Beyond the adverse effects of the systemic route: Exploiting nanocarriers for the topical treatment of skin cancers.

Skin cancer is a heterogeneous disease that can be divided into two main groups, melanoma and nonmelanoma skin cancers. Conventional therapies for skin cancer have numerous systemic side effects and a high recurrence rate. Topical treatment is an alternative approach, but drug permeability remains a challenge. Therefore, nanocarriers appear as important nanotechnology tools that reduces both the side effects and improves clinical outcomes. This is why they are attracting growing interest. In this review, scientific articles on the use of nanocarriers for the topical treatment of skin cancer were collected. Despite the promising results of the presented nanocarriers and considering that some of them are already on the market, there is an urgent need for investment in the development of manufacturing methods, as well as of suitable toxicological and regulatory evaluations, since the conventional methods currently used to develop these nanocarriers-based products are more time-consuming and expensive than conventional products.

Multisensory effects of mask wearing on speech intelligibility and the benefit of multilingualism / Efeitos multissensoriais do uso de máscara na inteligibilidade da fala e o benefício do multilinguismo

ABSTRACT Purpose Due to the pandemic of the Covid-19 disease, it became common to wear masks on some public spaces. By covering mouth and nose, visual-related speech cues are greatly reduced, while the auditory signal is both distorted and attenuated. The present study aimed to analyze the multisensory effects of mask wearing on speech intelligibility and the differences in these effects between participants who spoke 1, 2 and 3 languages. Methods The study consisted of the presentation of sentences from the SPIN test to 40 participants. Participants were asked to report the perceived sentences. There were four conditions: auditory with mask; audiovisual with mask; auditory without mask; audiovisual without mask. Two sessions were conducted, one week apart, each with the same stimuli but with a different signal-to-noise ratio. Results Results demonstrated that the use of the mask decreased speech intelligibility, both due to a decrease in the quality of auditory stimuli and due to the loss of visual information. Signal-to-noise ratio largely affects speech intelligibility and higher ratios are needed in mask-wearing conditions to obtain any degree of intelligibility. Those who speak more than one language are less affected by mask wearing, as are younger listeners. Conclusion Wearing a facial mask reduces speech intelligibility, both due to visual and auditory factors. Older people and people who only speak one language are affected the most.

RESUMO Objetivo Devido à pandemia da doença Covid-19, o uso de máscaras em espaços públicos tornou-se comum. Ao cobrir a boca e o nariz, reduzem-se amplamente as pistas visuais associadas à fala, assim como se distorce e atenua o sinal auditivo. Este estudo teve como objetivo analisar os efeitos multissensoriais do uso da máscara na percepção da fala e a diferença entre participantes falantes de uma, duas ou três línguas. Método Este estudo consistiu na apresentação de frases do SPIN teste a 40 participantes. Os participantes tinham como tarefa reportar as frases percebidas em quatro condições: Auditiva com máscara, audiovisual com máscara, auditiva sem máscara, audiovisual sem máscara. Conduziram-se duas sessões, com uma semana de intervalo, cada uma com os mesmos estímulos mas com diferente relação sinal-ruído. Resultados Os resultados demonstraram que o uso de máscara reduz a inteligibilidade da fala, tanto devido à diminuição da qualidade do estímulo auditivo, como devido à perda de informação visual. A relação sinal-ruído afeta a inteligibilidade e com o uso de máscara são necessárias relações mais altas para obter qualquer identificação correta. Aqueles que falam mais do que uma língua, assim como os mais novos, são menos afetados na percepção de fala com uso de máscara. Conclusão O uso de máscara facial reduz a inteligibilidade da fala, tanto devido a fatores visuais como auditivos. Indivíduos monolíngues, assim como os mais velhos, são os mais afetados nesta tarefa.

Rosacea Topical Treatment and Care: From Traditional to New Drug Delivery Systems.

