Search

The COVID-19 pandemic has highlighted a debate about whether marginalized communities suffered the disproportionate brunt of the pandemic's mortality. Empirical studies addressing this question typically suffer from statistical uncertainties and potential biases associated with uneven and incomplete reporting. We use geo-coded micro-level data for the entire population of Sweden to analyze how local neighborhood characteristics affect the likelihood of dying with COVID-19 at individual level, given the individual's overall risk of death. We control for several individual and regional characteristics to compare the results in specific communities to overall death patterns in Sweden during 2020. When accounting for the probability to die of any cause, we find that individuals residing in socioeconomically disadvantaged neighborhoods were not more likely to die with COVID-19 than individuals residing elsewhere. Importantly, we do find that individuals show a generally higher probability of death in these neighborhoods. Nevertheless, ethnicity is an important explanatory factor for COVID-19 deaths for foreign-born individuals, especially from East Africa, who are more likely to pass away regardless of residential neighborhood. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has highlighted a debate about whether marginalized communities suffered the disproportionate brunt of the pandemic's mortality. Empirical studies addressing this question typically suffer from statistical uncertainties and potential biases associated with uneven and incomplete reporting. We use geo-coded micro-level data for the entire population of Sweden to analyze how local neighborhood characteristics affect the likelihood of dying with COVID-19 at individual level, given the individual's overall risk of death. We control for several individual and regional characteristics to compare the results in specific communities to overall death patterns in Sweden during 2020. When accounting for the probability to die of any cause, we find that individuals residing in socioeconomically disadvantaged neighborhoods were not more likely to die with COVID-19 than individuals residing elsewhere. Importantly, we do find that individuals show a generally higher probability of death in these neighborhoods. Nevertheless, ethnicity is an important explanatory factor for COVID-19 deaths for foreign-born individuals, especially from East Africa, who are more likely to pass away regardless of residential neighborhood. [ABSTRACT FROM AUTHOR]

We investigate whether an individual's information milieu―an individual's residential neighborhood and co-workers―affects the decision to get a COVID-19 vaccine. The decision to accept or refuse a vaccine is intensely personal and involves the processing of information about phenomena likely to be unfamiliar to most individuals. One can thus expect an interplay between an individual's level of education and skills and the information processing of others whom with whom she can interact and whose decision she can probe and observe. Using individual-level data for adults in Sweden, we can identify the proportion of an individual's neighborhood and workplace who are unvaccinated as indicators of possible peer effects. We find that individuals with low levels of educational attainment and occupational skills are more likely to be unvaccinated when exposed to other unvaccinated individuals at work and in the residential neighborhood. The peer effects in each of these information milieus further increases the likelihood of not getting vaccinated—with the two acting as information channels that reinforce one another. [ABSTRACT FROM AUTHOR]

Urban adaptation to climate change is a global challenge requiring a broad response that can be informed by how urban societies in the past responded to environmental shocks. Yet, interdisciplinary efforts to leverage insights from the urban past have been stymied by disciplinary silos and entrenched misconceptions regarding the nature and diversity of premodern human settlements and institutions, especially in the case of prehispanic Mesoamerica. Long recognized as a distinct cultural region, prehispanic Mesoamerica was the setting for one of the world's original urbanization episodes despite the impediments to communication and resource extraction due to the lack of beasts of burden and wheeled transport, and the limited and relatively late use of metal implements. Our knowledge of prehispanic urbanism in Mesoamerica has been significantly enhanced over the past two decades due to significant advances in excavating, analyzing, and contextualizing archaeological materials. We now understand that Mesoamerican urbanism was as much a story about resilience and adaptation to environmental change as it was about collapse. Here we call for a dialogue among Mesoamerican urban archaeologists, sustainability scientists, and researchers interested in urban adaptation to climate change through a synthetic perspective on the organizational diversity of urbanism. Such a dialogue, seeking insights into what facilitates and hinders urban adaptation to environmental change, can be animated by shifting the long-held emphasis on failure and collapse to a more empirically grounded account of resilience and the factors that fostered adaptation and sustainability. [ABSTRACT FROM AUTHOR]

Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term sequel to pulmonary embolism (PE) whose incidence varies according to different published studies. We have carried out this study to determine its incidence within 2 years after index pulmonary embolism and to study limitations to an early diagnosis. OSIRIS is a multicentre, longitudinal cohort study. Patients were followed for 3, 6, 12, and 24 months after pulmonary embolism using a structured three-step algorithm. A physician-centered questionnaire at least one positive response in a screening proceeded to the second step, transthoracic echocardiography. The third step consisted of ventilation/perfusion lung scintigraphy and right heart catheterisation. A transthoracic echocardiography was performed in patients without positive response in the screening questionnaire after 2 years. CTEPH diagnosis required haemodynamic confirmation by right heart catheterisation and mismatched perfusion defects on lung scintigraphy. A total of 1191 patients were enrolled in 18 Spanish hospitals. Cumulative CTEPH incidence after 2-years PE was: 2.49 % (95 % CI: 1.68–3.56) and the incidence rate of CTEPH was 1.1 cases per 1000 person-months (95 % CI: 0.725; 1.60). The CTEPH algorithm presented a lack of adherence of 29 %; patient and physician preferences posed barriers to the triage algorithm The screening questionnaire, in patients who completed the follow-up, shows a specificity of 91.3 % (89.0–93.2 %) and negative predictive value of 99.4 % (98.4–99.8 %).. OSIRIS provides practiced clinical based data on the chronic thromboembolic pulmonary hypertension incidence and identified barriers to the implementation of a 3-step triage algorithm for its detection. clinicaltrials.gov identifier: NCT03134898. [Display omitted] • Two-year cumulative incidence of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) after pulmonary embolism (PE) was 2.49% (95% CI: 1.68-3.56) • A structured three-step diagnostic algorithm based on clinical assessment starting with a screening questionnaire showed limited feasibility, but a high negative predictive value • Observed barriers from patients and physicians to the implementation of a screening-based CTEPH diagnostic algorithm may support the planning of future studies and help to address training gaps [ABSTRACT FROM AUTHOR]

A critique of tension problems between ethics and digital media is elaborated. It focuses on the automation of human referents, subjected to digital control through big data algorithms, accentuating historical data as distinctions that modify reality. This ranges from the robbery of leisure time, to exhausting material resistance, mixing the imperative of innovation, efficiency and excellence in a constant torrent of notifications, reminders and interrelationships. This forges anxieties and wears out of an intense longing, causing a sense of constant accomplishment: being a consultant and entrepreneur is the goal of freedom as self-sacrifice. [ABSTRACT FROM AUTHOR]

Ethical risks in digital behaviour. Politics, democracy and citizenship Deliberative democracy deployed from phenomenology, from which it wants to return to things themselves as Martin Heidegger affirms is "to allow to see what is shown, as it is shown by itself, effectively by itself" (Heidegger, 2009, p. 45) we will find worlds where digital behaviour stimulates the ethical risks that affect politics, democracy and citizenship; and its implications in the mediations of citizens according to different understandings of the world of social networks with their contributions and effects. [ABSTRACT FROM AUTHOR]

Objective: Sensitive skin is characterized by self‐reported sensory perceptions in response to stimuli that should not provoke unpleasant sensations. Cosmetic products for sensitive skin are designed to minimize these symptoms. This study aimed to unveil the most used active ingredients for sensitive skin in facial care products from the pharmacy and parapharmacy channel. Methods: A pool of products from the pharmacy and parapharmacy channel whose label included the expressions 'sensitive skin', 'reactive skin' or 'intolerant skin' were analysed. The active ingredients were identified from product compositions and ranked in descending order of occurrence. The scientific evidence regarding the mechanism of action and efficacy of each ingredient was also compiled. Results: Eighty‐eight products from 19 multinational brands were included. Niacinamide leads the top, followed by Avena sativa, allantoin, glycyrrhetinic acid and derivatives and Laminaria ochroleuca. Ingredients that can reduce skin inflammation and act on the skin barrier were used in more than half of the products analysed. The clinical studies regarding the active ingredients used in these products remain sparse and lack methodological quality. Among the top ingredients, niacinamide, panthenol and acetyl dipeptide‐1 cetyl ester were the only ones studied on volunteers having sensitive skin, while acetyl dipeptide‐1 cetyl ester and palmitoyl tripeptide‐8 were designed to act on the molecular targets involved in this condition. Conclusion: This study reveals the most used active ingredients in cosmetic products for sensitive skin, as well as the scientific evidence supporting their efficacy and the mechanisms of action. This insight is meaningful for dermatologists and other health professionals to provide customized advice based on the symptomatology of individuals with sensitive skin, and for the formulation of cosmetic products and design of new active ingredients. [ABSTRACT FROM AUTHOR]

One of the most common tendencies of human settlements is for larger settlements to display higher population densities. Work in urban science and archaeology suggests that this densification pattern reflects an emergent spatial equilibrium where individuals balance movement costs with social interaction benefits, leading to increases in aggregate productivity and social interdependence. The temporary camps created by hunters and gatherers exhibit a tendency to become less dense with their population size. The different manner in which hunter-gatherer groups express their sociality in residential space suggests that they typically lack the social structures and material technologies necessary for humans to live at greater spatial densities in permanent settlements. Here we examine why this difference occurs and consider conditions under which hunter-gatherer groups may transition to sedentism and densification. We investigate the relationship between population and area in hunter-gatherer camps using a data set representing a large cross-cultural sample derived from the ethnographic literature. We present a model based on the interplay between social interactions and scalar stress that describes the observed patterns among mobile hunter-gatherers. We find that the transition to a densification scheme does not necessary involve domestic food production, only surpluses and storable resources. [ABSTRACT FROM AUTHOR]

