Extracellular vesicles release from protozoa parasite and animal model.

Diseases caused by protozoan parasites, such as leishmaniasis, trypanosomiasis, and malaria, are highly complex and together continue to cause high annual morbidity and mortality. The search for new compounds in environmental biodiversity, repositioning known drugs, and developing vaccines using old and innovative technologies have been employed to discover vaccines and new and alternative treatments. Extracellular vesicles (EVs) can carry parasite antigens, creating a new possibility to develop an effective and affordable platform for treatment, vaccines, and drug delivery. Thus, the evaluation of EVs in animal models can and should be explored among the countless biomedical applications. Herein, we will address the concept of EVs, their acquisition and characterization in protozoan parasite models, and the primary studies using these vesicles in therapeutic applications.

Intranasal administration of dextran-pramlintide polyelectrolyte complex-coated nanoemulsions improves cognitive impairments in a mouse model of Alzheimer's disease.

Nasal delivery has emerged as a non-invasive route to administer drugs for brain delivery. In particular, polyelectrolyte complexes-based nanocarriers have been demonstrated to be advantageous for nasal delivery of peptide drugs and vaccines. Pramlintide (Pram) is a peptide that emerges as a novel neuroprotective strategy to modify the pathogenesis of Alzheimer's disease (AD). In this study, we examined the effects of the intranasal administration of dextran-pramlintide polyelectrolyte complex-coated nanoemulsions (PEC-NEDexS/Pram) in an experimental model of AD induced by intracerebroventricular (i.c.v.) infusion of amyloid-beta (Aß1-42) peptide in mice. PEC-NEDexS/Pram displayed droplet size lower than 200 nm and a negatively charged surface. The locomotor activity of the animals was not affected by the i.c.v. Aß1-42 injection or Pram treatment. On the other hand, the intranasal administration of PEC-NEDexS/Pram at a dose of 100 µg/day for 14 consecutive days restored the impairment induced by Aß1-42 injection in the discriminative learning and the short-term spatial reference memory of mice. However, Pram treatment did not alter the Aß1-42-induced anhedonic behavior, oxidative stress parameters, or the pre-synaptic SNAP-25 and post-synaptic PSD-95 levels in the hippocampus and prefrontal cortex. These findings indicate cognitive-enhancing properties of intranasal Pram administration in an animal model of AD.

Characterization of newborn gut microbiota according to the pre-gestational maternal nutritional status and delivery mode.

PURPOSE: The aim of this study is to characterize the composition of the newborn gut microbiota based on the maternal pre-pregnancy nutritional status and the delivery mode. METHODS: A biological sample was collected from the anal mucosa of the newborns between 24 and 48 h after delivery, as it was not possible to collect a meconium sample at that time. A general data collection questionnaire was administered. The microbiome of the samples was analyzed by next-generation sequencing of the hypervariable regions v3-v4 of the 16S gene. Alpha diversity analyses were performed using the Observed Richness and Shannon diversity index metrics and Beta diversity analyses were conducted using Nonmetric multidimensional scaling with Weighted Unifrac, Differential abundance analysis was performed using a Negative Binomial Wald Test with maximum likelihood estimation for coefficients of Generalized Linear Models. RESULTS: Newborns of obese mothers exhibited lower alpha diversity compared to newborns of mothers with adequate BMI (body mass index). We observed variation in the composition of the microbial community in newborn stool samples, both from mothers with overweight/obesity and those with adequate pre-pregnancy BMI. We observed a visible correlation between the mode of delivery and the newborn's microbiota. We found variation in the overall composition of the microbial community in the stools of newborns, regardless of the delivery mode. CONCLUSIONS: The results of our study demonstrate differences in the microbiota of neonates born via cesarean section compared to those born vaginally as well as differences in newborns of mothers with overweight/obesity compared to those with an adequate pre-pregnancy BMI.

Doxorubicin and 4-nitrochalcone loaded in beeswax-based nanostructured lipid carriers: In vitro antitumoral screening and evaluation of synergistic effect on HepG-2 cells.

