Solid Lipid Nanoparticles Based on Babassu Oil and Copaiba Oleoresin: A Promising Approach for Prostate Cancer Therapy.

Solid lipid nanoparticles (SLNs) represent promising nanostructures for drug delivery systems. This study successfully synthesized SLNs containing different proportions of babassu oil (BBS) and copaiba oleoresin (COPA) via the emulsification-ultrasonication method. Before SLN synthesis, the identification and quantification of methyl esters, such as lauric acid and ß-caryophyllene, were performed via GC-MS analysis. These methyl esters were used as chemical markers and assisted in encapsulation efficiency experiments. A 22 factorial design with a center point was employed to assess the impact of stearic acid and Tween 80 on particle hydrodynamic diameter (HD) and polydispersity index (PDI). Additionally, the effects of temperature (8 ± 0.5 °C and 25 ± 1.0 °C) and time (0, 7, 15, 30, 40, and 60 days) on HD and PDI values were investigated. Zeta potential (ZP) measurements were utilized to evaluate nanoparticle stability, while transmission electron microscopy provided insights into the morphology and nanometric dimensions of the SLNs. The in vitro cytotoxic activity of the SLNs (10 µg/mL, 30 µg/mL, 40 µg/mL, and 80 µg/mL) was evaluated using the MTT assay with PC-3 and DU-145 prostate cancer cell lines. Results demonstrated that SLNs containing BBS and COPA in a 1:1 ratio exhibited a promising cytotoxic effect against prostate cancer cells, with a percentage of viable cells of 68.5% for PC-3 at a concentration of 30 µg/mL and 48% for DU-145 at a concentration of 80 µg/mL. These findings underscore the potential therapeutic applications of SLNs loaded with BBS and COPA for prostate cancer treatment.

Exposure to Smartphones and Tablets, Physical Activity and Sleep in Children From 5 to 10 Years Old: A Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to verify the association between smartphone/tablet exposure and physical activity and sleep in children from 5 to 10 years old. Data Source: This study followed the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and included studies that met eligibility criteria based on the "PECO" strategy: participants (children from 5 to 10 years old), exposure (smartphone and tablet use), and outcome (physical activity and sleep). STUDY INCLUSION AND EXCLUSION CRITERIA: The inclusion criteria were observational studies published in indexed scientific journals and written in Portuguese, English, and Spanish that verified the association of exposure to smartphones/tablets with physical activity and sleep in children aged 5 to 10 years of both sexes. Studies were considered eligible only if they met the previous criteria. Data Extraction: The search was conducted in January 2023 on databases from electronic journals without the restriction of the period. To meta-analyze were extracted and grouped using models of fixed and random effects, the coefficients Odds Ratio (OR), Beta (ß), Standard Error (SE), and Confidence Intervals of 95% (95%CI). Data Synthesis: 2396 potentially relevant papers were identified, and 17 met the inclusion criteria. RESULTS: It can be verified that there was an inverse association between smartphones with physical activity and sleep. Studies indicate that for every additional hour of smartphone and tablet use, sleep can be expected to decrease by an average of 11 minutes (ß = - 0.11; 95%CI = -0.13; -0.09). Children using smartphones and tablets were 1.79 times (OR = 1.79; 95%CI = 1.72-1.86) more likely to have shorter sleep duration and 1.53 times (OR = 1.53; 95%CI = 1.41-1.65) more likely to have worse sleep quality. Children with shorter smartphone and tablet usage were 1.19 times more likely to be active (OR = 1.19; 95% CI = 1.03-1.37). CONCLUSION: Children of 5 to 10 years who are more often exposed to smartphones and tablets are prone to have worse quality and quantity of sleep, as well as less practice of physical activity. Health promotion actions can be encouraged based on the results, aiming to reduce the use time of these devices and improve children's health and quality of life.

Discovery of a new pyrido[2,3-d]pyridazine-2,8-dione derivative as a potential anti-inflammatory agent through COX-1/COX-2 dual inhibition.