Rosacea is a multifactorial chronic inflammatory dermatosis characterized by flushing, nontransient erythema, papules and pustules, telangiectasia, and phymatous alterations accompanied by itching, burning, or stinging, the pathophysiology of which is not yet fully understood. Conventional topical treatments usually show limited efficacy due to the physical barrier property of the skin that hinders skin penetration of the active ingredients, thereby hampering proper drug skin delivery and the respective therapeutic or cosmetic effects. New advances regarding the physiopathological understanding of the disease and the underlying mechanisms suggest the potential of new active ingredients as promising therapeutic and cosmetic approaches to this dermatosis. Additionally, the development of new drug delivery systems for skin delivery, particularly the potential of nanoparticles for the topical treatment and care of rosacea, has been described. Emphasis has been placed on their reduced nanometric size, which contributes to a significant improvement in the attainment of targeted skin drug delivery. In addition to the exposition of the known pathophysiology, epidemiology, diagnosis, and preventive measures, this Review covers the topical approaches used in the control of rosacea, including skin care, cosmetics, and topical therapies, as well as the future perspectives on these strategies.

Characterisation of institutionalised Portuguese older adult fallers: is there a place for pharmacist intervention? A preliminary study.

Background: Falls are a major public health issue, given their prevalence and social impact. Older adults living in long-term care facilities (LTCF) are at greater risk of injury resulting from a fall due to multiple factors, such as nutritional, functional/cognitive impairment, postural instability, polypharmacy, and the presence of potentially inappropriate medications (PIMs). Medication management in LTCF is complex and often sub-optimal and might be crucial for falls. Pharmacist intervention is important, since they have a unique knowledge of medication. However, studies mapping the impact of pharmaceutical activities in Portuguese LTC settings are scarce. Objective: This study aims to assess the characteristics of older adult fallers living in LTFCs and examine the relationship between falling and several factors in this population. We also intend to explore the prevalence of PIMs and their relationship with the occurrence of falls. Methods: The study was conducted in two long-term care facilities for elderly people, in the central region of Portugal. We included patients aged 65 and older with no reduced mobility or physical weakness and with the ability to understand spoken and written Portuguese. The following information was assessed: sociodemographic characteristics, comorbidities, polypharmacy, fear of falling, functional, nutritional and cognitive status. PIMs were evaluated according to the Beers criteria (2019). Results: A total of 69 institutionalised older adults, 45 women and 24 men, with a mean age of 83.14 ± 8.87 years were included. The prevalence of falls was 21.74% Out of these, 46.67% (n=7) fell once, 13.33% (n=2) fell twice, and 40% (n=6) fell 3 or more times. Fallers were mainly women, had lower levels of education, were well nourished, had moderate to severe levels of dependence, and displayed moderate cognitive impairment. All adult fallers had a fear of falling. The main comorbidities of this population were related to the cardiovascular system. Polypharmacy was present in every patient, and at least one PIM was identified in 88.41% of the subjects. Fear of falling (FOF) and cognitive impairment (in subjects with 1 to 11 years of education) showed statistically significant associations with the occurrence of falls (p=0.005 and p=0.05, respectively). No significant differences were found between fallers and non-fallers for any other factors. Conclusions: This present study is a preliminary contribution to characterise a group of older adult fallers living in Portuguese LTCFs and demonstrated that fear of falling and cognitive impairment are associated with the occurrence of falls in this population. The high prevalence of polypharmacy and PIMs emphasises the need for tailored interventions featuring the collaboration of a pharmacist to optimise medication management in this population.

Ethosomes as Nanocarriers for the Development of Skin Delivery Formulations.

The use of nanotechnology has been extensively explored for developing efficient drug delivery systems towards topical and transdermal applications. Ethosomes constitute a vesicular nanocarrier containing a relatively high concentration of ethanol (20-45%). Ethanol is a well-known permeation enhancer, which confers ethosomes unique features, including high elasticity and deformability, allowing them to penetrate deeply across the skin and enhance drug permeation and deposition. The improved composition of ethosomes offer, thereby, significant advantages in the delivery of therapeutic agents over particularly the conventional liposomes regarding different pathologies, including acne, psoriasis, alopecia, skin infections, hormonal deficiencies, among others. This review provides a comprehensive overview of the ethosomal system and an assessment of its potential as an efficient nanocarrier towards the skin delivery of active ingredients. Special attention is given to the composition of ethosomes and the mechanism of skin permeation, as well as their potential applications in different pathologies, particularly skin pathologies (acne, psoriasis, atopic dermatitis, skin cancer and skin infections). Some examples of ethosome-based formulations for the management of skin disorders are also highlighted. Besides the need for further studies, particularly in humans, ethosomal-based formulations hold great promise in the skin delivery of active ingredients, which increasingly asserts oneself as a viable alternative to the oral route.