Cancer is the second most deadly disease worldwide, and the most traditional approaches such as chemotherapy still face limitations associated to drug dosage and off-target side effects. To address these issues, we propose the simultaneous administration of 4-Nitrochalcone (4NC) and Doxorubicin (DOX) using beeswax based nanostructured lipid carriers (NLCs). The co-encapsulation of 4NC and DOX in the beeswax based NLCs was performed using the water/oil/water double emulsion technique in association with the melt dispersion approach. The system composed by semi-spherical NLCs with an average diameter around 200 nm and narrow size distribution, displayed colloidal stability before and after redispersion, keeping the zeta potential below -30 mV. The antitumor activity of the nanoparticles was screened on different tumor cell lines, and the induced cellular death and internal ROS levels were analyzed on hepatocarcinoma cells, which were found to be more affected by the combination of 4NC and DOX. The results indicated that 4NC + DOX-NCLs could promote cytotoxicity and oxidative damage-mediated apoptosis in a HepG-2 cell line.

Graphene Quantum Dots from Natural Carbon Sources for Drug and Gene Delivery in Cancer Treatment.

Cancer therapy is constantly evolving, with a growing emphasis on targeted and efficient treatment options. In this context, graphene quantum dots (GQDs) have emerged as promising agents for precise drug and gene delivery due to their unique attributes, such as high surface area, photoluminescence, up-conversion photoluminescence, and biocompatibility. GQDs can damage cancer cells and exhibit intrinsic photothermal conversion and singlet oxygen generation efficiency under specific light irradiation, enhancing their effectiveness. They serve as direct therapeutic agents and versatile drug delivery platforms capable of being easily functionalized with various targeting molecules and therapeutic agents. However, challenges such as achieving uniform size and morphology, precise bandgap engineering, and scalability, along with minimizing cytotoxicity and the environmental impact of their production, must be addressed. Additionally, there is a need for a more comprehensive understanding of cellular mechanisms and drug release processes, as well as improved purification methods. Integrating GQDs into existing drug delivery systems enhances the efficacy of traditional treatments, offering more efficient and less invasive options for cancer patients. This review highlights the transformative potential of GQDs in cancer therapy while acknowledging the challenges that researchers must overcome for broader application.

Development and evaluation of nanostructured systems for cutaneous delivery of H2S-releasing corticosteroids for skin inflammatory diseases.

Psoriasis is an immune-mediated chronic inflammatory disease that causes major psychosocial impact. Topical corticosteroids represent the standard pharmacological treatment for mild-to-moderate disease, but their local and systemic adverse effects reinforce the need for treatment innovations. Here we developed lamellar phase-based formulations for topical delivery of a hybrid dexamethasone and hydrogen sulfide (H2S) donor molecule (Dexa-TBZ), aiming to potentiate the effects of the glucocorticoid with H2S. They offer the possibility to obtain precursor formulations free of water that originate lamellar phases upon water addition, preventing drug hydrolysis during storage. Two groups of formulations were developed varying the surfactants and oil phase types and content. Systems containing 20 and 70 % of water formed, respectively, bulk lamellar phase and a more fluid formulation consisting of dispersed droplets (< 1000 nm) stabilized by lamellar phase. Both presented pseudoplastic behavior. Dexa-TBZ was incorporated at 1 %, remaining stable for 8 h. Drug content decreased to ∼80 % after 1 week in precursor formulations free of water, but remained stable after that. Without causing changes to the cutaneous barrier function ex vivo or to the histological structure of the skin in vivo, the formulation containing phosphatidylcholine as surfactant and 70 % of water promoted 1.8- and 2.7-fold increases in Dexa-TBZ penetration in the stratum corneum and epidermis+dermis, respectively, compared to a control solution, demonstrating their potential applicability as topical delivery systems.