In this paper, we present the design and synthesis of a novel series of pyrido[2,3-d]pyridazine-2,8-dione derivatives via the annulation of the 2-pyridone pattern. The synthesized derivatives were evaluated for in vivo anti-inflammatory activity using an ear edema model. Compound 7c, which showed a greater inhibition of ear edema (82%), was further tested for its in vitro COX-1/COX-2 inhibitory activity. Compound 7c showed similar inhibitory activities against COX-1 and COX-2 isoenzymes. The structural features that ensure the dual inhibition of COX-1 and COX-2 were elucidated using molecular docking studies. Overall, the ring closing of 2-pyridone pattern I transformed this highly selective COX-2 inhibitor into a dual COX inhibitor (7c), which could serve as a model for determining selectivity for COX-2.

Chenopodium Ambrosioides Linn Mitigates Bone Loss in Rats with Periodontitis.

Statement of the Problem: Periodontitis is an inflammatory disease that causes bone loss. Some patients do not respond well to the classic treatment and need therapies that minimize bone loss, the main sequel of the disease. Chenopodium ambrosioides L. has stood out due to its anti-inflammatory and anti-oxidative activities. However, no study has yet investigated its effect on periodontitis. Purpose: This study aimed to evaluate the bone protective effect of Chenopodium ambrosioides L. (CAL) extract on ligature-induced periodontitis model in rats. Materials and Method: For this, a pre-clinical assay was performed, using male Wistar rats divided into 3 groups: Naive (N) (n=6), not submitted to any procedure; Saline (SAL) (n=6), submitted to ligature-induced periodontitis and receiving 2 ml/kg of 0.9% saline solution; and CAL extract, which was subdivided into 3 subgroups (n=6/subgroup) receiving the CAL at 3 (CAL3), 10 (CAL10) or 30 mg/kg (CAL30). All agents were given, by oral gavage, 30 min before periodontitis induction and daily until euthanasia (11th day). By then, maxillae were removed for macroscopic, histological, and histometric analyses. Kidneys, liver, and stomach were collected to evaluate the safety of CAL extract. High-performance liquid chromatography (HPLC) assay was used to investigate the flavonoid content in the extract. Results: Chenopodium ambrosioides L. extract at 30mg/kg showed a reduction by 58% in bone loss marked by an increase (+35%) in the number of osteoblasts and a reduction (-51%) on the number of osteoclasts (p< 0.05). No significant alteration in the liver, kidney, or stomach was seen. Rutin was the main flavonoid found. Conclusion: In summary, it was observed that Chenopodium ambrosioides L. extract has shown important anti-inflammatory and bone anabolic and anti-resorptive properties without causing toxicity in the main organs. Rutin, as the main flavonoid of the extract, seems to be responsible for the beneficial effect of this agent.

From moral rights to legal rights? Lessons from healthcare contexts.

Many believe the existence of a moral right to some good should lead to recognition of a corresponding legal right to that good. If, for instance, there is a moral right to healthcare, it is natural to believe countries should recognize a legal right to healthcare. This article demonstrates that justifying legal rights to healthcare is more difficult than many assume. The existence of a moral right is insufficient to justify recognition of a corresponding justiciable constitutional right. Further conditions on when it is appropriate to recognize constitutional rights are rarely satisfied in the healthcare case. And focusing on aspirational or statutory rights presents costs for those seeking to justify legal rights on the basis of corresponding moral ones while maintaining empirical challenges for justifying constitutional rights. This suggests movement from a moral right to a corresponding legal one is far from straightforward and justifies examining alternative means of realizing moral socio-economic rights such as the proposed moral right to healthcare.

Clustering of health risk behaviors in pregnant individuals: Data from the Brazilian risk factor surveillance system for non-communicable chronic diseases.

