Machine Learning-Assisted Optimization of Drug Combinations in Zeolite-Based Delivery Systems for Melanoma Therapy.

Two independent artificial neural network (ANN) models were used to determine the optimal drug combination of zeolite-based delivery systems (ZDS) for cancer therapy. The systems were based on the NaY zeolite using silver (Ag+) and 5-fluorouracil (5-FU) as antimicrobial and antineoplastic agents. Different ZDS samples were prepared, and their characterization indicates the successful incorporation of both pharmacologically active species without any relevant changes to the zeolite structure. Silver acts as a counterion of the negative framework, and 5-FU retains its molecular integrity. The data from the A375 cell viability assays, involving ZDS samples (solid phase), 5-FU, and Ag+ aqueous solutions (liquid phase), were used to train two independent machine learning (ML) models. Both models exhibited a high level of accuracy in predicting the experimental cell viability results, allowing the development of a novel protocol for virtual cell viability assays. The findings suggest that the incorporation of both Ag and 5-FU into the zeolite structure significantly potentiates their anticancer activity when compared to that of the liquid phase. Additionally, two optimal AgY/5-FU@Y ratios were proposed to achieve the best cell viability outcomes. The ZDS also exhibited significant efficacy against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus); the predicted combination ratio is also effective against S. aureus, underscoring the potential of this approach as a therapeutic option for cancer-associated bacterial infections.

Valorization of plant by-products in the biosynthesis of silver nanoparticles with antimicrobial and catalytic properties.

Biosynthesis based on natural compounds has emerged as a sustainable approach for the production of metallic nanoparticles (MNP). The main objective of this study was to biosynthesize stable and multifunctional silver nanoparticles (AgNP) using different plant by-products as reducers and capping agents. Extracts obtained from Eucalyptus globulus, Pinus pinaster, Citrus sinensis, Cedrus atlantica and Camellia sinensis by-products, were evaluated. From all plant by-products tested, aqueous extract of eucalyptus leaves (EL), green tea (GT) and black tea (BT) were selected due to their higher antioxidant phenolic content and were individually employed as reducers and capping agents to biosynthesize AgNP. The green AgNP showed zeta potential values of -31.8 to -36.3 mV, with a wide range of particle sizes (40.6 to 86.4 nm), depending on the plant extract used. Green AgNP exhibited an inhibitory effect against various pathogenic bacteria, including Gram-negative (P. putida, E. coli, Vibrio spp.) and Gram-positive (B. megaterium, S. aureus, S. equisimilis) bacteria with EL-AgNP being the nanostructure with the greatest antimicrobial action. EL-AgNP showed an excellent photodegradation of indigo carmine (IC) dye under direct sunlight, with a removal percentage of up to 100% after 75 min. A complete cost analysis revealed a competitive total cost range of 8.0-9.0 €/g for the biosynthesis of AgNP.

Exploring Optimization of Zeolites as Adsorbents for Rare Earth Elements in Continuous Flow by Machine Learning Techniques.

Unsupervised machine learning (ML) techniques are applied to the characterization of the adsorption of rare earth elements (REEs) by zeolites in continuous flow. The successful application of principal component analysis (PCA) and K-Means algorithms from ML allowed for a wide range assessment of the adsorption results. This global approach permits the evaluation of the different stages of the sorption cycles and their optimization and improvement. The results from ML are also used for the definition of a regression model to estimate other REEs' recoveries based on the known values of the tested REEs. Overall, it was possible to remove more than 70% of all REEs from aqueous solutions during the adsorption assays and to recover over 80% of the REEs entrapped on the zeolites using an optimized desorption cycle.

Optimization of iron-ZIF-8 catalysts for degradation of tartrazine in water by Fenton-like reaction.