Ethical risks in digital behaviour. Politics, democracy and citizenship Deliberative democracy deployed from phenomenology, from which it wants to return to things themselves as Martin Heidegger affirms is "to allow to see what is shown, as it is shown by itself, effectively by itself" (Heidegger, 2009, p. 45) we will find worlds where digital behaviour stimulates the ethical risks that affect politics, democracy and citizenship; and its implications in the mediations of citizens according to different understandings of the world of social networks with their contributions and effects. [ABSTRACT FROM AUTHOR]

This document provides insights into lipid-based nanosystems and their potential therapeutic applications. Lipid-based nanosystems, such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), liposomes, and others, have been extensively studied for their ability to improve drug transport and efficacy through various routes of administration. The document highlights 16 research articles published in a special issue on lipid-based nanosystems, covering topics such as breast cancer treatment, anti-tumor efficacy, antidepressant activity, and ocular drug delivery. The most investigated diseases include cancer, brain diseases, ocular diseases, skin diseases, microbial infections, and metabolic diseases. The authors express their gratitude to the contributors and reviewers of the special issue for their valuable contributions. [Extracted from the article]

The skin is the largest organ of the human body and has several functions such as barrier against external agents, the maintenance of temperature and homeostatic functions. Skin ageing is a natural process that can be influenced by environmental factors, intrinsic skin factors and lifestyle. UV light plays an important role in skin ageing and can cause spots, requiring the use of depigmenting agents. Nowadays, there is a great demand for ingredients that prevent skin ageing, with natural agents occupying a promising position. Among the natural agents, polyphenols, such as resveratrol and piceatannol, found in grapes, passion fruits and other fruits, have a huge relevance. Great benefits of piceatannol have been reported, so thus, this work focuses specifically on a review of the literature regarding the application of this polyphenol in skin care products. This polyphenol can be used in a wound‐healing, or as anti‐ageing, antioxidant, anti‐acne and skin whitening, among other effects. [ABSTRACT FROM AUTHOR]

A dominant view in economic anthropology is that farmers must overcome decreasing marginal returns in the process of intensification. However, it is difficult to reconcile this view with the emergence of urban systems, which require substantial increases in labor productivity to support a growing non-farming population. This quandary is starkly posed by the rise of Angkor (Cambodia, 9th–fourteenth centuries CE), one of the most extensive preindustrial cities yet documented through archaeology. Here, we leverage extensive documentation of the Greater Angkor Region to illustrate how the social and spatial organization of agricultural production contributed to its food system. First, we find evidence for supra-household-level organization that generated increasing returns to farming labor. Second, we find spatial patterns which indicate that land-use choices took transportation costs to the urban core into account. These patterns suggest agricultural production at Angkor was organized in ways that are more similar to other forms of urban production than to a smallholder system. [ABSTRACT FROM AUTHOR]

Introduction: Syncope has been shown to be a risk factor of bleeding in patients receiving thrombolytic therapy for acute pulmonary embolism (PE). Whether syncope predicts bleeding in a broader population of patients with PE remains unknown. Methods: We used the RIETE registry data to assess whether initial presentation with syncope could predict bleeding in PE patients receiving anticoagulant therapy, and to explore the association between presence of syncope and timing and site of major bleeding events. Results: Among 45,765 patients with acute PE from March 2001 to January 2021, 6760 (14.8%) had syncope. Patients with syncope were older and more likely to have hypotension, tachycardia, hypoxaemia or elevated troponin levels than those without syncope. They also were more likely to receive thrombolytics. During the first 90 days, 1097 patients (2.4%) suffered major bleeding (gastrointestinal 335, hematoma 271 and intracranial 163) and 3611 died (158 had fatal bleeding). Patients with syncope had a higher rate of major bleeding (odds ratio [OR]: 1.63; 95% CI: 1.41–1.89) and a nonsignificantly higher rate of fatal bleeding (OR: 1.47; 95% CI: 0.99–2.17) than those without syncope. Multivariable analysis confirmed that patients with syncope were at increased risk for major bleeding (adjusted hazard ratio [aHR]: 1.34; 95% CI: 1.15–1.55). On sensitivity analysis, the increased risk for major bleeding was confirmed in patients initially receiving anticoagulant therapy without thrombolytics at 7 days (aHR: 1.47; 95% CI: 1.13–1.91) and 90 days (aHR: 1.33; 95%CI: 1.13–1.56). Discussion: Syncope is a predictor of major bleeding events in patients with PE, even among those receiving anticoagulation monotherapy. [ABSTRACT FROM AUTHOR]