Plant-mediated green synthesis of metal-based nanoparticles for dermopharmaceutical and cosmetic applications.

The skin is the primordial barrier that protects the human body against environmental factors. Due to the arise of dermatological pathologies, the development of efficient delivery systems for topical applications has received increased interest. The highest challenge consists of increasing the penetration of the active ingredients through the skin barrier, alongside to the need of obtaining enough skin retention to achieve therapeutic concentrations. Metals, specially noble metals, have been used for years to treat and prevent health issues, among them dermatological disorders. Nanoparticles have been extensively used for topical applications given their advantages, namely by enhancing solubility of apolar drugs, the possibility of controlled release, the higher stability and the capability to target specific areas and delivery of high concentrations of active ingredients. In order to take advantage of the before mentioned unique properties of nanoparticles and the biological activities of metals, various metal-based nanoparticles (MNPs) have been synthesized in the past few years, such as silver (AgNPs), gold (AuNPs), zinc (ZnNPs), zinc oxide (ZnONPs), copper (CuNPs) and copper oxide (CuONPs) nanoparticles. These MNPs are flexible structures that allow the control of physical characteristics, with enhanced surface properties, which provides a high applicability in dermopharmacy and cosmetics. The conventional methods for synthesizing nanoparticles (physical and chemical approaches) are associated with major drawbacks, being the most concerning the high cost (in resources, energy, time and space) and human/environmental toxicity. Hence, the need to develop an alternative synthesis pathway was imposed, giving rise to the green synthesis methodology. In general, green synthesis consist of using biological sources (plants, bacteria or fungi) to synthesize ecological benign, non-hazard and biocompatible nanoparticles. With the development of green synthesis, starting materials have been used more frequently, among them plants. Plant-mediated green synthesis of nanoparticles is based on the use of plant extracts to synthesize nanoparticles, and their outstanding advantages have paved the way for exciting developments on nanoparticle synthesis to the detriment of complex and toxicity-associated chemical and physical synthesis. MNPs produced by plant-mediated synthesis also demonstrate notorious biological activities, i.e., anticancer, antioxidant, anti-inflammatory, antimicrobial, wound healing and antiaging activities. However, safety assessment of phyto MNPs (phyto-MNPs) holds significant importance due to the lack of toxicological studies and the conception issues that some of the available studies show. In general, current studies suggest the biocompatibility and safety of phyto-MNPs, together with significantly improved and relevant biological activities towards dermopharmaceutical and cosmetic applications. Against this backdrop, there is still a long way to run until the application of phyto-MNPs in the medical, pharmaceutical and cosmetic fields, but studies so far show a very high potential towards their clinical translation for dermopharmaceutical and cosmetics applications. This review focuses on phyto-MNPs synthesized resorting to various plant extracts, including their production, characterization and the biological activities that support their topical application for dermopharmaceutical and cosmetic purposes.

Implication of low HDL-c levels in patients with average LDL-c levels: a focus on oxidized LDL, large HDL subpopulation, and adiponectin.