OBJECTIVE: To investigate the clustering of health risk behaviors (HRB) and its association with demographics, physical exercise, overweight, perception of health, and diseases in Brazilian pregnant people. STUDY DESIGN: This is a cross-sectional study using data from the Risk Factor Surveillance System for Non-communicable Chronic Diseases by Telephone Survey (VIGITEL), the main health survey in Brazil. METHODS: We used data on fruit and vegetable consumption, TV time, tobacco, and alcohol abuse in individuals who reported being pregnant (n = 4553). We used latent class analysis to identify optimal HRB clustering among participants. Multinomial regression (odds ratio [OR] and 95% confidence intervals [95%CI]) was applied to identify factors associated with HRB cluster. RESULTS: Three clustering classes were identified: "without HRB cluster" (i.e., least unhealthy behaviors) (n = 2402, 52,8%), "moderate HRB cluster" (n = 1983, 43,5%), and "high HRB cluster" (i.e., most unhealthy behaviors) (n = 168, 3,7%). Pregnant people aged 35-50 years (OR = 1.89, 95%CI = 1.01; 3.52) who did not practice physical exercise (OR = 1.94, 95%CI 1.11; 3.39) were more likely to be classified as "high HRB cluster". Participants with 9-11 years (OR = 0.11, 95%CI = 0.07; 0.17) and ≥ 12 (OR = 0.05, 95%CI = 0.02; 0.11) years of education had a lower likelihood of being in the "high HRB cluster". CONCLUSION: Three HRB clustering patterns were found in this study. Greater maternal age, low education, and absence of physical exercises increased the chances of being in the high HRB cluster group. Participants with higher educational levels were less likely to be in the High HRB cluster.

Do patients with obesity undergoing bariatric surgery modify their objectively measured physical activity? A systematic review and meta-analysis.

BACKGROUND: Obesity is a chronic disease associated with adverse outcomes and its prevalence is increasing, which makes it a concern. One of the obesity treatment options is bariatric surgery, which effectively reduces calorie absorption and total body mass, but its effects on physical activity (PA) levels need to be clarified, considering the protective effect of the PA against cardiovascular disease, independently of the weight loss alone. OBJECTIVES: To carry out a systematic review and meta-analysis of observational studies that evaluated PA in pre- and post-bariatric surgery periods through objective evaluation. METHODS: A systematic search was carried out following the PRISMA criteria of studies with adult individuals who underwent bariatric surgery and were objectively evaluated for PA pre- and post-surgery. Studies with interventions were excluded. RESULTS: A total of 419 records were found, and after excluding duplicates and applying the eligibility criteria, 10 studies remained. This meta-analysis found a significant increase in the steps by day (MD = 1340; 95% CI = 933.90; 1745.35, p < 0.001) and the light physical activity level (MD = 16.8 min/day; 95% CI = 2.60; 30.98, p = 0.02), but not in moderate to vigorous physical activity (MD = 0.24; 95% CI = -0.08; 1.57, p = 0.92). CONCLUSIONS: Patients undergoing bariatric surgery increased their steps by day and light physical activity but did not increase moderate to vigorous physical activity.

Use of medicinal plants during COVID-19 pandemic in Brazil.

Medicinal plants are an integrative and complementary health practice widely used by the population. However, its use is not without risks. This study assessed the profile and associated factors with the traditional use of medicinal plants. To this end, a cross-sectional survey study was conducted in a southeastern Brazilian city. Descriptive analysis was performed by frequency distribution and median and interquartile range. Associated factors with the use of medicinal plants were analyzed using Poisson regression with robust variance. A total of 641 people were interviewed, of whom 258 (40.2%) reported using medicinal plants. A total of 79 distinct plants were identified, of whom Melissa officinalis (31.0%), Peumus boldus (24.4%), Mentha spicata (20.9%), Matricaria recutita L. (18.2%), Rosmarinus officinalis (17.0%), and Foeniculum vulgare (14.7%) were the most used. There were no reports of medicinal plants used to treat COVID-19. However, anxiety was the most frequently cited indication for using medicinal plants, a health condition exacerbated by the COVID-19 pandemic. Furthermore, the use of medicinal plants for treating respiratory and gastrointestinal symptoms similar to those in COVID-19 has been identified. There was an association between the use of medicinal plants and females, non-white, lower schooling, higher income, and comorbidities.

Abusive use of Zolpidem as a Result of COVID-19 and Perspectives of Continuity of the Problem in the Post-Pandemic Period.

