clin Radiol ; 78(12): 947-954, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37718182

RESUMO

AIM: To determine the proportion of computed tomography (CT) coronary angiography (CTCA) referrals with coronary artery calcification (CAC) evident on previous non-cardiac CT imaging and how this impacted the diagnostic yield for CTCA, the requirement for additional diagnostic testing, and the associated costs to confirm or refute obstructive coronary artery disease (CAD). MATERIALS AND METHODS: A retrospective review of CTCA examinations was undertaken between 01/05/2018 and 31/05/2020 in which the examinations were cross referenced for previous non-gated thoracic CT at Royal United Hospitals Bath. Major epicardial vessel CAC on baseline CT was re-evaluated by published semi-quantitative methods, giving a per-patient CAC score (mild = 1-3, moderate = 4-6, severe >6). Subsequent incomplete CTCA diagnostic yield, further testing, and cost implications were examined. RESULTS: Of the 2140 CTCA examinations identified, 13% (280/2140) had a preceding non-gated thoracic CT (53% female, age 63 ± 11 years). The incomplete diagnostic rate increased with CAC grade, mild 32%, (RR 12; 95% CI 4-40), moderate 64% (RR 25; 95% CI 8-80), severe 75%, (RR 29; 95% CI 9-94). Additional diagnostic testing occurred in 4% for the mild CAC category, and 14% and 42% for moderate and severe, respectively. When severe CAC was identified on a non-gated thoracic CT a cost saving of £171/patient (dobutamine stress echo [DSE]) and £61/patient (myocardial perfusion scintigraphy [MPS]) was established with a direct to functional testing pathway. CONCLUSIONS: In patients referred for CTCA where severe CAC was identified on a preceding non-gated thoracic CT a direct to functional testing altered management in 42% of cases and was cost-effective.


Assuntos
Doença da Artéria Coronariana , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Angiografia Coronária/métodos , Valor Preditivo dos Testes , Doença da Artéria Coronariana/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Angiografia por Tomografia Computadorizada/métodos
16.
Appl Opt ; 62(18): 4935-4941, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37707271

RESUMO

The half-adder is one of the most useful combinational logic functions for data processing. Many research papers in the literature propose nonlinear all-optical half-adders. Few studies propose linear all-optical devices, and those that do usually employ microstructured 2D photonic crystals. This work presents the numerical acquisition of an all-optical half-adder using a linear three-core fiber device. The device presents high performance and acceptable values of fabrication and modulation tolerance. It can be made using any fiber technology and propagated by pulses of any wavelength. Depending on the type of fiber used, the precision needed to fabricate the device's smallest structures can range from 20 nm to 90 nm. This result is evidence of the possibility of obtaining nonlinear logical processing using only fiber design.

17.
Clin Oncol (R Coll Radiol) ; 35(10): 665-672, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37487914

RESUMO

AIMS: In the pivotal RECOURSE trial, trifluridine/tipiracil improved survival outcomes in refractory metastatic colorectal cancer (mCRC), while demonstrating an acceptable toxicity profile. Routine clinical practice evidence is important to support the ongoing value of recently approved medicines. Our objective was to assess the utilisation patterns and real-world effectiveness of trifluridine/tipiracil in previously treated mCRC patients. MATERIALS AND METHODS: This was a retrospective observational study including consecutive patients who started trifluridine/tipiracil between 1 April 2018 and 30 September 2019 in the medical oncology departments of three major public hospitals in Portugal. The primary outcome measure was overall survival. Associations between overall survival and patient and tumour characteristics were assessed using multivariate Cox regression analyses. RESULTS: In total, 111 patients were included in the study, with a mean age of 64 years. From these, 45.9% received two prior lines of treatment, 47.8% had three or more previous lines of treatment and 83.6% had Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at baseline. The median duration of trifluridine/tipiracil treatment was 3.7 cycles (95% confidence interval 3.4-4.1). Most patients (80.4%) remained on their planned dose throughout the trifluridine/tipiracil treatment period, fulfilling 100% relative dose intensity. The median overall survival in the total study cohort was 7.9 months (95% confidence interval 6.4-9.8) and the median progression-free survival was 3.4 months (95% confidence interval 3.2-3.9). The median overall survival was significantly higher in patients with a normal serum lactate dehydrogenase (LDH) level (median overall survival 11.2 months for [135, 205] IU/l LDH [95% confidence interval 8.2-NR] and 13.6 months for [205, 251] IU/l LDH [95% confidence interval 8.2-NR]) and in better fitted (ECOG = 0-1) patients (median overall survival 8.0 months; 95% confidence interval 6.7-10.0). The median time to worsening performance status was 6.2 months (95% confidence interval 5.0-8.0). Treatment discontinuation due to adverse events was low (3.1%). CONCLUSION: Our study confirms the effectiveness of trifluridine/tipiracil in real-life mCRC patients. Overall survival and progression-free survival outcomes are consistent with the efficacy profile reported in the earlier randomised RECOURSE clinical trial. Like other real-world studies, we found no additional safety concerns in the use of trifluridine/tipiracil.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Pessoa de Meia-Idade , Uracila/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Trifluridina/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Combinação de Medicamentos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
18.
J Plast Reconstr Aesthet Surg ; 84: 32-36, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37320949

