Keratoconus (KC) is a bilateral progressive corneal ectasia resulting in irregular astigmatism and loss of visual function, in youth and children. Corneal cross‐linking (CXL) is the standard ...treatment to halt the progression of KC. The conventional protocol consists of removal of the corneal epithelium (epi‐off), followed by soaking of riboflavin and then irradiation with UVA light, leading to stiffening of the cornea. However, postoperative ocular adverse events related to epithelial removal, such as infectious keratitis and delayed visual recovery, have been described. Some alternative methodologies have been tested but pain, no control on corneal permeability, and high investment for set‐up acquisition are drawbacks. Accordingly, the treatment of KC is at an extremely exciting stage, and research on delivering riboflavin into the cornea without removing the epithelium is underway.
To address this clinical unmet need, we developed an advanced solution consisting of nanoparticle‐modified commercial soft contact lenses. Safety conditions were determined using ex vivo porcine eyes. The efficacy of our solution on corneal epithelial permeability to riboflavin was tested using in vivo rat eyes. Our nanotechnology‐based solution allows high spatial and temporal precision control of epithelial permeability to riboflavin. We aim to validate this innovative strategy as an epithelium‐on (epi‐on) protocol for the effective treatment of KC, with obvious advantages in terms of safety, patient comfort, and recovery time. Furthermore, our strategy is compatible with current equipment and riboflavin solutions, allowing to capitalize clinicians' expertise and the resources already existing in private clinics and public health services.
This project was financially supported by Foundation for Science and Technology (FCT, Portugal): Exploratory Research Project EXPL/BIA‐BQM/0042/2021, Strategic Projects UIDB/04539/2020, UIDP/04539/2020, and UID/NEU/04539/2019; and by COMPETE‐FEDER (POCI‐01‐0145‐FEDER‐007440).
The sea urchin Paracentrotus lividus (Lamarck, 1816) (Echinodermata: Echinoidea) is an important economic resource in Europe, but intense harvesting has led to the collapse of several natural ...populations. Echinoculture, associated with restocking and stock enhancement practices, is an alternative to this problem. In these procedures, reliable individual identification through tagging is a valuable source of information. However, very few studies address the effect of tagging methods on P. lividus and the tagging of marine invertebrates still presents several challenges: decreased growth, high mortality rates and low tag retention rates. Under laboratory conditions, the present study evaluated the effectiveness of three tagging methods (passive integrated transponders PIT-tags, coded wire tags CWTs and calcein) on wild P. lividus for 60 days in terms of total wet weight, total weight gain (mg ind.−1 day−1), survival and tag retention. The final total wet weight was significantly higher in the untagged (control) group than in the PIT-tagged group. Survival rate was 100% for the PIT-tag, calcein and control groups, and 97% for the CWT group. Tag retention differed significantly according to the tagging method: 100% in the calcein group, 76.7% in the PIT-tag group and 38.0% in the CWT group.
Despite the wide application of quantum dots (QDs) in electronics, pharmacy and nanomedicine, limited data is available on their environmental health risk. To advance our current understanding of the ...environmental impact of these engineered nanomaterials, the aim of this review is to give a detailed insight on the existing information concerning the behaviour, transformation and fate of QDs in the aquatic environment, as well as on its mode of action (MoA), ecotoxicity, trophic transfer and biomagnification at various trophic levels (micro-organisms, aquatic invertebrates and vertebrates). Data show that several types of Cd-based QDs, even at low concentrations (<mgCdL−1), induce different toxic effects compared to their dissolved counterpart, indicating nano-specific ecotoxicity. QD ecotoxicity at different trophic levels is highly dependent on its physico-chemical properties, environmental conditions, concentration and exposure time, as well as, species, while UV irradiation increases its toxicity. The state of the art regarding the MoA of QDs according to taxonomic groups is summarised and illustrated. Accumulation and trophic transfer of QDs was observed in freshwater and seawater species, while limited biomagnification and detoxification processes were detected. Finally, current knowledge gaps are discussed and recommendations for future research identified. Overall, the knowledge available indicates that in order to develop sustainable nanotechnologies there is an urgent need to develop Cd-free QDs and new “core-shell-conjugate” QD structures.
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•State-of-the-art of quantum dots (QDs) ecotoxicity•Mode of action and ecotoxicity of QDs at various tropic levels•Development of standard protocols for QD ecotoxicity tests is required.•Urgent need to develop Cd-free QDs and new “core-shell-conjugate” structures
The LEAN methodology is an integration of methods and tools developed in the 90s in the industrial sector. It aims to reduce waste (things that don't add value to the final product), add worth and ...work towards continuous quality improvement.