The photoprotective skincare segment is in high demand to meet consumer concerns on UV-induced skin damage, with a recent trend towards sunscreen alternatives with a natural origin. In this study, the use of natural ingredients, either from terrestrial or marine origin, in a panel of 444 sunscreen commercial formulations (2021) was analyzed. Ingredients from terrestrial organisms represent the large majority found in the analyzed sunscreen formulations (48%), whereas marine ingredients are present only in 13% of the analyzed products. A deeper analysis regarding the most prevalent families of ingredients from terrestrial and marine organisms used as top ingredients is also presented, as well as their mechanisms of action. This study provides an up-to-date overview of the sunscreen market regarding the use of natural ingredients, which is of relevance for scientists involved in the development of new sunscreens to identify opportunities for innovation. [ABSTRACT FROM AUTHOR]

Background: The Portuguese Pharmaceutical Society (PPS) implemented a system of Continuous Professional Development (CPD) for pharmacists in 2004. This system has evolved throughout the years, and currently all active pharmacists in Portugal are required to participate in the CPD program. Each CPD cycle takes 5 years. In each cycle, pharmacists must collect 15 CPD points, through participation in educational activities. The PPS accreditation process is managed via an online platform, where education/training providers, as well as pharmacists themselves, can submit educational activities for accreditation. Pharmacists may access their CPD status and assess their development at any point. The objective of this study was to analyze and review the educational activities submitted by providers over a 11-year period (2009-2019).Methods: Data from activities were retrieved from the PPS CPD online platform. All educational activities were labeled according to the area of pharmaceutical professional focus, type of promoter, and activity type.Results: During the study 3685 activities were analyzed. Over the last decade, submitted activities for accreditation increased in 52.6%. A significantly high proportion (98.9%) of these activities has been accredited. Promoters of activities were mostly pharmacies sectoral associations (29.6%), consultancy/training companies (19.6%), the PPS (18.5%), pharmaceutical industry (17.7%) and wholesalers' consortia (9.0%). Academia represented only 2.3% of the total amount of educational activities. The most frequent topics were related to "pharmacology & pharmacotherapy" (9.9%), followed by "counselling" (9.8%) and "management & administration" (7.2%). The most accredited type of activities was face-to-face (68.9%) and e-learning trainings (13.1%).Conclusions: This study shows increasing interest in submitting CPD activities for accreditation between 2009 and 2019, but it also demonstrates that Academia could play a more interventive role in the lifelong learning education of Portuguese pharmacists. [ABSTRACT FROM AUTHOR]

The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain. Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE? This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48 h vs anticoagulation alone. The primary outcome was normal echocardiographic RV size 48 h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48 h and 7 days after randomization with respect to the baseline ratio measured at inclusion. The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P =.08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48 h (P <.001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48 h (P <.01). At 90 days, one major bleeding event and one death (both in the ambient air group) had occurred. In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48 h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial. ClinicalTrials.gov; No.: NCT04003116; URL: www.clinicaltrials.gov [Display omitted] [ABSTRACT FROM AUTHOR]

Reductions in the cost of transporting manufactured goods have been an important element in economic development in the recent past, and previous research suggests that the Roman period in Britain also saw substantial reductions in such costs. The authors investigate how far it is possible to measure changes in transport costs by considering the spatial distributions of pottery from known Roman production locations over time. Their analysis of an extensive database of pottery assemblages is designed to evaluate a series of expectations concerning how reductions in transport costs may have affected such assemblages and their distribution. Results suggest that costs were reduced by a factor of about two, leading to related changes in pottery production, distribution, and consumption over time. The ability to quantify changes in transport costs opens new perspectives for investigating the general determinants of economic development using archaeological data. [ABSTRACT FROM AUTHOR]