RESUMO

BACKGROUND: Non-melanoma skin cancer (NMSC) is the most common cancer type and incidence increases with age. As a consequence, an increasing number of frail patients are being referred for consideration of skin cancer surgery. However, some of these patients may not live long enough to experience benefit from surgery, while being at risk of postoperative complications. OBJECTIVES: To investigate the treatment burden of surgical excision of skin cancers in frail individuals. METHODS: We conducted a single-center retrospective cohort study analyzing outcomes of skin cancer excision in frail versus non-frail patients. RESULTS: Eighty-eight patients were included. The complication rate was higher in frail versus non-frail patients: 12 (27.9%) versus 9 (18.8%), with 5 unplanned postoperative hospital attendances leading to 3 hospital admissions in the frail cohort. Nine patients in the frail group (21%) died within 6 months of their procedure versus no deaths in the non-frail group (p < 0.001 Fisher's Exact test), with no deaths attributed to skin cancer. CONCLUSION: Treatment-related complications and mortality are common in frail patients after surgical excision of skin lesions clinically suspicious for skin cancer. Careful consideration should be given, and patients should be adequately counseled about treatment risks and alternative management options, including active surveillance, in particular, if the lesions are expected to remain asymptomatic.


Assuntos
Idoso Fragilizado , Neoplasias Cutâneas , Humanos , Idoso , Estudos Retrospectivos , Neoplasias Cutâneas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hospitais , Fatores de Risco
19.
Plant Biol (Stuttg) ; 25(5): 740-749, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37158679

RESUMO

Aluminium (Al) is toxic to most plants. Nevertheless, some species accumulate Al without showing toxicity symptoms. Previous studies have evidenced Al in chloroplasts of Al-accumulating species from the Cerrado vegetation in South America. We ask whether Al increases carbon assimilation through enhanced apparent efficiency of Rubisco. Seedlings of the Al-accumulator Qualea grandiflora (Vochysiaceae) were grown in nutrient solution with 0, 740, and 1480 µm Al. Growth parameters, relative leaf water content, Al concentration in organs, gas exchange and apparent carboxylation efficiency (measured from A/Ci curves) were evaluated for 60 days. Plants without Al showed no root growth, necrotic roots, low gas exchange rates, and decreased apparent carboxylation efficiency. Al-treated plants, however, showed new white roots and increased root biomass leading to higher leaf hydration, and apparent carboxylation efficiency was higher in these plants. Increased Al available in the nutrient solution increased Al accumulation in plant organs. Absence of Al compromised root integrity in Q. grandiflora, thus limiting leaf hydration. No positive direct effect of Al on Rubisco was evidenced in Al-treated plants.


Assuntos
Alumínio , Myrtales , Alumínio/toxicidade , Ribulose-Bifosfato Carboxilase , Plantas , Plântula , Folhas de Planta , Raízes de Plantas
20.
J Mech Behav Biomed Mater ; 142: 105812, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37084491

RESUMO

This study set out to develop a thermally compatible glass to be infiltrated into zirconia partially stabilized by yttrium oxide (5Y-PSZ), to characterize it, and to evaluate its structural reliability and mechanical behavior. 5Y-PSZ zirconia discs (N = 90), dimensions 1.5 mm × 15 mm were produced, polished with #600 alumina oxide and #1200 silicon carbide sandpaper in a polisher. Three groups of 5Y-PSZ discs were assigned (n = 30): Zctrl: as sintered zirconia, Zinf-comp: glass-infiltrated zirconia on the occlusal surface, and sintered, and Zinf-tens: glass-infiltrated zirconia on the cementing surface and sintered; for biaxial flexural strength testing (ISO 6872:2015). A gel was synthesized via the sol-gel method and applied to the ceramic surface. Mechanical assay data (MPa) were evaluated via Weibull analysis (α = 5%) and specimens via X-Ray Diffractometry (XRD), Scanning Electron Microscopy (SEM), and fractographic analysis. The Zinf-tens group showed a characteristic strength of 824 MPa and m = 9.9; Zinf-comp 613 MPa and m = 10.2; Zctrl 534 MPa and m = 8; all groups differed statistically (σ0). However, they were similar in structural homogeneity (m). XRD showed 20-50 µm of infiltration, which means dissolution of part of the yttrium and reduction in the size of the cubic grains. In addition, the Zinf-tens group presented a failure origin from inside the material. The developed glass infiltrated into zirconia partially stabilized by yttrium oxide, increasing its characteristic strength and structural homogeneity by reducing surface defects and changing the failure mode.


Assuntos
Resistência à Flexão , Zircônio , Teste de Materiais , Reprodutibilidade dos Testes , Zircônio/química , Ítrio/química , Cerâmica/química , Propriedades de Superfície , Materiais Dentários
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