Association of birth and periodontal disease in Bolivia, Chile and Colombia / Asociación de parto prematuro y enfermedad periodontal en Bolivia, Chile y Colombia

ABSTRACT Introduction. Preterm birth is a major medical, social, and economic problem that causes a large proportion of neonatal mortality and morbidity, has a high impact on the healthcare system, and affects family quality of life. The weight of newborns with mothers with periodontal disease is significantly lower compared to mothers not affected by this oral disease. This adverse outcome is considered a global public health problem based on epidemiological data. Objective. To determine the association between the prevalence of preterm births and periodontal disease in Bolivia, Chile, and Colombia from 2000 to 2020. Materials and methods. This ecological study considered the population of women in Bolivia, Chile, and Colombia, according to the prevalence of preterm births and periodontal disease discriminated by age. The study covered the period between 2000 and 2020. The search strategy within the Institute for Health Metrics and Evaluation investigative tool included prevalence, age groups, causes of preterm births and periodontal disease, context and locations, women, and rates. Statistical analysis included a simple linear regression between preterm births and periodontal disease for each age group within each country. Results. Preterm birth rates were higher in the 15-19 years age group (Bolivia: 697,563; Chile: 844,864; Colombia: 804,126). The periodontal disease prevalence increased with age, as we observed in the 45-49 years group (Bolivia: 22,077,854; Chile: 34,297,901, Colombia: 32,032.830). According to age groups, the linear regression was statistically significant (p < 0.001) in all age groups for the Bolivian population over 30 years for the Colombian, and only in the 15-19 years group for the Chilean women. Conclusion. An association was found between preterm births and periodontal disease in all age groups in Bolivia, only in the group of 15 to 19 years in Chile, and 30 years and up in Colombia over the 20-year period.

RESUMEN Introducción. El parto prematuro es un problema médico, social y económico importante, causa gran mortalidad y morbilidad neonatal, tiene un impacto importante en el sistema de salud y afecta la calidad de vida de las familias. El peso de los recién nacidos de madres con enfermedad periodontal es significativamente menor en comparación con los de madres no afectadas por esta enfermedad bucal. Este resultado adverso se considera un problema de salud pública global según los datos epidemiológicos. Objetivo. Determinar la asociación entre la prevalencia de parto prematuro y la enfermedad periodontal en Bolivia, Chile y Colombia entre el 2000 y el 2020. Materiales y métodos. Este estudio ecológico consideró las poblaciones de mujeres de Bolivia, Chile y Colombia, y la prevalencia de partos prematuros y enfermedad periodontal, discriminadas por grupos de edad. El estudio abarcó el período entre el 2000 y el 2020. La estrategia de búsqueda con la herramienta de investigación del Institute for Health Metrics and Evaluation incluyó prevalencia, grupos de edad, años entre 2000 y 2020, causas de parto prematuro y enfermedad periodontal, contexto y ubicaciones, mujeres y tasas. El análisis estadístico incluyó una regresión lineal simple entre parto prematuro y enfermedad periodontal para cada grupo de edad dentro de cada país. Resultados. Las tasas de partos prematuros fueron mayores en el grupo de 15 a 19 años (Bolivia: 697.563, Chile: 844.864, Colombia: 804.126). La prevalencia de la enfermedad periodontal aumentó con la edad, particularmente en el grupo de 45 a 49 años (Bolivia: 22'077.854, Chile: 34'297.901, Colombia: 32'032,830). Según los grupos de edad, la regresión lineal fue estadísticamente significativa (p < 0,001) para todos los grupos evaluados de la población boliviana, en los grupos mayores de 30 años para las colombianas y solo en el grupo de 15 a 19 años para las mujeres chilenas. Conclusión. Se encontró asociación entre el parto prematuro y la enfermedad periodontal en todos los grupos de edad en Bolivia, solo en el grupo de 15 a 19 años en Chile, y de 30 años y más en Colombia en el período evaluado de 20 años.

Effect of iontophoresis on dacarbazine cutaneous delivery for melanoma topical treatment.