Zolpidem is a non-benzodiazepine hypnotic drug that works as a positive modulator of Gamma-Amino Butyric Acid-A (GABA-A) receptors, with high selectivity for α1 subunits. Given this selective binding, the drug has a strong hypnotic activity. Social isolation during the SARS-CoV-2 pandemic has contributed to increased rates of anxiety, depression, and insomnia. As a result, studies have pointed to a possible increase in the indiscriminate use of drugs with sedative effects, such as Zolpidem, during the pandemic. The aim of this work was to present prospective evidence that warns of the possibility of the abusive use of Zolpidem even after the pandemic. High rates of addiction to this drug have been reported around the world after the emergence of the coronavirus. Data from the National Survey on Drug Use and Health and from Medicaid support the continuing growth in prescription and indiscriminate use of Zolpidem during the pandemic and afterward. Therefore, there is enough evidence to support the indiscriminate use of this drug since the beginning of the pandemic. Rates of indiscriminate use of sedatives may continue to increase in the post-pandemic period, especially if strict control measures are not taken by health authorities.

Factors associated with Alzheimer's disease prevalence and mortality in Brazil-An ecological study.

A few epidemiological studies are evaluating the prevalence and mortality rates of Alzheimer's disease, with no one using a nationwide sample of Brazilian elderlies. This study aims to calculate the prevalence of Alzheimer's disease and investigate possible associations with sociodemographic and lifestyle factors and the presence of diseases non-communicable, and the prevalence and mortality for all Brazilian state capitals. This is an ecological design study made with secondary public data provided by the Ministry of Health. Prevalence rates were calculated based on the analysis of the dispensing of Alzheimer's disease-specific drugs. Correlation analyzes were performed between rates and factors, and a multiple linear regression analysis was used to analyze possible associations between variables, controlled for each other. AD prevalence was 313/100,000. Prevalence rates were positively associated with primary health care coverage factors and negatively associated with ultra-processed food consumption and physical activity levels. AD mortality was 98/100,000. Mortality rates were positively associated with the proportion of obese elderly and elderly living on up to half the minimum wage and were inversely associated with the proportion of elderly with diabetes factors. We found positive and negative associations of sociodemographic, behavioral and diabetes indicators with Alzheimer's disease prevalence and mortality, which provide data that can be investigated by studies with different designs.

Controlled Pyrazole-Hydrazone Annulation: Regiodivergent Synthesis of 1H- and 2H-Pyrazolo[3,4-d]pyridazinones.

An efficient and controlled site-selective annulation of 3,5-diethoxycarbonyl 4-hydrazonyl pyrazoles is described. The relative proportion of the products is affected by hydrazone intermediate configuration, reaction temperature, and Lewis acid employed. At a temperature of 110-120 °C, the reaction preferentially afforded 1H-pyrazolo[3,4-d]pyridazin-7(6H)-ones, whereas using Yb(OTf)3 in MeCN reflux, 2H-pyrazolo[3,4-d]pyridazin-7(6H)-ones were favored. Computational investigations were performed to clarify the mechanism and the origin of the regiodivergence.

Is Binge Drinking Associated With Specific Types of Exercise and Free Time Sports? A Pooled Analysis With 718,147 Adults.

OBJECTIVE: To verify the association between exercise and free time sport types and binge drinking in a large sample of adults. METHODS: Data of 718,147 adults from the "Surveillance of Risk and Protection Factors for Chronic Diseases by Telephone Survey" were used. We described the demographic and behavioral variables, and negative binomial regression analyzed the association between exercise and free time sport types and binge drinking adjusted by demographics variables, body mass index status, and television time. RESULTS: Outdoor walking/running was the most common exercise reported (20.0%, 95% confidence interval [CI], 19.8%-20.2%), followed by team sports (8.1%; 95% CI, 8.0%-8.2%) and strengthening (8.0%; 95% CI, 7.9%-8.1%). The prevalence of binge drinking for each exercise and free time sport type ranged from 6.9% (water aerobics) to 31.9% (team sports). Participants engaging in strengthening (prevalence ratio = 1.12; 95% CI, 1.04-1.21, P = .002) and team sports (prevalence ratio = 1.11; 95% CI, 1.07-1.17, P < .001) were more likely to binge drink more frequently in the past 30 days than inactive participants. CONCLUSIONS: It appears that the participants' profile plays an important role in the underlying social context of this association. Participants with more frequent strengthening and less frequent team sports practice, who were primarily younger and single, were more likely to binge drink frequently.

Self-Medication during the COVID-19 Pandemic in Brazil: Findings and Implications to Promote the Rational Use of Medicines.