The intranasal route has been suggested as a promising alternative to improve the direct transport of molecules to the brain, avoiding the need to cross the blood–brain barrier (BBB). In this area, the use of lipid nanoparticles, namely solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has been highlighted as a promising strategy to improve the treatment of neurodegenerative diseases. In this work, formulations containing SLN and NLC that were loaded with astaxanthin that was obtained from different sources (astaxanthin extract (AE) from the algae Haematococcus pluvialis and pure astaxanthin (PA) from the fungi Blakeslea trispora) were prepared for nose-to-brain administration, and comparative in vitro experiments were performed to evaluate the biocompatibility of the formulations with nasal (RPMI 2650) and neuronal (SH-SY5Y) cells. Afterwards, the antioxidant activity of the formulations was evaluated for its potential neuroprotective effects, using different chemical aggressors. Finally, the cellular uptake of the astaxanthin was evaluated for the formulations that showed the greatest neuroprotection of the neuronal cells against chemical-induced damage. On the production day, all the formulations showed a particle size, a high encapsulation efficiency (EE), the presence of nanoparticles with a typical spherical shape, and a polydispersity index (PDI) and zeta potential (ZP) that are suitable for nose-to-brain administration. After three months of storage at room temperature, no significant changes were observed in the characterization parameters, predicting a good long-term stability. Furthermore, these formulations were shown to be safe with concentrations of up to 100 µg/mL in differentiated SH-SY5Y and RPMI 2650 cells. Regarding neuroprotection studies, the PA-loaded SLN and NLC formulations showed an ability to counteract some mechanisms of neurodegeneration, including oxidative stress. Moreover, when compared with the PA-loaded SLN, the PA-loaded NLC showed greater neuroprotective effects against the cytotoxicity induced by aggressors. In contrast, the AE-loaded SLN and NLC formulations showed no significant neuroprotective effects. Although further studies are needed to confirm these neuroprotective effects, the results of this study suggest that the intranasal administration of PA-loaded NLC may be a promising alternative to improve the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Marine sources contain several bioactive compounds with high therapeutic potential, such as remarkable antioxidant activity that can reduce oxidative stress related to the pathogenesis of neurodegenerative diseases. Indeed, there has been a growing interest in these natural sources, especially those resulting from the processing of marine organisms (i.e., marine bio-waste), to obtain natural antioxidants as an alternative to synthetic antioxidants in a sustainable approach to promote circularity by recovering and creating value from these bio-wastes. However, despite their expected potential to prevent, delay, or treat neurodegenerative diseases, antioxidant compounds may have difficulty reaching the brain due to the need to cross the blood–brain barrier (BBB). In this regard, alternative delivery systems administered by different routes have been proposed, including intranasal administration of lipid nanoparticles, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which have shown promising results. Intranasal administration shows several advantages, including the fact that molecules do not need to cross the BBB to reach the central nervous system (CNS), as they can be transported directly from the nasal cavity to the brain (i.e., nose-to-brain transport). The benefits of using SLN and NLC for intranasal delivery of natural bioactive compounds for the treatment of neurodegenerative diseases have shown relevant outcomes through in vitro and in vivo studies. Noteworthy, for bioactive compounds obtained from marine bio-waste, few studies have been reported, showing the open potential of this research area. This review updates the state of the art of using SLN and NLC to transport bioactive compounds from different sources, in particular, those obtained from marine bio-waste, and their potential application in the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) who develop pulmonary embolism (PE) in the full spectrum of patient care settings need to be elucidated. The aim of this study was to compare the clinical characteristics, treatment, and 90-day outcomes in patients diagnosed with PE while recovering from COVID-19 in the outpatient setting versus those who were diagnosed with PE while being hospitalized with COVID-19. Data from the international Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry were used. The major study outcomes were all-cause death, major bleeding, and venous thromboembolism (VTE) recurrences during the first 90 days after PE. From March 2020 to March 2021, 737 patients with COVID-19 experienced acute PE. Of these, 340 (46%) were recovering from COVID-19 as outpatients (267 patients who had been treated at home for COVID-19 and 73 discharged after being hospitalized with COVID-19). Compared with inpatients with COVID-19, those recovering in the outpatient setting upon PE were less likely to be men (odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.40–0.72) and less likely to have hypertension (OR: 0.55; 95% CI: 0.41–0.74) or diabetes (OR: 0.51; 95% CI: 0.33–0.76). At 90-day follow-up, eight patients (none recovering from COVID-19 as outpatient vs. 2.4% of inpatients with COVID-19) developed recurrent VTE, 34 (1.9 vs. 7.9%) had major bleeding, and 128 (10 vs. 24%) died. On multivariable analysis, inpatients with COVID-19 were at a higher risk of major bleeding (adjusted hazard ratio [HR]: 6.80; 95% CI: 1.52–30.4) or death (adjusted HR: 2.24; 95% CI: 1.40–3.58). In conclusion, using a large multinational registry of patients with COVID-19 who experienced PE, thromboembolic episodes occurring in those recovering from COVID-19 as outpatients were associated with less ominous outcomes than inpatients with COVID-19. [ABSTRACT FROM AUTHOR]

