12th Tuscany Retreat on Cancer Research and Apoptosis: Genetic profiling, resistance mechanisms and novel treatment concepts in cancer and neurodegeneration.

The 12th Tuscany Retreat on Cancer Research and Apoptosis was held on August 19-26, 2023. The biennial retreat aims to bring together scientists who advance research in cancer, cell death, and neurodegenerative diseases. Topics covered ranged from drug resistance in cancer to insights into novel molecular cell signaling mechanisms and targets, all related to the pathways and molecules that regulate programmed cell death and the diseases that result from the dysregulation of programmed cell death. In this meeting review, we summarize the content of the most recent retreat.

Establishment of a Latin American dataset to enable the construction of gestational weight gain charts for adolescents.

Gestational weight gain is an important indicator for monitoring nutritional status during pregnancy. However, there are no gestational weight gain references created for adolescents or national datasets to enable the construction of such graphs up to date. This manuscript aims to describe the creation of a Latin American dataset to construct gestational weight gain references for adolescents aged 10-19 years old. Gestational weight gain data from studies conducted in nine countries (Argentina, Brazil, Chile, Colombia, Mexico, Panama, Paraguay, Peru, and Uruguay) collected between 2003 and 2021 were harmonized. Data on height, weight, and gestational age in at least two gestational trimesters were included. Pregnant adolescents should be free of diseases that could affect weight, and newborns should weigh between 2,500-4,000 g and be free of congenital malformations. The final dataset included 6,414 individuals after data cleaning. Heterogeneity between the countries was assessed by calculating standardized site differences for GWG and z scores of height-for-age. Several imputation procedures were tested, and approximately 10% of the first-trimester weights were imputed. The prevalence of individuals with underweight (1.5%) and obesity (5.3%) was low, which may lead to problems when modeling the curves for such BMI categories. Maternal height and gestational weight gain did not show significant differences by country, according to the standardized site differences. A harmonized dataset of nine countries with imputed data in the first trimester of pregnancy was prepared to construct Latin American gestational weight gain curves for adolescents.

Neumonía de organización como causa de hipoxemia persistente a la tercera semana de infección por SARS-CoV-2. Reporte de caso / Organization pneumonia as a cause of persistent hypoxemia in the third week of SARS CoV-2 infection, case report

El Coronavirus 2 es un betacoronavirus de ARN responsable de la enfermedad por coronavirus 2019 (COVID-19). Fue detectado por primera vez en Wuhan, China y se propagó rápidamente a nivel mundial, llevando a la OMS a declarar una pandemia en marzo de 2020. Para julio de 2021, se habían registrado casi 196 millones de casos confirmados de COVID-19, siendo responsable de más de cuatro millones de muertes en todo el mundo. En la mayoría de los casos, los pacientes presentan síntomas respiratorios que van desde leves hasta graves, pudiendo desencadenar lesiones pulmonares agudas y disfunción multiorgánica; incluso se han reportado casos de hipoxemia refractaria, lo que implica una elevada morbimortalidad. Las posibles causas incluyen infecciones secundarias, enfermedad tromboembólica pulmonar, fibrosis pulmonar y reinfección por SARS-CoV-2. En pacientes con COVID-19 se ha observado la neumonía de organización como una complicación en la fase subaguda y tardía de la enfermedad, desencadenando un deterioro clínico y radiológico significativo. El tratamiento con glucocorticoides ha mostrado una respuesta favorable en estos casos. Presentamos un caso de neumonía de organización relacionado con la infección por SARS-CoV-2 que, aunque no contó con confirmación histológica, la integración de la presentación clínica, la evolución y los hallazgos radiológicos permitieron realizar la aproximación diagnóstica, destacando la importancia del manejo adecuado con glucocorticoides en estos casos. Sin embargo, se necesitan más estudios para evaluar el desarrollo de esta complicación en una población más amplia.