Self-medication is identified by the consumption of medications without a prescription or guidance from a qualified prescribing professional. This study estimated the prevalence, profile, and associated factors with self-medication during the COVID-19 pandemic in Brazil. A cross-sectional study was conducted through a household survey in the Alegre city, from November to December 2021. Descriptive analysis was performed for the sociodemographic and clinical characteristics of the interviewees. Poisson regression with robust variance was used to identify the association of sociodemographic and clinical variables with self-medication. A total of 654 people were interviewed, of whom 69.4% were self-medicating. The younger age group (PR = 1.13; 95% CI = 1.01-1.26), female gender (PR = 1.19; 95% CI = 1.04-1.37), consumption of alcoholic beverages (PR = 1.13; 95% CI = 1.01-1.25), and problems with adherence to pharmacological treatment (PR = 1.15; 95% CI = 1.04-1.28) were associated with self-medication, while the occurrence of polypharmacy (PR = 0.80; 95% CI = 0.68-0.95) was a protective factor for self-medication. Self-medication was directly related to over-the-counter drugs, with analgesics dipyrone and paracetamol being the most commonly used. Self-medication consumption of prescription drugs, including those under special control, was identified to a lesser extent.

The Relationship between Physical Activity, Sleep Quality, and Stress: A Study of Teachers during the COVID-19 Pandemic.

The COVID-19 pandemic prompted chaotic changes in the daily lives of K-12 teachers, resulting in increased stress and other mental health problems. Limited evidence regarding the relationship between physical activity, sleep, and perceived stress among teachers during the COVID-19 pandemic exists. Therefore, the purpose of this study was to investigate the association between physical activity, sleep quality, and perceived psychological stress among teachers during the COVID-19 pandemic. An online survey measuring physical activity, sleep quality, and perceived psychological stress was distributed across 47 US states between September and October of 2020. Data provided by 635 teachers (mean age: 42 ± 18 years, 74.6% female) were included in the present analysis. Results suggested a negative association between physical activity and perceived psychological stress. Mediation analyses indicated that teachers engaging in high levels of physical activity were more likely to have good quality sleep and, in turn, were less likely to report high levels of perceived stress. Physical activity and sleep-related interventions could help curtail the rising levels of psychological distress amongst K-12 teachers during stressful times such as the COVID-19 pandemic. Teachers, especially those that self-report as female and/or young, report high levels of stress. These high levels of stress are a serious challenge for school districts in terms of attracting and retaining qualified teachers in K-12 classrooms.

Daridorexant for the treatment of insomnia disorder: findings and implications.

PURPOSE: The involvement of the orexin system in the physiopathology of insomnia has been rapidly increasing in understanding. In this sense, daridorexant was the third orexin receptor antagonist approved by the FDA in January 2022. This review aims to summarize the chemistry, pharmacodynamics, pharmacokinetics, efficacy, safety, and tolerability profile of daridorexant for the treatment of insomnia disorder. METHODS: We performed a review of daridorexant for the treatment of insomnia disorder. The search was carried out in Medline via PubMed, Embase, and clinical trials, up to March 2022. RESULTS: Daridorexant 25 and 50 mg had more significant improvement for the wake after sleep onset (WASO), latency to persistent sleep (LPS), and subjective total sleep time (sTST) than placebo. In addition, daridorexant 50 mg was better for Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) than placebo. The most common adverse events were nasopharyngitis and headache. CONCLUSION: Daridorexant was efficacious and safe. Studies that evaluate the long-term safety and compare daridorexant with benzodiazepines, benzodiazepine receptor agonists, sedative antidepressants, and other orexin receptor antagonists are required.

Abdeg technology for the treatment of myasthenia gravis: efgartigimod drug experience.