To evaluate the impact of low levels of high density lipoprotein cholesterol (HDL-c) on patients with LDL-c average levels, focusing on oxidative, lipidic, and inflammatory profiles. Patients with cardiovascular risk factors (n = 169) and control subjects (n = 73) were divided into 2 subgroups, one of normal HDL-c and the other of low HDL-c levels. The following data was analyzed: BP, BMI, waist circumference and serum glucose Total-c, TGs, LDL-c, oxidized LDL, total HDL-c and subpopulations (small, intermediate, and large), paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF- α , adiponectin, VEGF, and iCAM1. In the control subgroup with low HDL-c levels, significantly higher values of BP and TGs and lower values of PON1 activity and adiponectin were found, versus control normal HDL-c subgroup. However, differences in patients' subgroups were clearly more pronounced. Indeed, low HDL-c subgroup presented increased HbA1c, TGs, non-HDL-c, Ox-LDL, hsCRP, VEGF, and small HDL-c and reduced adiponectin and large HDL. In addition, Ox-LDL, large-HDL-c, and adiponectin presented interesting correlations with classical and nonclassical markers, mainly in the normal HDL-c patients' subgroup. In conclusion, despite LDL-c average levels, low HDL-c concentrations seem to be associated with a poor cardiometabolic profile in a population with cardiovascular risk factors, which is better evidenced by traditional and nontraditional CV biomarkers, including Ox-LDL, large HDL-c, and adiponectin.

Markers of increased cardiovascular risk in postmenopausal women: focus on oxidized-LDL and HDL subpopulations.

OBJECTIVE: To evaluate the effect of gender and menopause in cardiovascular risk (CVR) in a healthy population based on both classical and nontraditional markers. METHODS: 56 men and 68 women (48 pre- and 20 postmenopause) were enrolled in the study. The following markers were analyzed: blood pressure (BP), body mass index (BMI), waist circumference (WC), glucose, total cholesterol (total-c), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-c), oxidized-LDL (Ox-LDL), HDL-c and subpopulations, paraoxonase-1 activity, hsCRP, uric acid, tumor necrosis factor alpha (TNF- α ), adiponectin, vascular endothelial growth factor (VEGF), and intercellular adhesion molecular 1 (ICAM1). RESULTS: Relative to the women, men present significantly increased BMI, WC, BP, glucose, total-c, TGs, LDL-c, Ox-LDL, uric acid, and TNF- α and reduced adiponectin and total and large HDL-c. The protective profile of women is lost after menopause with a significantly increased BMI, WC, BP, glucose, LDL-c, Ox-LDL, hsCRP, and VEGF and decreased total and large HDL-c. Significant correlations were found in women population and in postmenopausal women between Ox-LDL and total, large, and small HDL-c and between TNF- α and total, large, and small HDL-c, LDL-c, and Ox-LDL. CONCLUSIONS: Men present higher CVR than women who lost protection after menopause, evidenced by nontraditional markers, including Ox-LDL and HDL subpopulations.

Diabetes abrogates sex differences and aggravates cardiometabolic risk in postmenopausal women.

BACKGROUND: The aim of this study is to evaluate the effect of gender and menopause in cardiometabolic risk in a type 2 diabetes mellitus (T2DM) population, based on classical and non-traditional markers. METHODS: Seventy four volunteers and 110 T2DM patients were enrolled in the study. Anthropometric data, blood pressure, body mass index (BMI), waist circumference (WC) and the following serum markers were analyzed: glucose, Total-c, TGs, LDL-c, Oxidized-LDL, total HDL-c and large and small HDL-c subpopulations, paraoxonase 1 activity, hsCRP, uric acid, TNF-α, adiponectin and VEGF. RESULTS: Non-diabetic women, compared to men, presented lower glycemia, WC, small HDL-c, uric acid, TNF-α and increased large HDL-c. Diabetes abrogates the protective effect of female gender, since diabetic women showed increased BMI, WC, small HDL-c, VEGF, uric acid, TNF-α and hsCRP, as well as reduced adiponectin, when compared with non-diabetic. In diabetic females, but not in males, WC is directly and significantly associated with TNF-α, VEGF, hsCRP and uric acid; TNF-α is directly associated with VEGF and hsCRP, and inversely with adiponectin. Postmenopausal females presented a worsen cardiometabolic profile, viewed by the increased WC, small HDL-c, VEGF, uric acid, TNF-α and hsCRP. In this population, WC is directly and significantly associated with TNF-α, VEGF, hsCRP; TNF-α is directly associated with VEGF; and uric acid is inversely associated with large HDL-c and hsCRP with adiponectin, also inversely. CONCLUSIONS: Diabetes abrogates the protective effect of gender on non-diabetic women, and postmenopausal diabetic females presented worsen cardiometabolic risk, including a more atherogenic lipid sketch and a pro-inflammatory and pro-angiogenic profile. The classical cardiovascular risk factors (CVRFs) fail to completely explain these differences, which are better clarified using "non-traditional" factors, such as HDL-c subpopulations, rather than total HDL-c content, and markers of inflammation and angiogenesis, namely TNF-α, hsCRP, uric acid and VEGF. Multi-therapeutic intervention, directed to obesity, atherogenic lipid particles and inflammatory mediators is advisory in order to efficiently prevent the serious diabetic cardiovascular complications.