Dacarbazine (DTIC) is the drug of choice for melanoma treatment, but its systemic administration is related to several adverse effects. Here, DTIC topical delivery stimulated by iontophoresis is proposed to overcome such drawbacks. Hence, this work analyzed the impact of anodal iontophoresis on DTIC cutaneous delivery to provide an innovative topical alternative for melanoma treatment. The electrical stability of the drug was evaluated prior to the iontophoretic experiments, which demonstrated the need to add an antioxidant to the drug formulation. DTIC cutaneous permeation was evaluated in vitro for 6 h using three current densities (0.10, 0.25, and 0.50 mA/cm2). In addition, the effect of DTIC against skin cancer cells (MeWo and WM164) was investigated for 72 h of exposure to the drug. Iontophoresis stimulated skin drug permeation compared to the passive control. However, the antioxidant presence reduced DTIC permeation under the lower currents of 0.10 and 0.25 mA/cm2, which was compensated by increasing the current density to 0.50 mA/cm2. At 0.50 mA/cm2, iontophoresis enhanced topical cutaneous drug permeation 7-fold (p < 0.05) compared to the passive control. DTIC showed a concentration-dependent antiproliferative effect on melanoma cell lines. Thus, iontophoresis intensifies DTIC skin penetration in concentrations that can reduce cell viability and induce cell death. In conclusion, DTIC cutaneous delivery mediated by iontophoresis is a promising approach for treating melanomas and other skin tumors.

Interactions of human serum albumin with phosphate and Tris buffers: impact on paclitaxel binding and nanoparticles self-assembly.

AIM: To investigate the conformational changes in human serum albumin (HSA) caused by chemical (CD) and thermal denaturation (TD) at pH 7.4 and 9.9, crucial for designing controlled drug delivery systems with paclitaxel (PTX). METHODS: Experimental and computational methods, including differential scanning calorimetry (DSC), UV-Vis and intrinsic fluorescence spectroscopy, mean diameter, polydispersity index (PDI), ζ-potential, encapsulation efficiency (EE), in vitro release and protein docking studies were conducted to study the HSA denaturation and nanoparticles (NPs) preparation. RESULTS: TD at pH 7.4 produced smaller NPs (287.1 ± 12.9 nm) than CD at pH 7.4 with NPs (584.2 ± 47.7 nm). TD at pH 9.9 exhibited high EE (97.3 ± 0.2%w/w) with rapid PTX release (50% within 1h), whereas at pH 7.4 (96.4 ± 2.1%w/w), release only 40%. ζ-potentials were around -30 mV. CONCLUSION: Buffer type and pH significantly influence NP properties. TD in PBS at pH 7.4, provided optimal conditions for a stable and efficient drug delivery system.

Development of inhaled moxifloxacin-metformin formulation as an alternative for pulmonary tuberculosis treatment.

Resistant M. tuberculosis strains threaten pulmonary tuberculosis (P-TB) control since they limit drug options. Drug repositioning and new development strategies are urgently required to overcome resistance. Studies have already shown the beneficial role of the oral antidiabetic metformin as an anti-tuberculosis adjuvant drug. This work aimed to develop an inhalatory dry powder co-formulation of metformin and moxifloxacin to figure out a future option for P-TB treatment. Pre-formulation evaluations indicated the physicochemical compatibility of constituents, demonstrating powder crystallinity and acceptable drug content. Eight moxifloxacin-metformin dry powder formulations were produced by spray drying, and solid-state characterizations showed partial amorphization, ascribed to moxifloxacin. Four formulations containing L-leucine exhibited micromeritic and in vitro deposition profiles indicating pulmonary delivery suitability, like spherical and corrugated particle surface, geometric diameters < 5 µm, high emitted doses (>85 %), and mass median aerodynamic diameters between 1-5 µm. The use of a second spray dryer model further optimized the aerodynamic properties and yield of the best formulation, demonstrating the influence of the equipment used on the product obtained. Moreover, the final formulation showed high in vitro cell tolerability and characteristics in permeability studies indicative of good drug retention in the lungs.

Self-perception of Genital Appearance following a Vaginal Delivery, C-section and Nulliparous Women in a Hispanic Population in Puerto Rico.