Coronavirus 2 is an RNA beta coronavirus responsible for coronavirus disease 2019 (COVID-19). It was first detected in Wuhan, China, and spread rapidly globally, leading the WHO to declare a pandemic in March 2020. By July 2021, there had been nearly 196 million confirmed cases, being responsible for more than four million deaths worldwide. In most cases, patients present with respiratory symptoms ranging from mild to severe, which can lead to acute lung lesions and multi-organ dysfunction; cases of refractory hypoxemia have even been reported, which implies high morbidity and mortality. Possible causes include secondary infections, pulmonary thromboembolic disease, pulmonary fibrosis, and SARS-CoV-2 reinfection. Most COVID-19 patients exhibit respiratory symptoms, ranging from mild to severe, with the potential for acute lung injuries and multiorgan dysfunction leading to high mortality. Cases of refractory hypoxemia in COVID-19 patients have been reported, indicating significant morbidity and mortality. Possible causes include secondary infections, pulmonary thromboembolism, pulmonary fibrosis, and reinfection by SARS-CoV-2. In patients with COVID-19, organization pneumonia has been observed as a complication in the subacute and late phase of the disease, triggering significant clinical and radiological deterioration. Treatment with glucocorticoids has shown a favorable response in these cases. We present a case of organizing pneumonia in relation SARS-CoV-2 infection that, although it did not have histological confirmation, the clinical presentation, evolution and radiological findings allowed a diagnostic approach, highlighting the importance of proper management with glucocorticoids in these cases. However, more studies are needed to evaluate the development of this complication in a larger population.

Gestational weight gain charts for Latin American adolescents.

Monitoring gestational weight gain (GWG) throughout pregnancy among adolescents is important for detecting individuals at risk and timely intervention. However, there are no specific tools or guidelines for GWG monitoring of this group. We aimed to construct GWG charts for pregnant adolescents (10-19 years old) according to pre-pregnancy body mass index (BMI) using a pooled dataset from nine Latin American countries. Datasets from Argentina, Brazil, Chile, Colombia, Mexico, Panama, Paraguay, Peru, and Uruguay collected between 2003 and 2021 were combined after data cleaning and harmonization. Adolescents free of diseases that could affect GWG and who gave birth to newborns weighing between 2,500-4,000 g and free of congenital malformations were included. Multiple imputation techniques were applied to increase the sample size available for underweight and obesity categories. Generalized Additive Models for Location, Scale, and Shape were used to construct the charts of GWG according to gestational age. Internal and external validation procedures were performed to ensure that models were not over-adjusted to the data. The cohort included 6,414 individuals and 29,414 measurements to construct the charts and 1,684 individuals and 8,879 measurements for external validation. The medians (and interquartile ranges) for GWG at 40 weeks according to pre-pregnancy BMI were: underweight, 14.9 (11.9-18.6); normal weight, 14.0 (10.6-17.7); overweight, 11.6 (7.7-15.6); obesity, 10.6 kg (6.7-14.3). Internal and external validation showed that the percentages above/below selected percentiles were close to those expected, except for underweight adolescents. These charts describe the GWG throughout pregnancy among Latin American adolescents and represent a significant contribution to the prenatal care of this group. GWG cut-offs based on values associated with lower risks of unfavorable outcomes for the mother-child binomial should be determined before implementing the charts in clinical practice.

Efficacy of Apremilast Gels in Mouse Model of Imiquimod-Induced Psoriasis Skin Inflammation.

Apremilast (APM) is a novel drug for the treatment of psoriasis and psoriatic arthritis. APM is a phosphodiesterase 4 (PDE4) inhibitor, raising intracellular cAMP levels and thereby decreasing the inflammatory response by modulating the expression of TNF-α, IL-17, IL-23, and other inflammatory cytokines. The goal of this study is to develop APM gels as a new pharmaceutical formulation for the treatment of topical psoriasis. APM was solubilized in Transcutol-P and incorporated into Pluronic F127, Sepigel, and carbomer bases at different proportions. All formulations were characterized physiochemically. A biopharmaceutical study (release profile) was performed, and ex vivo permeation was evaluated using a human skin model. A toxicity assay was carried out on the HaCaT cell line. A mouse model of imiquimod-induced psoriasis skin inflammation was carried out to determine its efficacy by histological analysis, RNA extraction, and RT-qPCR assays. APM gel formulations showed good physicochemical characteristics and a sustained release profile. There was no permeation of any gel measured through human skin, indicating a high retained amount of APM on the skin. Cell viability was greater than 80% at most dilution concentrations. APM gels treated the psoriasis mouse model, and it shows a reduction in the proinflammatory cytokines (IL-8, IL-17A, IL-17F, and IL-23). APM gels could be a new approach for the treatment of topical psoriasis.