Optimization of iron zeolitic imidazole framework-8 (FeZIF-8) nanoparticles, as heterogeneous catalysts, were synthesized and evaluated by the Fenton-like reaction for to degrade tartrazine (Tar) in aqueous environment. To achieve this, ZIF-8 nanoparticles were modified with different iron species (Fe2+ or Fe3O4), and subsequently assessed through the Fenton-like oxidation. The effect of different parameters such as the concentration of hydrogen peroxide, the mass of catalyst and the contact time of reaction on the degradation of Tar by Fenton-like oxidation was studied by using the Box-Behnken design (BBD). The BBD model indicated that the optimum catalytic conditions for Fenton-like reaction with an initial pollutant concentration of 30 ppm at pH 3.0 were T = 40 °C and 12 mM of H2O2, 2 g/L of catalyst and 4 h of reaction. The maximum Tar conversion value achieved with the best catalyst, Fe1ZIF-8, was 66.5% with high mineralization (in terms of decrease of total organic carbon - TOC), 44.2%. To assess phytotoxicity, the germination success of corn kernels was used as an indicator in the laboratory. The results show that the catalytic oxidation by Fenton-like reaction using heterogeneous iron ZIF-8 catalysts is a viable alternative for treating contaminated effluents with organic pollutants and highlighted the importance of the validation of the optimized experimental conditions by mathematical models.

Ocular Surface Changes in Primary Open Angle Glaucoma Patients Treated With Topical Antihypertensive Drugs.

PRCIS: In this study, patients with glaucoma undergoing topical antihypertensive (TAH) drugs had changes in the ocular surface and more dry eye symptoms than controls. Clinicians should recognize the influence of TAH drops on exacerbating ocular surface disease. PURPOSE: The purpose of this study was to evaluate the ocular surface of eyes with glaucoma treated with TAH drugs. METHODS: Cross-sectional study that included eyes undergoing TAH drugs due to primary open angle glaucoma and controls. The parameters evaluated were: the basal tear flow (basic secretion test); the tear film osmolarity (TearLab); and the noninvasive break-up time, blink score, lipid layer thickness, tear meniscus height, and loss area of the meibomian glands, measured with the IDRA Ocular Surface Analyser. Presence of symptoms [Ocular Surface Disease Index (OSDI)], dry eye disease (DED, TFOS DEWS II criteria), and corneal fluorescein staining were assessed. RESULTS: We included 154 eyes (154 patients), 77 undergoing TAH drugs for glaucoma (group 1) and 77 of controls (group 2). The tear film osmolarity ( P =0.003) and the loss area of the meibomian glands ( P =0.004) were higher in group 1. The noninvasive break-up time ( P =0.005), lipid layer thickness ( P =0.006), and tear meniscus height ( P =0.001) were lower in group 1. The global OSDI score ( P <0.001), the proportion of eyes with severe disease ( P =0.002), according to the OSDI, and with DED ( P <0.001), according to the TFOS DEWS II criteria, were higher in group 1. The proportion of patients with corneal fluorescein staining was higher in group 1 ( P <0.001). There were no significant differences in eyes taking TAH drugs with and without preservatives ( P >0.127). CONCLUSIONS: DED, in patients with glaucoma, is a multifactorial disease, with a strong contribution from TAH drugs. These eyes had changes in almost every measured parameter, translating into the presence of more dry eye symptoms and corneal damage when compared with controls.

Essential Oils Encapsulated in Zeolite Structures as Delivery Systems (EODS): An Overview.

Essential oils (EO) obtained from plants have proven industrial applications in the manufacturing of perfumes and cosmetics, in the production and flavoring of foods and beverages, as therapeutic agents in aromatherapy, and as the active principles or excipients of medicines and pharmaceutics due to their olfactory, physical-chemical, and biological characteristics. On behalf of the new paradigm of a more natural and sustainable lifestyle, EO are rather appealing due to their physical, chemical, and physiological actions in human beings. However, EO are unstable and susceptible to degradation or loss. To tackle this aspect, the encapsulation of EO in microporous structures as zeolites is an attractive solution, since these host materials are cheap and non-toxic to biological environments. This overview provides basic information regarding essential oils, including their recognized benefits and functional properties. Current progress regarding EO encapsulation in zeolite structures is also discussed, highlighting some representative examples of essential oil delivery systems (EODS) based on zeolites for healthcare applications or aromatherapy.