Designing oral formulations for children is very challenging, especially considering their peculiarities and preferences. The choice of excipients, dosing volume and palatability are key issues of pediatric oral liquid medicines. The purpose of the present study is to develop an oral pediatric solution of a model bitter drug (ranitidine) following a patient centric design process which includes the definition of a target product profile (TPP). To conclude on the matching of the developed solution to TPP, its chemical and microbiological stability was analyzed over 30 days (stored at 4 °C and room temperature). Simulation of use was accomplished by removing a sample with a syringe every day. Taste masking was assessed by an electronic tongue. The developed formulation relied on a simple taste masking strategy consisting in a mixture of sweeteners (sodium saccharine and aspartame) and 0.1% sodium chloride, which allowed a higher bitterness masking effectiveness in comparison with simple syrup. The ranitidine solution was stable for 30 days stored at 4 °C. However, differences were noted between the stability protocols (unopened recipient and in-use stability) showing the contribution of the simulation of use to the formation of degradation products. Stock solution was subjected to acid and alkali hydrolysis, chemical oxidation, heat degradation and a photo degradation stability assessment. The developed pediatric solution matched the TPP in all dimensions, namely composition suitable for children, preparation and handling adapted to hospital pharmaceutical compounding and adequate stability and quality. According to the results, in-use stability protocols should be preferred in the stability evaluation of pediatric formulations. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a widely heterogeneous disease, and the natural history of patients with cancer-associated thrombosis may differ according to the cancer site. Lung cancer is the most common malignancy, and a leading cause of death. A number of studies in the literature suggest that patients with adenocarcinoma may have a worse outcome than those with squamous or other types of lung cancer. The aim of the current study was to assess the potential impact of lung cancer histology on the incidence rates of VTE recurrences, major bleeding, or death appearing during the course of anticoagulation, in patients with lung cancer and VTE. Our findings, obtained from a large series of consecutive patients with lung cancer and VTE (482 patients), reveal important differences between patients with adenocarcinoma vs. other histologies in their outcomes during anticoagulation. This might likely help to design better therapeutic strategies for patients with lung cancer. Background: In patients with lung cancer and venous thromboembolism (VTE), the influence of cancer histology on outcome has not been consistently evaluated. Methods: We used the RIETE registry (Registro Informatizado Enfermedad TromboEmbólica) to compare the clinical characteristics and outcomes during anticoagulation in patients with lung cancer and VTE, according to the histology of lung cancer. Results: As of April 2022, there were 482 patients with lung cancer and VTE: adenocarcinoma 293 (61%), squamous 98 (20%), small-cell 44 (9.1%), other 47 (9.8%). The index VTE was diagnosed later in patients with squamous cancer than in those with adenocarcinoma (median, 5 vs. 2 months). In 50% of patients with adenocarcinoma, the VTE appeared within the first 90 days since cancer diagnosis. During anticoagulation (median 106 days, IQR: 45–214), 14 patients developed VTE recurrences, 15 suffered major bleeding, and 218 died: fatal pulmonary embolism 10, fatal bleeding 2. The rate of VTE recurrences was higher than the rate of major bleeding in patients with adenocarcinoma (11 vs. 6 events), and lower in those with other cancer types (3 vs. 9 events). On multivariable analysis, patients with adenocarcinoma had a non-significantly higher risk for VTE recurrences (hazard ratio [HR]: 3.79; 95%CI: 0.76–18.8), a lower risk of major bleeding (HR: 0.29; 95%CI: 0.09–0.95), and a similar risk of mortality (HR: 1.02; 95%CI: 0.76–1.36) than patients with other types of lung cancer. Conclusions: In patients with lung adenocarcinoma, the rate of VTE recurrences outweighed the rate of major bleeding. In patients with other lung cancers, it was the opposite. [ABSTRACT FROM AUTHOR]

Background: For patients with suspected pulmonary embolism (PE), age- or clinically-adjusted D-dimer threshold level can be used to define a negative test that safely excludes PE and reduces the use of imaging. However, the utility of this approach in patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbation is undefined. Methods: We ran an analysis of the patients hospitalized for COPD exacerbation and randomized to the intervention in the SLICE trial. Using the conventional strategy as the reference, we compared the proportion of patients with a negative D-dimer result, and the negative predictive value and sensitivity of three D-dimer threshold strategies for initial PE or subsequent diagnosis of venous thromboembolism (VTE): the age-adjusted strategy, the Wells-adjusted strategy, and the YEARS-adjusted strategy. Results: We included 368 patients. Using a conventional threshold, 182 (49.5%) patients had negative D-dimer values, of whom 1 (0.6%) had PE (sensitivity, 94.1%). The use of an age-adjusted threshold increased the number of patients in whom PE could be excluded from 182 to 233 patients (63.3%), and the proportion of false-negative findings increased from 0.5% to 1.7% (sensitivity, 76.5%). With the use of the Wells or YEARS strategies, 64.4% and 71.5% had negative values, and the proportion of false-negative findings was 2.5% (sensitivity, 64.7%) and 2.7% (sensitivity, 58.8%), respectively. Conclusions: In patients hospitalized for COPD exacerbation, compared with the conventional strategy, age- or clinically-adjusted strategies of D-dimer interpretation were associated with a larger proportion of patients in whom PE was ruled out with a higher failure rate. Trial Registration: ClinicalTrials.gov number: NCT02238639. [ABSTRACT FROM AUTHOR]