Therapeutic Applications of Essential Oils from Native and Cultivated Ecuadorian Plants: Cutaneous Candidiasis and Dermal Anti-Inflammatory Activity.

Essential oils are a complex mixture of aromatic substances whose pharmacological actions, including antimicrobial, antioxidant, anticancer, and anti-inflammatory activities, have been widely reported. This study aimed to evaluate the anti-Candida and dermal anti-inflammatory activity of essential oils from native and cultivated Ecuadorian plants. Essential oils from Bursera graveolens, Dacryodes peruviana, Mespilodaphne quixos, and Melaleuca armillaris were isolated by hydrodistillation and were characterized physically and chemically. Its tolerance was analyzed by in vitro and in vivo studies. The antifungal activity was studied against Candida albicans, Candida glabrata, and Candida parapsilosis, whereas the anti-inflammatory effect was evaluated by a mouse ear edema model. The main compounds were limonene, α-phellandrene, (E)-methyl cinnamate, and 1,8-cineole, respectively. All essential oils showed high tolerability for skin application, antifungal activity against the three Candida strains, and anti-inflammatory efficacy by decreasing edema and overexpression of pro-inflammatory cytokines. Dacryodes peruviana essential oil showed the highest antifungal activity. On the other hand, Dacryodes peruviana and Melaleuca armillaris showed the greatest anti-inflammatory potential, decreasing edema by 53.3% and 65.25%, respectively, and inhibiting the overexpression of TNF-α, IL-8, IL-17A, and IL-23. The results suggest that these essential oils could be used as alternative therapies in the treatment of both cutaneous candidiasis and dermal inflammation.

Understanding the Role of Human Papillomavirus in Head and Neck Cancer of Unknown Primary: A Systematic Review.

This systematic review aims to provide a comprehensive understanding of the role of human papillomavirus (HPV) in head and neck cancer of unknown primary (HNCUP). HNCUP is a rare type of cancer with an unknown primary site, which makes it difficult to diagnose and treat. The review includes articles published between 2013 and 2023 that investigated the prevalence of HPV in HNCUP, its association with clinical outcomes, and its potential implications for diagnosis and treatment. The search was conducted in 11 electronic databases, and the gray literature: Cochrane, Cumed, IBECS, JAMA Network, LILACS, MEDLINE Ovid, MEDLINE-EBSCO, PubMed, Scopus, SciELO, and Taylor & Francis Online; a total of 23 studies met the inclusion criteria. The review found that HPV is present in a significant proportion of HNCUP cases, ranging from 15.5% to 100%. HNCUP incidence is increasing, and the presence of HPV was associated with improved clinical outcomes in some studies, such as overall survival and disease-free survival; but was found to have no association with outcomes in others. This may have implications for diagnostic and treatment strategies. The findings of this review suggest that further research is needed to better understand the role of HPV in HNCUP and to develop targeted therapies for this disease.

Semi-Solid Dosage Forms Containing Pranoprofen-Loaded NLC as Topical Therapy for Local Inflammation: In Vitro, Ex Vivo and In Vivo Evaluation.

Pranoprofen (PRA)-loaded nanostructured lipid carriers (NLC) have been dispersed into blank gels composed of 1% of Carbomer 940 (PRA-NLC-Car) and 3% of Sepigel® 305 (PRA-NLC-Sep) as a novel strategy to refine the biopharmaceutical profile of PRA, for dermal administration in the treatment of skin inflammation that may be caused by possible skin abrasion. This stratagem intends to improve the joining of PRA with the skin, improving its retention and anti-inflammatory effect. Gels were evaluated for various parameters such as pH, morphology, rheology, and swelling. In vitro drug release research and ex vivo permeation through the skin were carried out on Franz diffusion cells. Additionally, in vivo assays were carried out to evaluate the anti-inflammatory effect, and tolerance studies were performed in humans by evaluating the biomechanical properties. Results showed a rheological profile common of semi-solid pharmaceutical forms for dermal application, with sustained release up to 24 h. In vivo studies using PRA-NLC-Car and PRA-NLC-Sep in Mus musculus mice and hairless rats histologically demonstrated their efficacy in an inflammatory animal model study. No signs of skin irritation or modifications of the skin's biophysical properties were identified and the gels were well tolerated. The results obtained from this investigation concluded that the developed semi-solid formulations represent a fitting drug delivery carrier for PRA's transdermal delivery, enhancing its dermal retention and suggesting that they can be utilized as an interesting and effective topical treatment for local skin inflammation caused by a possible abrasion.