Real-World Characterization of the Portuguese Population Living with HIV who Initiated Raltegravir Based-Regimens: The REALITY Study.

INTRODUCTION: Although raltegravir has been available since 2007, data are lacking on the Portuguese population living with HIV who initiated this antiretroviral therapy. Hence, this study aimed to characterize the patients who initiated raltegravir-based regimens between January 2015 and December 2017, on sociodemographics, clinical features, and treatment satisfaction. MATERIAL AND METHODS: Observational, retrospective, multicentre study conducted at 11 reference sites. Sociodemographic and clinical data were collected retrospectively from hospital medical records. For participants continuing raltegravir at study inclusion, the HIV Treatment Satisfaction Questionnaire was administered to assess satisfaction with raltegravir-based therapy. Descriptive statistics were performed. Treatment-naïve and treatment-experienced subgroups were compared for demographic and clinical variables. RESULTS: A total of 302 patients were included; mostly men (69.5%) with a mean age of 49 years old. Approximately half of the patients had at least one non-AIDS-related comorbidity at baseline (53.3%), such as hypercholesterolemia, arterial hypertension, diabetes mellitus, and depression. Moreover, 52.3% were treatment-experienced patients with up to two treatments prior to raltegravir. Across the study time points, there was a reduction in the viral load and improvement in CD4 counts in both the treatment-naïve and treatment-experienced subgroups. Continuing users of raltegravir reported high treatment satisfaction (55.4 ± 7.2 points). CONCLUSION: Raltegravir-based regimens seem like a valid therapeutic option in heterogeneous populations of HIV-infected patients, in patients with previous ART experience and as part of first-line therapeutic options alongside with the latest generation of drugs from its class.

Introdução: Apesar de o raltegravir estar disponível desde 2007, os dados na população portuguesa com VIH que iniciou esta terapêutica antirretroviral são escassos. Deste modo, este estudo teve por objetivo caracterizar os doentes que iniciaram um regime terapêutico baseado em raltegravir entre janeiro de 2015 e dezembro de 2017, relativamente a dados sociodemográficos, características clínicas e satisfação com o tratamento. Material e Métodos: Estudo observacional, retrospetivo, multicêntrico conduzido em 11 centros de referência. Os dados sociodemográficos e clínicos foram recolhidos retrospetivamente nos processos clínicos. Os participantes que continuaram o regime com raltegravir após a inclusão no estudo preencheram o HIV Treatment Satisfaction Questionnaire para avaliar a satisfação com a terapêutica. Foram efetuadas análises de estatística descritiva e comparações para as variáveis sociodemográficas e clínicas nos subgrupos de doentes naïve de tratamento e de doentes com experiência terapêutica. Resultados: Foram incluídos 302 doentes, maioritariamente do sexo masculino (69,5%) com idade média de 49 anos. Aproximadamente metade dos doentes tinha pelo menos uma comorbilidade não relacionada com SIDA no início do estudo (53,3%), tais como hipercolesterolemia, hipertensão arterial, diabetes mellitus ou depressão. Adicionalmente, 52,3% eram doentes com experiência terapêutica com até dois tratamentos anteriores ao raltegravir. Ao longo do estudo verificou-se uma redução na carga viral e uma melhoria nas contagens de CD4 em ambos os subgrupos de doentes (doentes naïve de tratamento e doentes com experiência terapêutica). Os doentes com uso continuado de raltegravir reportaram uma elevada satisfação com o tratamento (55,4 ± 7,2 pontos). Conclusão: Os regimes terapêuticos baseados em raltegravir parecem ser uma opção terapêutica válida em populações heterogéneas de doentes infetados com VIH, em doentes com experiência em ART e como tratamento de primeira linha, em paralelo com outras terapêuticas de última geração.