LEAN tools to improve the clinical practice of a health center include:5S methodology: helps organize, clean, develop and maintain a productive work environment;'Spaghetti' diagram: displays the movement and distance that a given element has to travel throughout the entire process; andTime and motion studies: measure the various times associated with the process and the associated motion.
The LEAN methodology made it possible to manage space and time efficiently and optimally. There was a substantial reduction in both the time and number of trips for not only the health professionals but also for the patients.
Clinical practice should focus on the permission of continuous quality improvement. The LEAN methodology, through its different tools, generates an increase in productivity and profitability. It promotes teamwork through multidisciplinary teams and the empowerment and training of employees. The implementation of the LEAN methodology improved the practices and strengthened the team spirit based on everyone's participation, because the whole is greater than the sum of the parts.
Em 2021, a editora Planeta Tangerina publicou um novo título, Pardalita, na coleção juvenil Dois Passos e um Salto. Este trabalho pretende analisar aquela obra de ficção juvenil, escrita e ilustrada ...por Joana Estrela, à luz do mito de Hero e Leandro. A partir das Heróides, de Ovídio, e de outras referências existentes na obra, irá refletir-se sobre as formas e dimensões em que o mito se torna presente, se atualiza, salientando-se, nesse sentido, os temas que convoca e desenvolve.
DNA-protein interactions are essential for several molecular and cellular mechanisms, such as transcription, transcriptional regulation, DNA modifications, among others. For many decades scientists ...tried to unravel how DNA links to proteins, forming complex and vital interactions. However, the high number of techniques developed for the study of these interactions made the choice of the appropriate technique a difficult task. This review intends to provide a historical context and compile the methods that describe DNA-protein interactions according to the purpose of each approach, summarise the respective advantages and disadvantages and give some examples of recent uses for each technique. The final aim of this work is to help in deciding which technique to perform according to the objectives and capacities of each research team. Considering the DNA-binding proteins characterisation, filter binding assay and EMSA are easy in vitro methods that rapidly identify nucleic acid-protein binding interactions. To find DNA-binding sites, DNA-footprinting is indeed an easier, faster and reliable approach, however, techniques involving base analogues and base-site selection are more precise. Concerning binding kinetics and affinities, filter binding assay and EMSA are useful and easy methods, although SPR and spectroscopy techniques are more sensitive. Finally, relatively to genome-wide studies, ChIP-seq is the desired method, given the coverage and resolution of the technique. In conclusion, although some experiments are easier and faster than others, when designing a DNA-protein interaction study several concerns should be taken and different techniques may need to be considered, since different methods confer different precisions and accuracies.
Introduction
Pediatric pulmonary embolism (PE) is rare but associated with adverse outcomes. We aimed to characterize PE cases admitted in a tertiary hospital and to evaluate sensitivity of selected ...PE diagnostic prediction tools.
Methods
Retrospective, descriptive study of PE cases admitted from 2008 to 2020 using data collected from hospital records. Patients were grouped according to PE severity and setting (outpatients vs. inpatients). Links and correlation with demographic characteristics, risk factors, clinical presentation, management, and outcomes were analyzed. PE diagnostic prediction tools were applied.
Results
Twenty‐nine PE episodes occurred in 27 patients, 62.9% female, mean age 14.1 years. Most PE were central and split between massive or submassive. One was diagnosed in autopsy. Twenty outpatients, all adolescents, were admitted for classic PE symptoms; in half of them the diagnosis had been previously missed. Risk factors included contraceptives (65%), thrombophilia (35%), obesity (20%) and auto‐immunity (20%). Eight inpatients, diagnosed during cardiorespiratory deterioration (n = 5), or through incidental radiological findings (n = 3), were younger and had immobilization (87.5%), complex chronic diseases (75%), infections (75%) and central venous catheter (62.5%) as risk factors. Retrospectively,
d
‐dimer testing and adult scores performed better than pediatric scores (sensitivity 92.9%–96% vs. 85.7%–92.9%). Both pediatric scores missed a case with a positive family history.
Discussion
Pediatric PE diagnosis is often delayed or missed. Development of pediatric prediction tools from validated adult scores merits being explored. We argue clinical presentation and risk factors may be different in inpatients and outpatients and propose broader reliance on family history.
•A high prevalence of non-AIDS-related comorbidities (NARC) was found in Portuguese HIV-infected patients ≥50 years old.•The most common NARC were metabolic, cardiovascular, and psychological ...conditions.•Lipid-lowering and antihypertensive agents were the most common co-medications.•Age and duration of HIV infection were modestly associated with the number of NARC.
To characterize the profile of non-AIDS-related comorbidities (NARC) in the older HIV-1-infected population and to explore the factors associated with multiple NARC.