The use of sunscreens is an established and recommended practice to protect skin from solar-induced damage. Around 30 UV filters can be used in sunscreen products in the European Union, which ought to follow the requirements of the regulation 1223/2009 to ensure their efficacy and safety for humans. Nevertheless, low photostability and putative toxicity for humans and environment have been reported for some UV filters. Particularly, the negative impact in marine organisms has recently raised concern on the scientific community. Therefore, it is important to develop new UV filters with improved safety profile and photostability. Over the last two decades, nearly 200 new compounds have revealed promising photoprotection properties. The explored compounds were obtained through different approaches, including exploration of natural sources, synthetic pathways, and nanotechnology. Almost 50 natural products and around 140 synthetic derivatives, such as benzimidazoles, benzotriazoles, hydroxycinnamic acids, xanthones, triazines, among others, have been studied aiming the discovery of novel, effective, and safer future photoprotective agents. Herein, we provide the reader with an overview about UV filters' challenges and prospects, offering a forward-looking to the next-generation of UV filters. [ABSTRACT FROM AUTHOR]

Sensitive skin is characterized by symptoms of discomfort when exposed to environmental factors. Peptides are used in cosmetics for sensitive skin and stand out as active ingredients for their ability to interact with skin cells by multiple mechanisms, high potency at low dosage and the ability to penetrate the stratum corneum. This study aimed to analyze the composition of 88 facial cosmetics for sensitive skin from multinational brands regarding usage of peptides, reviewing their synthetic pathways and the scientific evidence that supports their efficacy. Peptides were found in 17% of the products analyzed, namely: acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, acetyl tetrapeptide-15, palmitoyl tripeptide-5, acetyl hexapeptide-49, palmitoyl tetrapeptide-7 and palmitoyl oligopeptide. Three out of seven peptides have a neurotransmitter-inhibiting mechanism of action, while another three are signal peptides. Only five peptides present evidence supporting their use in sensitive skin, with only one clinical study including volunteers having this condition. Noteworthy, the available data is mostly found in patents and supplier brochures, and not in randomized placebo-controlled studies. Peptides are useful active ingredients in cosmetics for sensitive skin. Knowing their efficacy and synthetic pathways provides meaningful insight for the development of new and more effective ingredients. [ABSTRACT FROM AUTHOR]

[Display omitted] The nasal route has been investigated as a promising alternative for drug delivery to the central nervous system, avoiding passage through the blood–brain barrier and improving bioavailability. In this sense, it is necessary to develop and test the effectiveness of new formulations proposed for the management of neurological disorders. Thereby, the aim of this work was to develop and characterize an ion sensitive in situ hydrogel containing diazepam-loaded nanostructured lipid carriers (DZP-NLC) for nasal delivery in the treatment of epilepsy. Physical characterization of the developed formulations was performed and included the evaluation of rheological features, particle size, polydispersity index (PDI) and zeta potential (ZP) of an in situ hydrogel containing DZP-NLC. Afterwards, in vitro drug release, in vitro mucoadhesion and biocompatibility studies with RPMI 2650 nasal cells were performed. The in situ hydrogel containing DZP-NLC was aerosolized with a nasal spray device specifically designed for nose-to-brain delivery (VP7 multidose spray pump with a 232 N2B actuator) and characterized for droplet size distribution and spray cone angle. Finally, the deposition pattern of this hydrogel was evaluated in a 3D-printed human nasal cavity model. The developed in situ hydrogel containing DZP-NLC presented adequate characteristics for nasal administration, including good gelling ability, mucoadhesiveness and prolonged drug release. In addition, after inclusion in the hydrogel net, the particle size (81.79 ± 0.53 nm), PDI (0.21 ± 0.10) and ZP (-30.90 ± 0.10 mV), of the DZP-NLC remained appropriate for nose-to-brain delivery. Upon aerosolization in a nasal spray device, a suitable spray cone angle (22.5 ± 0.2°) and adequate droplet size distribution (Dv (90) of 317.77 ± 44.12 µm) were observed. Biocompatibility studies have shown that the developed formulation is safe towards RPMI 2650 cells in concentrations up to 100 μg/mL. Deposition studies on a 3D-printed human nasal cavity model revealed that the best nasal deposition profile was obtained upon formulation administration without airflow and at an angle from horizontal plane of 75°, resulting in 47% of administered dose deposited in the olfactory region and 89% recovery. The results of this study suggested that the intranasal administration of the developed in situ hydrogel containing DZP-NLC could be a promising alternative to the conventional treatments for epilepsy. [ABSTRACT FROM AUTHOR]