Surface functionalization of zeolite-based drug delivery systems enhances their antitumoral activity in vivo.

Zeolites have attractive features making them suitable carriers for drug delivery systems (DDS). As such, we loaded the anticancer drug 5-fluorouracil (5-FU), into two different zeolite structures, faujasite (NaY) and Linde Type L (LTL), to obtain different DDS. The prepared DDS were tested in vitro using breast cancer, colorectal carcinoma, and melanoma cell lines and in vivo using the chick embryo chorioallantoic membrane model (CAM). Both assays showed the best results for the Hs578T breast cancer cells, with a higher potentiation for 5-FU encapsulated in the zeolite LTL. To unveil the endocytic mechanisms involved in the internalization of the zeolite nanoparticles, endocytosis was inhibited pharmacologically in breast cancer and epithelial mammary human cells. The results suggest that a caveolin-mediated process was responsible for the internalized zeolite nanoparticles. Aiming to boost the DDS efficacy, the disc-shaped zeolite LTL outer surface was functionalized using amino (NH2) or carboxylic acid (COOH) groups and coated with poly-l-lysine (PLL). Positively functionalized surface LTL nanoparticles revealed to be non-toxic to human cells and, importantly, their internalization was faster and led to a higher tumor reduction in vivo. Overall, our results provide further insights into the mechanisms of interaction between zeolite-based DDS and cancer cells, and pave the way for future studies aiming to improve DDS anticancer activity.

Left Lung and Pulmonary Artery Hypoplasia: A Rare Case of Hemoptysis.

Pulmonary hypoplasia or agenesis is a rare congenital disorder that results in lung underdevelopment. This disease is usually found in children but rarely encountered in adults. We describe the case of an 84-year-old woman diagnosed with a unilateral pulmonary hypoplasia presenting simultaneously with left pulmonary artery hypoplasia. Due to this condition, the patient had a lifelong history of pulmonary infections that resulted in several bronchiectases in the affected lung. Moreover, the pulmonary artery hypoplasia led to the development of pulmonary hypertension and collateral circulation causing hemoptysis, giving rise to the patient attending the emergency department. Although we were able to medically manage the hemoptysis, it can be fatal and require surgical intervention. Hence, an early diagnosis is essential so that appropriate follow-up and prompt prevention and treatment of complications, such as pulmonary infections, hemoptysis and pulmonary hypertension, are achieved. LEARNING POINTS: Although rare and typically associated with childhood, lung and pulmonary artery hypoplasia can in exceptional cases be present in adult life.The diagnosis of lung and pulmonary artery hypoplasia is challenging in adults as they can easily be mistaken for more common diseases.Symptoms and complications may be life-threatening, including dyspnea, hemoptysis, recurrent pulmonary infections and pulmonary hypertension.An early diagnosis is extremely important because it allows a close follow-up with consequent timely detection and treatment of serious complications, especially pulmonary hypertension.

A rare cause of vertebral osteomyelitis: the first case report of rat-bite fever in Portugal

Abstract Rat-bite fever is a rarely diagnosed illness caused by Streptobacillus moniliformis . Although this disease is distributed worldwide, there have been few cases reported in Europe. Here, we report a case of vertebral osteomyelitis and sternoclavicular septic arthritis caused by S. moniliformis in a Portuguese patient previously bitten by a rat. Laboratory diagnosis was performed using molecular identification. This is the first case report of rat-bite fever in Portugal. The case described here serves as a reminder for physicians to consider this diagnosis in patients who have developed fever syndromes after being in contact with rodents.

Mapping Knowledge Gaps of Mozambique's Terrestrial Mammals.