Importancia del conocimiento anatómico del espacio extraperitoneal y su utilidad en los abordajes quirúrgicos / Importance of anatomical knowledge of the extraperitoneal space and its usefulness in surgical approaches

Introducción. El espacio extraperitoneal, se define como el segmento topográfico ubicado entre el peritoneo parietal internamente y la fascia transversalis externamente. Como resultado del desarrollo y consolidación de la cirugía laparoscópica, en particular de la herniorrafia inguinal por esta vía, se ha presentado un renovado y creciente interés en esta área anatómica, debido a la importancia de su conocimiento detallado en la cirugía de mínima invasión. Métodos. Se hizo una revisión narrativa de la literatura para presentar una información actualizada y detallada sobre la anatomía del espacio extraperitoneal y su importancia en diferentes procedimientos quirúrgicos realizados actualmente. Resultados. Por fuera del espacio peritoneal, se encuentran las áreas anatómicas externas al peritoneo parietal, que incluyen la preperitoneal y la retroperitoneal. Mediante la laparoscopia, se pueden localizar en estos espacios cinco triángulos anatómicos, además de la corona mortis y el triángulo supra vesical. Conclusión. El conocimiento del espacio extraperitoneal es de gran importancia para el cirujano general, teniendo en cuenta los múltiples procedimientos que requieren el abordaje de esta área topográfica

Introduction. The extraperitoneal space is defined as the topographic segment located between the parietal peritoneum internally and the fascia transversalis externally. As a result of the development and consolidation of laparoscopic surgery, particularly inguinal herniorrhaphy by this route, there has been a renewed and growing interest in this anatomical area, due to the importance of its detailed knowledge in minimally invasive surgery. Methods. A narrative review of the literature was made to present updated and detailed information on the anatomy of the extraperitoneal space and its importance in different surgical procedures currently performed. Results. Outside the peritoneal space are the anatomical areas external to the parietal peritoneum, including the preperitoneal and extraperitoneal. Using laparoscopy, five anatomical triangles, in addition to the corona mortis and the supravesical triangle, can be located in these spaces. Conclusion. Knowledge of the extraperitoneal space is of great importance for the general surgeon, taking into account the multiple procedures that require the approach of this topographic area

Validation and Psychometric Properties of the Tobacco Urge Management Scale (TUMS).

BACKGROUND: During quit attempts, smokers must overcome smoking urges triggered by environmental cues and nicotine withdrawal symptoms. This study investigates the psychometric properties of the 12-item Tobacco Urge Management Scale (TUMS), a new measure of smoking urge management behaviors. METHODS: We analyzed secondary data (n = 327) from a behavioral smoking cessation intervention trial, Kids Safe and Smokefree (KiSS). RESULTS: Confirmatory factor analysis of the TUMS indicated that a one-factor model and a correlated two-factor model had similar model fit indices, and a Chi-square difference test supported the one-factor model. Further study of the parsimonious one-factor scale provided evidence of reliability and construct validity. Known group validity was evidenced by significantly higher TUMS scores in the KiSS intervention arm receiving urge management skills training than in the control arm (p < 0.001). Concurrent validity was evidenced by TUMS's inverse association with cigarettes smoked per day and positive associations with nonsmoking days, 7-day abstinence, and self-efficacy to control smoking behaviors (p's < 0.05). CONCLUSION: The TUMS is a reliable, valid measure of smoking urge management behaviors. The measure can support theory-driven research on smoking-specific coping mechanisms, inform clinical practice by identifying coping strategies that might be under-utilized in treatment-seeking smokers, and function as a measure of treatment adherence in cessation trials that target urge management behaviors.

Gel Formulations with an Echinocandin for Cutaneous Candidiasis: The Influence of Azone and Transcutol on Biopharmaceutical Features.