OBJECTIVE: Childbirth is considered to be both beautiful and traumatic. Following a vaginal delivery, some women express discontent with the appearance of their genitalia on social media and/or websites. This study explored how some women perceived their genitalia, post childbirth. Three groups were compared: women with a vaginal delivery, those with a cesarean-section, and those who had never given birth. METHODS: After the study received approval from the institutional review board, 224 female participants living in Puerto Rico and aged 21 to 42 years completed a questionnaire about their genital self-image. RESULTS: Approximately 51% (n = 115) of the participants had never given birth; the others had given birth via C-section 23% (n = 51) or vaginally 26% (n = 58). In all 3 groups, 84% felt positive about their genitals, 79% expressed their satisfaction with the appearance of their genitals and 84%, with their size; 81% were not ashamed of their genitals. CONCLUSION: Logistic regression found no significant difference in genital self-perception between delivery groups or nulliparous women. The adjusted odds ratios for positive genital image varied slightly between delivery methods but were not statistically significant (ranging from 0.65 to 1.11 for vaginal deliveries, and 0.42 to 1.00 for C-sections; P > .05). This suggests that the method of delivery does not have a significant impact on women's genital self-perception. However, for the 21% with negative perceptions, targeted support is essential; for those struggling with their self-image after childbirth, our results can inform support services to address concerns.

Association of birth and periodontal disease in Bolivia, Chile and Colombia / Asociación de parto prematuro y enfermedad periodontal en Bolivia, Chile y Colombia.

Introducción. El parto prematuro es un problema médico, social y económico importante, causa gran mortalidad y morbilidad neonatal, tiene un impacto importante en el sistema de salud y afecta la calidad de vida de las familias. El peso de los recién nacidos de madres con enfermedad periodontal es significativamente menor en comparación con los de madres no afectadas por esta enfermedad bucal. Este resultado adverso se considera un problema de salud pública global según los datos epidemiológicos. Objetivo. Determinar la asociación entre la prevalencia de parto prematuro y la enfermedad periodontal en Bolivia, Chile y Colombia entre el 2000 y el 2020. Materiales y métodos. Este estudio ecológico consideró las poblaciones de mujeres de Bolivia, Chile y Colombia, y la prevalencia de partos prematuros y enfermedad periodontal, discriminadas por grupos de edad. El estudio abarcó el período entre el 2000 y el 2020. La estrategia de búsqueda con la herramienta de investigación del Institute for Health Metrics and Evaluation incluyó prevalencia, grupos de edad, años entre 2000 y 2020, causas de parto prematuro y enfermedad periodontal, contexto y ubicaciones, mujeres y tasas. El análisis estadístico incluyó una regresión lineal simple entre parto prematuro y enfermedad periodontal para cada grupo de edad dentro de cada país. Resultados. Las tasas de partos prematuros fueron mayores en el grupo de 15 a 19 años (Bolivia: 697.563, Chile: 844.864, Colombia: 804.126). La prevalencia de la enfermedad periodontal aumentó con la edad, particularmente en el grupo de 45 a 49 años (Bolivia: 22'077.854, Chile: 34'297.901, Colombia: 32'032,830). Según los grupos de edad, la regresión lineal fue estadísticamente significativa (p < 0,001) para todos los grupos evaluados de la población boliviana, en los grupos mayores de 30 años para las colombianas y solo en el grupo de 15 a 19 años para las mujeres chilenas. Conclusión. Se encontró asociación entre el parto prematuro y la enfermedad periodontal en todos los grupos de edad en Bolivia, solo en el grupo de 15 a 19 años en Chile, y de 30 años y más en Colombia en el período evaluado de 20 años.