A valuable strategy to support conservation planning is to assess knowledge gaps regarding primary species occurrence data to identify and select areas for future biodiversity surveys. Currently, increasing accessibility to these data allows a cost-effective method for boosting knowledge about a country's biodiversity. For understudied countries where the lack of resources for conservation is more pronounced to resort to primary biodiversity data can be especially beneficial. Here, using a primary species occurrence dataset, we assessed and mapped Mozambique's knowledge gaps regarding terrestrial mammal species by identifying areas that are geographically distant and environmentally different from well-known sites. By comparing gaps from old and recent primary species occurrence data, we identified: (i) gaps of knowledge over time, (ii) the lesser-known taxa, and (iii) areas with potential for spatiotemporal studies. Our results show that the inventory of Mozambique's mammal fauna is near-complete in less than 5% of the territory, with broad areas of the country poorly sampled or not sampled at all. The knowledge gap areas are mostly associated with two ecoregions. The provinces lacking documentation coincide with areas over-explored for natural resources, and many such sites may never be documented. It is our understanding that by prioritising the survey of the knowledge-gap areas will likely produce new records for the country and, continuing the study of the well-known regions will guarantee their potential use for spatiotemporal studies. The implemented approach to assess the knowledge gaps from primary species occurrence data proved to be a powerful strategy to generate information that is essential to species conservation and management plan. However, we are aware that the impact of digital and openly available data depends mostly on its completeness and accuracy, and thus we encourage action from the scientific community and government authorities to support and promote data mobilisation.

A rare cause of vertebral osteomyelitis: the first case report of rat-bite fever in Portugal.

Rat-bite fever is a rarely diagnosed illness caused by Streptobacillus moniliformis . Although this disease is distributed worldwide, there have been few cases reported in Europe. Here, we report a case of vertebral osteomyelitis and sternoclavicular septic arthritis caused by S. moniliformis in a Portuguese patient previously bitten by a rat. Laboratory diagnosis was performed using molecular identification. This is the first case report of rat-bite fever in Portugal. The case described here serves as a reminder for physicians to consider this diagnosis in patients who have developed fever syndromes after being in contact with rodents.

A rare presentation of Listeria monocytogenes infection: Perianal abscess associated with lumbar spine osteitis.

Listeria monocytogenes is a ubiquitous, rapidly growing, gram-positive bacterium causing infections in humans and animals. It is responsible for a variety of symptoms depending on the infection site and the integrity of the host's immune system. Case reports of skin and soft tissues infections by Listeria are rare. The authors present a case of a 65-year-old diabetic male with recurrent skin abscess diagnosed with a perianal abscess due to Listeria monocytogenes associated with lumbar spine osteitis. At the time of this publication and to our knowledge, this case represents the first Listeria monocytogenes infection involving skin and bone in a diabetic man with recurrent skin abscess.

Non-AIDS-related comorbidities in people living with HIV-1 aged 50 years and older: The AGING POSITIVE study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Actinomycosis, a lurking threat: a report of 11 cases and literature review.

Actinomycosis remains characteristically uncommon, but is still an important cause of morbidity. Its clinical presentation is usually indolent and chronic as slow growing masses that can evolve into fistulae, and for that reason are frequently underdiagnosed. Actinomyces spp is often disregarded clinically and is classified as a colonizing microorganism. In this review of literature, we concomitantly present 11 cases of actinomycosis with different localizations, diagnosed at a tertiary hospital between 2009 and 2016. We outline the findings of at least one factor of immunosuppression in > 90% of the reported cases.

Actinomycosis, a lurking threat: a report of 11 cases and literature review

Abstract Actinomycosis remains characteristically uncommon, but is still an important cause of morbidity. Its clinical presentation is usually indolent and chronic as slow growing masses that can evolve into fistulae, and for that reason are frequently underdiagnosed. Actinomyces spp is often disregarded clinically and is classified as a colonizing microorganism. In this review of literature, we concomitantly present 11 cases of actinomycosis with different localizations, diagnosed at a tertiary hospital between 2009 and 2016. We outline the findings of at least one factor of immunosuppression in > 90% of the reported cases.