New markers of early cardiovascular risk in multiple sclerosis patients: oxidized-LDL correlates with clinical staging.

OBJECTIVES: This study aimed to characterize a population of multiple sclerosis (MS) patients in terms of traditional and new cardiovascular risk factors and assess their putative correlation with clinical disease activity (evaluated by the Expanded Disability Status Scale [EDSS]). METHODS: Thirty relapsing MS patients and 66 subjects, matched by age and sex, were enrolled in this cross-sectional study. For each subject, anthropometric data were collected and classical biochemical (including lipid profile, glucose and C reactive protein [CRP] levels) and novel markers (paraoxonase 1 [PON1] enzyme activity and contents of high-density lipoprotein [HDL] cholesterol, oxidized low-density lipoprotein [Ox-LDL], tumor necrosis factor [TNF]-alfa, vascular endothelial growth factor [VEGF] and adiponectin) were studied. RESULTS: In patients group, 23 women and 7 men were included, aged 35.00 (28.25-40.25) years and scoring a median of 2.00 (1.50-3.13) in EDSS. Comparing with controls, the most relevant differences encountered were: increased serum triglycerides (P< 0.001), Ox-LDL (P< 0.001) as well as Ox-LDL/LDL ratio and reduced small HDL (P=0.040), accompanied by a trend to increased VEGF concentration. LDL content, especially Ox-LDL, showed positive and significant correlation with EDSS (r=0.458; P=0.011) and VEGF (r=0.453; P=0.014). CONCLUSIONS: MS patients presented a profile of early CV risk, being Ox-LDL contents a putative good marker and having correlation with the clinical activity of the disease.

Main determinants of PON1 activity in hemodialysis patients.

BACKGROUND/AIMS: Cardiovascular diseases are the major cause of morbidity and mortality in hemodialysis (HD) patients. These patients present reduced paraoxonase 1 (PON1) activity that depends on genetic and non-genetic factors; however, how these factors influence PON1 activity in HD patients is poorly clarified. Our aim was to evaluate the influence of two polymorphisms and non-genetic factors on PON1 activity in HD patients. METHODS: We evaluated 183 HD patients under recombinant human erythropoietin (rhEPO) treatment and 22 healthy individuals. The lipid profile [total cholesterol, triglycerides, HDL-c, LDL-c, apolipoprotein (Apo) A-I, Apo B, lipoprotein(a) and oxidized low-density lipoprotein (Ox-LDL)], inflammatory markers [adiponectin, interleukin-6 (IL-6) and C-reactive protein (CRP)], PON1 activity and PON1 gene polymorphisms (L55M and Q192R) were evaluated. RESULTS: HD patients presented higher levels of IL-6, CRP and Ox-LDL/LDL-c, and lower PON1 activity, total cholesterol, HDL-c, LDL-c, Apo A and Apo B; the most frequent genotype was heterozygosity for L55M polymorphism and homozygosity for the Q allele, the more frequent genotype of Q192R polymorphism. Multiple regression analysis identified heterozygosity and homozygosity for L55M and Q192R polymorphisms, very low-density lipoproteins, LDL-c, Apo A and CRP levels, time on dialysis and rhEPO dose, as the independent variables significantly associated with PON1 activity. The associations with CRP, rhEPO and time on dialysis were negative. CONCLUSION: Our results show that the reduced PON1 activity in HD patients who are not under statin therapy is strongly associated with inflammation, longer time on dialysis and high rhEPO doses, suggesting that the reduction in PON1 activity may worsen the prognosis of these patients.