Introducción. El parto prematuro es un problema médico, social y económico importante, causa gran mortalidad y morbilidad neonatal, tiene un impacto importante en el sistema de salud y afecta la calidad de vida de las familias. El peso de los recién nacidos de madres con enfermedad periodontal es significativamente menor en comparación con los de madres no afectadas por esta enfermedad bucal. Este resultado adverso se considera un problema de salud pública global según los datos epidemiológicos. Objetivo. Determinar la asociación entre la prevalencia de parto prematuro y la enfermedad periodontal en Bolivia, Chile y Colombia entre el 2000 y el 2020. Materiales y métodos. Este estudio ecológico consideró las poblaciones de mujeres de Bolivia, Chile y Colombia, y la prevalencia de partos prematuros y enfermedad periodontal, discriminadas por grupos de edad. El estudio abarcó el período entre el 2000 y el 2020. La estrategia de búsqueda con la herramienta de investigación del Institute for Health Metrics and Evaluation incluyó prevalencia, grupos de edad, años entre 2000 y 2020, causas de parto prematuro y enfermedad periodontal, contexto y ubicaciones, mujeres y tasas. El análisis estadístico incluyó una regresión lineal simple entre parto prematuro y enfermedad periodontal para cada grupo de edad dentro de cada país. Resultados. Las tasas de partos prematuros fueron mayores en el grupo de 15 a 19 años (Bolivia: 697.563, Chile: 844.864, Colombia: 804.126). La prevalencia de la enfermedad periodontal aumentó con la edad, particularmente en el grupo de 45 a 49 años (Bolivia: 22'077.854, Chile: 34'297.901, Colombia: 32'032,830). Según los grupos de edad, la regresión lineal fue estadísticamente significativa (p < 0,001) para todos los grupos evaluados de la población boliviana, en los grupos mayores de 30 años para las colombianas y solo en el grupo de 15 a 19 años para las mujeres chilenas. Conclusión. Se encontró asociación entre el parto prematuro y la enfermedad periodontal en todos los grupos de edad en Bolivia, solo en el grupo de 15 a 19 años en Chile, y de 30 años y más en Colombia en el período evaluado de 20 años.

Genetic association study of preterm birth and gestational age in a population-based case-control study in Peru.

BACKGROUND: Preterm birth (PTB) affects ∼15 million pregnancies worldwide. Genetic studies have identified several candidate loci for PTB, but results remain inconclusive and limited to European populations. Thus, we conducted a genome-wide association study (GWAS) of PTB and gestational age at delivery (GA) among 2,212 Peruvian women. METHODS: PTB cases delivered≥20 weeks' but < 37 weeks' gestation, while controls delivered at term (≥37 weeks but <42 weeks). Multivariable regressions were used to identify genetic markers for PTB and GA (∼6 million SNPs), adjusting for maternal age and the first two genetic principal components. In silico functional analysis was conducted among top signals detected with an arbitrary P < 1.0×10-5 . We sought to replicate genetic markers for PTB and GA identified in Europeans, and we developed a genetic risk score for GA based on European markers. RESULTS: Mean GA was 30 ± 4 weeks in PTB cases (N = 933) and 39 ± 1 in the controls (N = 1,279). No associatiosn were identified at genome-wide level. Nominal PTB variants were enriched for biological pathways associated with polyketide, progesterone, steroid hormones, and glycosyl metabolism. Nominal GA variants were enriched in intronic regions and cancer pathways. Variants in WNT4 associated with GA in Europeans were replicated in our study. A genetic risk score was associated with a 2-day longer GA (P = 0.002) in our sample. CONCLUSIONS: This study identified various signals suggestively associated with PTB and GA in pregnant Peruvian women. None of these variants overlapped with signals previously identified in Europeans.

Bcl-2 knockdown by multifunctional lipid nanoparticle and its influence in apoptosis pathway regarding cutaneous melanoma: in vitro and ex vivo studies.

Multifunctional therapies have emerged as innovative strategies in cancer treatment. In this research article, we proposed a nanostructured lipid carrier (NLC) designed for the topical treatment of cutaneous melanoma, which simultaneously delivers 5-FU and Bcl-2 siRNA. The characterized nanoparticles exhibited a diameter of 259 ± 9 nm and a polydispersion index of 0.2, indicating a uniform size distribution. The NLCs were primarily localized in the epidermis, effectively minimizing the systemic release of 5-FU across skin layers. The ex vivo skin model revealed the formation of a protective lipid film, decreasing the desquamation process of the stratum corneum which can be associated to an effect of increasing permeation. In vitro assays demonstrated that A375 melanoma cells exhibited a higher sensitivity to the treatment compared to non-cancerous cells, reflecting the expected difference in their metabolic rates. The uptake of NLC by A375 cells reached approximately 90% within 4 h. The efficacy of Bcl-2 knockdown was thoroughly assessed using ELISA, Western blot, and qRT-PCR analyses, revealing a significant knockdown and synergistic action of the NLC formulation containing 5-FU and Bcl-2 siRNA (at low concentration --100 pM). Notably, the silencing of Bcl-2 mRNA also impacted other members of the Bcl-2 protein family, including Mcl-1, Bcl-xl, BAX, and BAK. The observed modulation of these proteins strongly indicated the activation of the apoptosis pathway, suggesting a successful inhibition of melanoma growth and prevention of its in vitro spread.