Caspofungin is a drug that is used for fungal infections that are difficult to treat, including invasive aspergillosis and candidemia, as well as other forms of invasive candidiasis. The aim of this study was to incorporate Azone in a caspofungin gel (CPF-AZ-gel) and compare it with a promoter-free caspofungin gel (CPF-gel). An in vitro release study using a polytetrafluoroethylene membrane and ex vivo permeation into human skin was adopted. The tolerability properties were confirmed by histological analysis, and an evaluation of the biomechanical properties of the skin was undertaken. Antimicrobial efficacy was determined against Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. CPF-AZ-gel and CPF-gel, which had a homogeneous appearance, pseudoplastic behavior, and high spreadability, were obtained. The biopharmaceutical studies confirmed that caspofungin was released following a one-phase exponential association model and the CPF-AZ gel showed a higher release. The CPF-AZ gel showed higher retention of caspofungin in the skin while limiting the diffusion of the drug to the receptor fluid. Both formulations were well-tolerated in the histological sections, as well as after their topical application in the skin. These formulations inhibited the growth of C. glabrata, C. parapsilosis, and C. tropicalis, while C. albicans showed resistance. In summary, dermal treatment with caspofungin could be used as a promising therapy for cutaneous candidiasis in patients that are refractory or intolerant to conventional antifungal agents.

Caspase-8 is required for HSV-1-induced apoptosis and promotes effective viral particle release via autophagy inhibition.

Regulated cell death (RCD) plays an important role in the progression of viral replication and particle release in cells infected by herpes simplex virus-1 (HSV-1). However, the kind of RCD (apoptosis, necroptosis, others) and the resulting cytopathic effect of HSV-1 depends on the cell type and the species. In this study, we further investigated the molecular mechanisms of apoptosis induced by HSV-1. Although a role of caspase-8 has previously been suggested, we now clearly show that caspase-8 is required for HSV-1-induced apoptosis in a FADD-/death receptor-independent manner in both mouse embryo fibroblasts (MEF) and human monocytes (U937). While wild-type (wt) MEFs and U937 cells exhibited increased caspase-8 and caspase-3 activation and apoptosis after HSV-1 infection, respective caspase-8-deficient (caspase-8-/-) cells were largely impeded in any of these effects. Unexpectedly, caspase-8-/- MEF and U937 cells also showed less virus particle release associated with increased autophagy as evidenced by higher Beclin-1 and lower p62/SQSTM1 levels and increased LC3-I to LC3-II conversion. Confocal and electron microscopy revealed that HSV-1 stimulated a strong perinuclear multivesicular body response, resembling increased autophagy in caspase-8-/- cells, entrapping virions in cellular endosomes. Pharmacological inhibition of autophagy by wortmannin restored the ability of caspase-8-/- cells to release viral particles in similar amounts as in wt cells. Altogether our results support a non-canonical role of caspase-8 in both HSV-1-induced apoptosis and viral particle release through autophagic regulation.

Implantation of heat treatment Ti6al4v alloys in femoral bone of Wistar rats.

Two heat treatments were carried out at below (Ti6Al4V800) and above (Ti6Al4V1050) the beta-phase transformation temperature (TTRANSUS = 980 °C), to study the effect of microstructural changes on osseointegration. The alloys were implanted in the femurs of hind legs of Wistar rats for 15, 30, and 60 days. Histology of the femur sections obtained for the first 15 days showed inflammatory tissue surrounding the implants and tissue contraction, which prevented osseointegration in early stages. After 30 days, trabecular bone, reduction of inflammatory tissue around the implants, and osseointegration were observed in Ti6Al4V as received and Ti6Al4V1050 alloys, while osseointegration was detected for the three alloys after 60 days. These results were supported through morphometric studies based on the analysis of Bone Implant Contact (BIC), where there was a larger bone contact after 60 days for the Ti6Al4V1050 alloy; indicating that microstructural features of the Ti6Al4V alloys influence their osseointegration, with the lamellar microstructure (Ti6Al4V1050), being the most responsive. Graphical abstract.

Quality by Design of Pranoprofen Loaded Nanostructured Lipid Carriers and Their Ex Vivo Evaluation in Different Mucosae and Ocular Tissues.