INTRODUCTION: Myasthenia gravis is characterized by fluctuating muscle weakness that improves with rest and worsens with effort or throughout the day. AREAS COVERED: Efgartigimod is a human IgG1-derived Fc fragment modified at five residues to increase its affinity for the neonatal Fc receptor by Abdeg technology. Thus, efgartigimod binds to the neonatal Fc receptor and decreases the levels of IgG, including autoantibodies of this isotype. For acetylcholine receptor (AChR) antibody-positive patients, efgartigimod had a higher proportion of MG-ADL responders than placebo in the first treatment cycle. The mean changes of multiple outcomes from baseline were better for efgartigimod than placebo from weeks 1 to 7 in the first treatment cycle. The decrease of IgG and AChR autoantibodies was 61.3% and 57.6% one week after the first treatment cycle ends, respectively. The most common adverse events were headache, nasopharyngitis, nausea, and diarrhea, which occurred in the same proportion in the efgartigimod and placebo groups. Urinary and upper respiratory tract infections were twice as frequent in efgartigimod-treated patients. EXPERT OPINION: Efgartigimod was efficacious and safe for generalized myasthenia patients with AChR antibody-positive patients. These findings need to be confirmed in AChR antibody-negative patients, and long-term safety studies are currently ongoing.

Myasthenia gravis patients have a high level of autoantibodies, which can cause fluctuating muscle weakness. In this regard, efgartigimod is a new drug approved to treat myasthenia gravis that decreases antibody levels and symptom improvement. Furthermore, this drug was safe for these patients.[Figure: see text].

Regulating the Safety of Health-Related Artificial Intelligence.

This article analyzes whether Canada's present approach to regulating health-related artificial intelligence (AI) can address relevant safety-related challenges. Focusing primarily on Health Canada's regulation of medical devices with AI, it examines whether the existing regulatory approach can adequately address general safety concerns, as well as those related to algorithmic bias and challenges posed by the intersections of these concerns with privacy and security interests. It identifies several issues and proposes reforms that aim to ensure that Canadians can access beneficial AI while keeping unsafe products off Canadian markets and motivating safe, effective use of AI products for appropriate purposes and populations.

Regiodivergent Synthesis of 3,4- and 4,5-Disubstituted N-Methylpyrazoles from 4-Acyl-1H-pyrrole-2,3-dione and Methylhydrazine.

A simple, efficient and highly regioselective method for the preparation of 3,4- and 4,5-disubstituted N-methylpyrazoles in a one-pot procedure is reported. The methodology developed was based on the regiochemical control of the reaction of 4-acyl-1H-pyrrole-2,3-diones and methylhydrazine with an influence of the addition or absence of acid and the substrate structure.

Legal concerns in health-related artificial intelligence: a scoping review protocol.

BACKGROUND: Medical innovations offer tremendous hope. Yet, similar innovations in governance (law, policy, ethics) are likely necessary if society is to realize medical innovations' fruits and avoid their pitfalls. As innovations in artificial intelligence (AI) advance at a rapid pace, scholars across multiple disciplines are articulating concerns in health-related AI that likely require legal responses to ensure the requisite balance. These scholarly perspectives may provide critical insights into the most pressing challenges that will help shape and advance future regulatory reforms. Yet, to the best of our knowledge, there is no comprehensive summary of the literature examining legal concerns in relation to health-related AI. We thus aim to summarize and map the literature examining legal concerns in health-related AI using a scoping review approach. METHODS: The scoping review framework developed by (J Soc Res Methodol 8:19-32, 2005) and extended by (Implement Sci 5:69, 2010) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) guided our protocol development. In close consultation with trained librarians, we will develop a highly sensitive search for MEDLINE® (OVID) and adapt it for multiple databases designed to comprehensively capture texts in law, medicine, nursing, pharmacy, other healthcare professions (e.g., dentistry, nutrition), public health, computer science, and engineering. English- and French-language records will be included if they examine health-related AI, describe or prioritize a legal concern in health-related AI or propose a solution thereto, and were published in 2012 or later. Eligibility assessment will be conducted independently and in duplicate at all review stages. Coded data will be analyzed along themes and stratified across discipline-specific literatures. DISCUSSION: This first-of-its-kind scoping review will summarize available literature examining, documenting, or prioritizing legal concerns in health-related AI to advance law and policy reform(s). The review may also reveal discipline-specific concerns, priorities, and proposed solutions to the concerns. It will thereby identify priority areas that should be the focus of future reforms and regulatory options available to stakeholders in reform processes. TRIAL REGISTRATION: This protocol was submitted to the Open Science Foundation registration database. See https://osf.io/zav7w .