Electronic cigarettes: "wolves in sheep's clothing".

OBJECTIVE: To provide cutting-edge information on the impact and risks of using Electronic Nicotine Delivery Systems (ENDS) by children and adolescents, based on the latest evidence published in the literature. DATA SOURCE: A comprehensive search was carried out on PubMed, using the expressions ''electronic cigarettes'' OR ''electronic nicotine delivery systems" OR "vaping" AND ''adolescent'' AND "risks" AND ''acute lung injury'. All retrieved articles had their titles and abstracts read to identify and fully read the papers reporting the most recent evidence on each subject. SUMMARY OF FINDINGS: The use of ENDS has alarmingly increased in Brazil and around the world. The possibility of customizing use, the choice of flavors and nicotine content, and the general notion that these devices are harmless when compared to conventional cigarettes are some of the factors responsible for this increase. Numerous scientific studies have proven that electronic cigarettes have serious consequences for the respiratory system, such as EVALI (E-cigarette or Vaping-Associated Lung Injury) and difficult-to-control asthma, as well as harmful effects on the neurological, cardiovascular, gastrointestinal, and immunological systems. High concentrations of nicotine make many young people addicted to this substance. In Brazil, commercialization, import, and advertising are prohibited. The viable interventions to address the use of these devices in children and adolescents are prevention and behavioral counseling. CONCLUSION: There is clear scientific evidence that these devices pose a risk to the physical and mental health of children and adolescents.

Continuity of care during severe civil unrest with a model of community-based HIV care: a retrospective cohort study from Haiti.

Background: There are limited data on the effectiveness of differentiated service delivery (DSD) for HIV care during sociopolitical turmoil. We assessed outcomes with a DSD model of care that includes patient choice between community-based antiretroviral therapy (ART) centres, home-based ART dispensing, or facility-based care at GHESKIO clinic during a period of severe civil unrest in Port-au-Prince, Haiti. Methods: This retrospective analysis included data on patients with at least one HIV visit at GHESKIO between May 1, 2019, and December 31, 2021. Multivariable logistic regression models were used to assess predictors of attending ≥1 community visit during the study period, and failure to attend timely visits. HIV-1 RNA test results were reported among patients who had been ART for ≥3 months at last visit. Findings: Of the 18,625 patients included in the analysis, 9659 (51.9%) attended at least one community visit. The proportion of community visits ranged from 0.3% (2019) to 44.1% (2021). Predictors of ≥1 community visit included male sex (aOR: 1.13; 95% CI: 1.06, 1.20), secondary education (aOR: 1.07; 95% CI: 1.01, 1.14), income > $USD 1.00/day (aOR: 1.24; 95% CI: 1.14, 1.35), longer duration on ART (aOR: 1.08 per additional year; 95% CI: 1.07, 1.09), and residence in Carrefour/Gressier (p < 0.0001 in comparisons with all other zones). Younger age and shorter time on ART were associated with late visits and loss to follow-up. Among 12,586 patients with an on-time final visit who had been on ART for ≥3 months, 11,131 (88.4%) received a viral load test and 9639 (86.6%) had HIV-1 RNA < 1000 copies/mL. Interpretation: The socio-political situation in Haiti has presented extraordinary challenges to the health care system, but retention and viral suppression rates remain high with a model of community-based HIV care. Additional interventions are needed to improve outcomes for younger patients, and those with shorter time on ART. Funding: No funding.

Advances, limitations and perspectives in the use of celecoxib-loaded nanocarriers in therapeutics of cancer.