Transmucosal delivery is commonly used to prevent or treat local diseases. Pranoprofen is an anti-inflammatory drug prescribed in postoperative cataract surgery, intraocular lens implantation, chorioretinopathy, uveitis, age-related macular degeneration or cystoid macular edema. Pranoprofen can also be used for acute and chronic management of osteoarthritis and rheumatoid arthritis. Quality by Design (QbD) provides a systematic approach to drug development and maps the influence of the formulation components. The aim of this work was to develop and optimize a nanostructured lipid carrier by means of the QbD and factorial design suitable for the topical management of inflammatory processes on mucosal tissues. To this end, the nanoparticles loading pranoprofen were prepared by a high-pressure homogenization technique with Tween 80 as stabilizer and Lanette® 18 as the solid lipid. From, the factorial design results, the PF-NLCs-N6 formulation showed the most suitable characteristics, which was selected for further studies. The permeability capacity of pranoprofen loaded in the lipid-based nanoparticles was evaluated by ex vivo transmucosal permeation tests, including buccal, sublingual, nasal, vaginal, corneal and scleral mucosae. The results revealed high permeation and retention of pranoprofen in all the tissues tested. According to the predicted plasma concentration at the steady-state, no systemic effects would be expected, any neither were any signs of ocular irritancy observed from the optimized formulation when tested by the HET-CAM technique. Hence, the optimized formulation (PF-NLCs-N6) may offer a safe and attractive nanotechnological tool in topical treatment of local inflammation on mucosal diseases.

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study.

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P = .001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P = .693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P = .001), lower time from booster (P = .043) and past breakthrough SARS-CoV-2 infection (P < .001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infection.

Three-dimensional ankle, subtalar, and hindfoot alignment of the normal, weightbearing hindfoot, in bilateral posture.

The first goal of this study was to develop reliable three-dimensional definitions of alignment for the ankle, subtalar, and hindfoot joints. These alignments are based on three-dimensional morphological features derived from renderings of the bones obtained from weightbearing computer tomography. The second goal was to establish a database quantifying the alignment of the ankle, subtalar, and hindfoot joints in a healthy population during weightbearing bilateral standing. This level 1 study was performed on 95 normal subjects in which random subjects were recruited into a control group. Weightbearing computed tomography scans of the leg were collected in neutral, bilateral, standing posture. In 30 of the subjects, both the left and right leg was scanned. Six alignment parameters for each joint were calculated from morphological measurements conducted on three-dimensional renderings of the bones. Intra- and intertester reliability was assessed from repeated measurements by several testers. Analysis of variance statistics of the alignment parameters showed no statistical differences due to age, gender, or foot side. Intraclass correlation coefficient analysis showed excellent inter- and intratester reliability. It was concluded that the alignment process is comprehensive and reliable. Therefore, without classification by gender or age, it may be used as a foundation for quantifying abnormal alignment associated with various ankle deformities. Clinical significance: The alignment methodology and control database may be used to diagnose ankle, subtalar, and hindfoot misalignment. It can also serve as basis for surgical planning designed to restore normal alignment in various hindfoot pathologies, such as ankle realignment in total ankle replacement.

In vitro mineral apposition analysis of two Colombian plant extracts on Amelogenesis imperfecta teeth.

OBJECTIVE: To determine if native Colombian Piper marginatum Jacq. and Ilex guayusa Loes plant extracts have a remineralizing effect on teeth with Amelogenesis imperfecta in comparison with the commercial products Clinpro-3M and Recaldent™. MATERIAL AND METHODS: An in vitro study was carried out with 128 human teeth slices (64 healthy and 64 with Amelogenesis imperfecta) on which an initial Raman spectroscopy was performed followed by Raman spectroscopies at 0, 24, 48, and 72 h to determine possible remineralization by observing mineral increase or decrease as a result of P. marginatum Jacq. and I. guayusa Loes extract application in comparison to control substance (Clinpro and Recaldent™) application. Obtained data were analyzed using a bivariate method with a t unidirectional test. Significant differences among groups were determined by an ANOVA with Dunnett post hoc tests. RESULTS: Native I. guayusa Loes and P. marginatum Jacq. Colombian plants extracts exhibited phosphate and orthophosphate mineral apposition, where P. marginatum Jacq. presented better results. CONCLUSIONS: Native Colombian I. guayusa Loes and P. marginatum Jacq plant extract might in the future be useful for dental tissue remineralization, as they induced phosphate and orthophosphate mineral apposition, main components of tooth enamel. These types of natural compounds can become an alternative to fluorine, whose ingestion is harmful to the human body.