This was a multicentre, cross-sectional study including HIV-1-infected patients aged ≥50 years, who were virologically suppressed and had been on a stable antiretroviral therapy (ART) regimen for at least 6 months. A multiple regression model explored the association between demographic and clinical variables and the number of NARC.
Overall, 401 patients were enrolled. The mean age of the patients was 59.3 years and 72.6% were male. The mean duration of HIV-1 infection was 12.0 years and the median exposure to ART was 10.0 years. The mean number of NARC was 2.1, and 34.7% of patients had three or more NARC. Hypercholesterolemia was the most frequent NARC (60.8%), followed by arterial hypertension (39.7%) and chronic depression/anxiety (23.9%). Arterial hypertension and diabetes mellitus were the most frequently treated NARC (95.6% and 92.6% of cases, respectively). The linear regression analysis showed a positive relationship between age and NARC (B=0.032, 95% confidence interval 0.015–0.049; p=0.0003) and between the duration of HIV-1 infection and NARC (B=0.039, 95% confidence interval 0.017–0.059; p=0.0005).
A high prevalence of NARC was found, the most common being metabolic, cardiovascular, and psychological conditions. NARC rates were similar to those reported for the general population, suggesting a larger societal problem beyond HIV infection. A multidisciplinary approach is essential to reduce the burden of complex multi-morbid conditions in the HIV-1-infected population.
High‐dose methylprednisolone plus rituximab (R‐HDMP) is a useful treatment in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) patients unfit for chemo‐immunotherapy and has proven ...its utility on the treatment of CLL/SLL complicated by auto‐immune cytopenias. We performed a retrospective, single‐centre study, of CLL/SLL patients treated with R‐HDMP for 9 years. Thirty‐nine patients were included, median age at time of treatment was 77 years. Most patients had stage Rai III/IV and Binet C disease. Twenty‐eight patients had relapsed/refractory disease at time of treatment with a median of 1 previous line of therapy; 53.8% had prior exposure to fludarabine and 25% to rituximab. Grade 3–4 neutropenia and thrombocytopenia were recorded in 10.2% and 17.9% patients, respectively. While on treatment, 51.3% had documented infectious complications, but no other non‐haematological toxicities grades 3–4 were identified. Overall response rate was 64%. Median overall survival and progression‐free survival were 24 and 13 months, respectively. Twenty four patients relapsed and 16 received another line of treatment after R‐HDMP, with median time to next treatment of 13.5 months. Thirteen out of the 24 patients improved performance status and were subsequently considered fit for chemo‐immunotherapy. R‐HDMP is a valuable option for elderly and frail patients, with low risk of severe myelotoxicity and other severe adverse events. It was shown to work as a bridge to other lines of treatment, including chemo‐immunotherapy.
High dose methylprednisolone plus rituximab (R‐HDMP) is a useful treatment in chronic lymphocytic leukaemia/small lymphocytic lymphoma patients unfit for chemo‐immunotherapy. We present a cohort of patients with median age of 77 years, most with stage Rai III/IV and Binet C disease. Overall response rate was 64% and median overall survival and progression‐free survival were 24 and 13 months, respectively, with an acceptable toxicity profile, highlighting R‐HDMP utility for elderly and frail patients.
Antineoplastic drugs used in chemotherapy were detected in aquatic environment: despite the very low concentrations (ng L−1 to ug L−1), due to their potent mechanism of action they could have adverse ...effects on non-target aquatic organisms particularly under chronic exposure. Cisplatin (CDDP) is one of the most effective anticancer drug currently in use but information on its ecotoxicological effects is very limited. In this study, Mytilus galloprovincialis was used to investigate the toxic effects related to CDDP exposure. Mussels were exposed to cisplatin (100 ng L−1) for 14 days: antioxidant (superoxide dismutase, catalase, total and selenium-dependent glutathione peroxidase) and phase II (glutathione-S-transferase) enzymes activities, oxidative damage (lipid peroxidation), genotoxicity (DNA damage) and neurotoxicity (acetylcholinesterase) was evaluated. Results indicate that CDDP at tested concentration induce changes in the antioxidant capacity, oxidative stress in target organs (digestive gland and gills) as well as DNA damage in mussel hemocytes and neurotoxicity representing a risk for non-target organisms.
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•CDDP effects were assessed in marine mussel Mytilus galloprovincialis.•Exposure to CDDP (worst case scenario) imbalanced the activity of defense enzymes in gills and digestive gland.•Neurotoxicity, oxidative and DNA damage were noticed.•Integrative biomarker response is an useful tool for assessing CDDP affect.
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