Cancer is highlighted as a major global health challenge in the XXI century. The cyclooxygenase-2 (COX-2) enzyme rises as a widespread tumor progression marker. Celecoxib (CXB) is a selective COX-2 inhibitor used in adjuvant cancer therapy, but high concentrations are required in humans. In this sense, the development of nanocarriers has been proposed once they can improve the biopharmaceutical, pharmacokinetic and pharmacological properties of drugs. In this context, this article reviews the progress in the development of CXB-loaded nanocarriers over the past decade and their prospects. Recent advances in the field of CXB-loaded nanocarriers demonstrate the use of complex formulations and the increasing importance of in vivo studies. The types of CXB-loaded nanocarriers that have been developed are heterogeneous and based on polymers and lipids together or separately. It was found that the work on CXB-loaded nanocarriers is carried out using established techniques and raw materials, such as poly (lactic-co-glicolic acid), cholesterol, phospholipids and poly(ethyleneglycol). The main improvements that have been achieved are the use of cell surface ligands, the simultaneous delivery of different synergistic agents, and the presence of materials that can provide imaging properties and other advanced features. The combination of CXB with other anti-inflammatory drugs and/or apoptosis inducers appears to hold effective pharmacological promise. The greatest advance to date from a clinical perspective is the ability of CXB to enhance the cytotoxic effects of established chemotherapeutic agents.

Analyzing innovative policies and practices for palliative care in Portugal: a qualitative study.

BACKGROUND: Countries with formal policies for palliative care, and advanced and integrated practices in this field, such as Portugal, face challenges in achieving excellence in care, particularly in home-based assistance. Issues include care coordination among providers, confusion regarding the roles of each health care professional in the network, and a lack of monitoring and evaluation of actions. Our objective was to analyze the implementation of palliative care in primary health care in Portugal. METHODS: We conducted a qualitative, descriptive, and exploratory study in Portugal involving health care professionals with experience in palliative care. The data were collected through semistructured interviews and focus groups between March and October 2023. Eighteen health care professionals participated. We used the Alceste software for lexicographic analysis. The research was authorized by an Ethics Committee. RESULTS: Four classes were identified; classes 1 and 2, comprising 77% of the corpus, addressed the study objectives. Participants highlighted inequitable access, strategic development plans with unattainable short-term goals; and low literacy. They emphasized the importance of legislation, professional training initiatives for generalist palliative care at home, and early referral. Home-based challenges included professionals' lack of exclusive dedication, absence of 24/7 coverage, and unavailability of capable family caregivers. The networks' response to hospital admissions and patient transitions from hospital to home, with access to the specialized team, was also inadequate. CONCLUSIONS: Health care professionals aim to increase patients' time spent at home, reduce emergency department visits, and minimize hospitalizations by leveraging the resources of the national palliative care network. In addition to investments to sustain network implementation and legally guaranteed palliative care rights, the country must focus on measurable indicators for evaluating and monitoring actions, providing better guidance in the short, medium, and long term.

Chondroitin Sulfate for Cartilage Regeneration, Administered Topically Using a Nanostructured Formulation.

In the pharmaceutical sector, solid lipid nanoparticles (SLN) are vital for drug delivery incorporating a lipid core. Chondroitin sulfate (CHON) is crucial for cartilage health. It is often used in osteoarthritis (OA) treatment. Due to conflicting results from clinical trials on CHON's efficacy in OA treatment, there has been a shift toward exploring effective topical systems utilizing nanotechnology. This study aimed to optimize a solid lipid nanoparticle formulation aiming to enhance CHON permeation for OA therapy. A 3 × 3 × 2 Design of these experiments determined the ideal parameters: a CHON concentration of 0.4 mg/mL, operating at 20,000 rpm speed, and processing for 10 min for SLN production. Transmission electron microscopy analysis confirmed the nanoparticles' spherical morphology, ensuring crucial uniformity for efficient drug delivery. Cell viability assessments showed no significant cytotoxicity within the tested parameters, indicating a safe profile for potential clinical application. The cell internalization assay indicates successful internalization at 1.5 h and 24 h post-treatment. Biopharmaceutical studies supported SLNs, indicating them to be effective CHON carriers through the skin, showcasing improved skin permeation and CHON retention compared to conventional methods. In summary, this study successfully optimized SLN formulation for efficient CHON transport through pig ear skin with no cellular toxicity, highlighting SLNs' potential as promising carriers to enhance CHON delivery in OA treatment and advance nanotechnology-based therapeutic strategies in pharmaceutical formulations.