Enhanced Transdermal Delivery of Pranoprofen Using a Thermo-Reversible Hydrogel Loaded with Lipid Nanocarriers for the Treatment of Local Inflammation.

A biocompatible topical thermo-reversible hydrogel containing Pranoprofen (PF)-loaded nanostructured lipid carriers (NLCs) was studied as an innovative strategy for the topical treatment of skin inflammatory diseases. The PF-NLCs-F127 hydrogel was characterized physiochemically and short-time stability tests were carried out over 60 days. In vitro release and ex vivo human skin permeation studies were carried out in Franz diffusion cells. In addition, a cytotoxicity assay was studied using the HaCat cell line and in vivo tolerance study was performed in humans by evaluating the biomechanical properties. The anti-inflammatory effect of the PF-NLCs-F127 was evaluated in adult male Sprague Daw-ley® rats using a model of inflammation induced by the topical application of xylol for 1 h. The developed PF-NLCs-F127 exhibited a heterogeneous structure with spherical PF-NLCs in the hydrogel. Furthermore, a thermo-reversible behaviour was determined with a gelling temperature of 32.5 °C, being close to human cutaneous temperature and thus favouring the retention of PF. Furthermore, in the ex vivo study, the amount of PF retained and detected in human skin was high and no systemic effects were observed. The hydrogel was found to be non-cytotoxic, showing cell viability of around 95%. The PF-NLCs-F127 is shown to be well tolerated and no signs of irritancy or alterations of the skin's biophysical properties were detected. The topical application of PF-NLCs-F127 hydrogel was shown to be efficient in an inflammatory animal model, preventing the loss of stratum corneum and reducing the presence of leukocyte infiltration. The results from this study confirm that the developed hydrogel is a suitable drug delivery carrier for the transdermal delivery of PF, improving its dermal retention, opening the possibility of using it as a promising candidate and safer alternative to topical treatment for local skin inflammation and indicating that it could be useful in the clinical environment.

Rural-urban differences in health-related quality of life: patterns for cancer survivors compared to other older adults.

PURPOSE: Health-related quality of life (HRQOL) among older cancer survivors can be impaired by factors such as treatment, comorbidities, and social challenges. These HRQOL impairments may be especially pronounced in rural areas, where older adults have higher cancer burden and more comorbidities and risk factors for poor health. This study aimed to assess rural-urban differences in HRQOL for older cancer survivors and controls. METHODS: Data came from Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS), which links cancer incidence from 18 U.S. population-based cancer registries to survey data for Medicare Advantage Organization enrollees (1998-2014). HRQOL measures were 8 standardized subscales and 2 global summary measures. We matched (2:1) controls to breast, colorectal, lung, and prostate cancer survivors, creating an analytic dataset of 271,640 participants (ages 65+). HRQOL measures were analyzed with linear regression models including multiplicative interaction terms (rurality by cancer status), controlling for sociodemographics, cohort, and multimorbidities. RESULTS: HRQOL scores were higher in urban than rural areas (e.g., global physical component summary score for breast cancer survivors: urban mean = 38.7, standard error [SE] = 0.08; rural mean = 37.9, SE = 0.32; p < 0.05), and were generally lower among cancer survivors compared to controls. Rural cancer survivors had particularly poor vitality (colorectal: p = 0.05), social functioning (lung: p = 0.05), role limitation-physical (prostate: p < 0.01), role limitation-emotional (prostate: p < 0.01), and global mental component summary (prostate: p = 0.02). CONCLUSION: Supportive interventions are needed to increase physical, social, and emotional HRQOL among older cancer survivors in rural areas. These interventions could target cancer-related stigma (particularly for lung and prostate cancers) and/or access to screening, treatment, and ancillary healthcare resources.