Objectives: The psychosocial impact of psoriasis is well documented. However, the contributing role of clinical disease characteristics is not satisfactorily explored. This study aimed to validate the Self-administered Psoriasis Area and Severity Index (SAPASI) to a Portuguese population (SAPASI-PT) and to perform its cross-validation, assessing how the results will generalize to an independent data set, with the Psoriasis Area and Severity Index (PASI), in order to assess the influence of psoriasis' severity on psychosocial disability and psychopathology.Methods: A cross-sectional study with 228 patients with psoriasis was carried out. Data was collected through a sociodemographic and clinical questionnaire, SAPASI-PT, the Psoriasis Disability Index (PDI) and the Brief Symptoms Inventory (BSI). The cultural and linguistic adaptation of SAPASI to a Portuguese version and the cross validation with PASI was carried out. Multiple associations between psychosocial disability, psychopathology and severity, discomfort and location of lesions were investigated through logistic regression models.Results: A good adjustment model for SAPASI-PT is found. Also, associations between psychosocial disability, psychopathology and the psoriasis severity and discomfort are found. The existence of lesions is positively associated with the severity of the disease. Patients with lesions in hands or genitals are those reporting a greater discomfort. The presence of lesions in hands is positively associated with PDI, i.e., with leisure and with treatment, marginally. Additionally, patients scoring higher in the personal dimension are found to have a significantly greater percentage of lesions in the genitals.Conclusions: The psoriasis severity and location of lesions are important determinants of patients´ quality of life. Lesions on face, hands and genitals are associated with a higher impact on psychosocial wellbeing of patients. Psychological counselling should be considered within psoriasis treatment context in patients with the described disease manifestations. [ABSTRACT FROM AUTHOR]

Polyphenols are a large family of natural compounds widely used in cosmetic products due to their antioxidant and anti-inflammatory beneficial properties and their ability to prevent UV radiation-induced oxidative stress. Since these compounds present chromophores and are applied directly to the skin, they can react with sunlight and exert phototoxic effects. The available scientific information on the phototoxic potential of these natural compounds is scarce, and thus the aim of this study was to evaluate the photoreactivity and phototoxicity of five phenolic antioxidants with documented use in cosmetic products. A standard ROS assay was validated and applied to screen the photoreactivity of the natural phenolic antioxidants caffeic acid, ferulic acid, p-coumaric acid, 3,4-dihydroxyphenylacetic acid (DOPAC), and rutin. The phototoxicity potential was determined by using a human keratinocyte cell line (HaCaT), based on the 3T3 Neutral Red Uptake phototoxicity test. Although all studied phenolic antioxidants absorbed UV/Vis radiation in the range of 290 to 700 nm, only DOPAC was able to generate singlet oxygen. The generation of reactive oxygen species is an early-stage chemical reaction as part of the phototoxicity mechanism. Yet, none of the studied compounds decreased the viability of keratinocytes after irradiation, leading to the conclusion that they do not have phototoxic potential. The data obtained with this work suggests that these compounds are safe when incorporated in cosmetic products. [ABSTRACT FROM AUTHOR]

The influence of the vehicle in topical treatment adherence remains to be elucidated. The aim of this study is to analyze the influence of the pharmaceutical dosage form on adherence to topical treatment in psoriasis patients, taking into consideration the mechanical features. The adherence was evaluated in a sample of 102 psoriasis patients, followed for approximately 45 days. Adherence was calculated with a new combined methodology using a log and medication weights. The effect of the group formulation was evaluated using logistic regression models. A complex effect of the vehicle on adherence was found, mediated by the affected area. The adherence was significantly higher for patients applying gels and creams than for those using ointments, whenever the body area affected was extensive. The opposite was found when the affected area was small. Mechanical properties can partially explain the findings since gels and creams may be easier to apply. Patient beliefs and preferences regarding vehicles and their sensory attributes might also explain the results. It is noteworthy that adherence was strikingly low, with more than 75% non-adherent patients. This real-world evidence provides an insight for pharmaceutical industries and guidance for treatment prescription by physicians aiming to address the public health emergency of treatment non-adherence. [ABSTRACT FROM AUTHOR]

The nasal route has been used for many years for the local treatment of nasal diseases. More recently, this route has been gaining momentum, due to the possibility of targeting the central nervous system (CNS) from the nasal cavity, avoiding the blood−brain barrier (BBB). In this area, the use of lipid nanoparticles, such as nanostructured lipid carriers (NLC) and solid lipid nanoparticles (SLN), in nasal formulations has shown promising outcomes on a wide array of indications such as brain diseases, including epilepsy, multiple sclerosis, Alzheimer's disease, Parkinson's disease and gliomas. Herein, the state of the art of the most recent literature available on in vitro studies with nasal formulations of lipid nanoparticles is discussed. Specific in vitro cell culture models are needed to assess the cytotoxicity of nasal formulations and to explore the underlying mechanism(s) of drug transport and absorption across the nasal mucosa. In addition, different studies with 3D nasal casts are reported, showing their ability to predict the drug deposition in the nasal cavity and evaluating the factors that interfere in this process, such as nasal cavity area, type of administration device and angle of application, inspiratory flow, presence of mucoadhesive agents, among others. Notwithstanding, they do not preclude the use of confirmatory in vivo studies, a significant impact on the 3R (replacement, reduction and refinement) principle within the scope of animal experiments is expected. The use of 3D nasal casts to test nasal formulations of lipid nanoparticles is still totally unexplored, to the authors best knowledge, thus constituting a wide open field of research. [ABSTRACT FROM AUTHOR]