Riesgo psicosocial intralaboral y síndrome de desgaste profesional en psiquiatras de una clínica de Antioquia (Colombia) en el 2020: serie de casos / Intra-Labor Psychosocial Risk and Burnout Syndrome in Psychiatrists at a Clinic in Antioquia (Colombia) in 2020: Case Series / Risco psicossocial laboral e síndrome de Burnout em psiquiatras de uma clínica de Antioquia (Colômbia) em 2020: série de casos

Introducción: El síndrome de desgaste profesional es un conjunto de signos y síntomas ocasionado por trabajo, fatiga emocio-nal, despersonalización y disminución del sentido de logros personales: por lo cual en este artículo se describen las característi-cas demográficas, los riesgos psicosociales intralaborales, el síndrome y el impacto percibido sobre el trabajo por el COVID-19 en un grupo de psiquiatras. Métodos: Estudio descriptivo de serie de casos en trece psiquiatras incluidos por muestreo no probabilístico a conveniencia que completaron la escala de riesgo psicosocial intralaboral, la escala Maslach Burnout Inventory y una encuesta relacionada con coronavirus SARS-COV-2. Resultados: Los casos presentan una edad promedio de 35 años con predominio del sexo femenino. Para el 65,1 % de las personas encuestadas, la emoción prevalente fue angustia, temor al contagio e interferencia en el trabajo ante la situación de pandemia. El 69,2 % de los casos percibió que incrementó las actividades intralaborales, con aumento de consultas virtuales, resultados mayores a los obtenidos en estudios, donde los valores van desde el 30 % al 34,5 % en la misma dimensión. Conclusiones: La prevalencia de síndrome de desgaste profesional fue del 7,7 % en psiquiatras de una clínica de tercer nivel en Antioquia. En los trece casos reportados se encontró un riesgo muy alto, asociado con las condiciones laborales, así como con las actividades laborales ante la actual situación de pandemia por SARS-COV-2

Introduction: Burnout syndrome is a set of signs and symptoms related to wear and tear caused by work, emo-tional fatigue, depersonalization and decreased sense of personal achievement, for which demographic charac-teristics, intra-occupational psychosocial risks, burnout syndrome and the perceived impact on work by COVID-19 in a group of psychiatrists. Method: Descriptive study of a series of cases in 13 psychiatrists included by non-probabilistic convenience sam-pling, who completed the intra-occupational psychosocial risk scale, the Maslach Burnout Inventory scale and a survey related to the SARS-COV-2 coronavirus. Results: The cases have an average age of 35 years with a predominance of the female sex, 65.1% of the cases reported that the prevailing emotion was anxiety, fear of contagion and interference at work in the face of a pandemic situation. 69.2% of the cases, they perceived that intra-labor activities increased, with an increase in virtual consultations, results greater than those obtained in studies, where the values range from 30% to 34.5% in the same dimension. Conclusions: The prevalence of burnout syndrome was 7.7% in psychiatrists of a third-level clinic in Antioquia, in the thirteen reported cases a very high risk was found associated with working conditions, as well as work activities in the current pandemic situation by SARS-COV-2

Introdução: A síndrome de Burnout é um conjunto de sinais e sintomas ocasionado pelo excesso de trabalho, fadiga emocional, despersonalização e diminuição do sentido de logros pessoais: portanto, este artigo descreve as caraterísticas demográficas, os riscos psicossociais no trabalho, a síndrome e o impacto pela COVID-19 percebido no trabalho de um grupo de psiquiatras. Métodos: Estudo descritivo de série de casos em treze psiquiatras incluídos por amostragem não probabilística a conveniência que completaram a escala de risco psicossocial no trabalho, a Escala Maslach Burnout Inventory é uma pesquisa relacionada com o coronavírus SARS-COV-2. Resultados: A idade média dos casos é de 35 anos com uma predominância feminina. Para o 65,1 % das pessoas pesquisadas, a emoção predominante foi à angústia, o medo de contágio e a interferên-cia com o trabalho na situação pandêmica. O 69,2 % dos casos percebeu o incremento das atividades laborais, com um aumento das consultas virtuais, resultados superiores aos obtidos em estudos, onde os valores variam entre 30 % e 34,5 % na mesma dimensão. Conclusões: A prevalência da síndrome de Burnout foi de 7,7 % em psiquiatras de uma clinica de terceiro nível em Antioquia. Nos treze casos relatados, foi identificado um risco muito elevado, asso-ciado ás condições de trabalho bem como as atividades de trabalho na atual situação pandêmica da SARS-COV-2