Pirfenidone Reverts Global DNA Hypomethylation, Promoting DNMT1/UHRF/PCNA Coupling Complex in Experimental Hepatocarcinoma.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in the carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-Acetylaminofluorene (2-AAF). The HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, ß-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

Ultrasonographic features of nonvascular complications of hyaluronic acid fillers: a retrospective study at a reference center for dermatologic ultrasonography.

Hyaluronic acid filler injections have been associated with early, temporary, and delayed-onset complications. High-resolution ultrasound with Doppler analysis has been increasingly used to detect and identify such complications. We comprehensively describe the most common ultrasonographic findings of nonvascular complications associated with hyaluronic acid filler injections. This retrospective, cross-sectional, observational study was conducted at a reference center for dermatologic ultrasound in Bogotá, Colombia. Ultrasound reports documented the ultrasonographic findings of nonvascular complications of hyaluronic acid filler injections. Fifty-two complications were documented in a cohort of 50 patients (women, 88%). The infraorbital region was the most common site affected (23%), followed by the nasolabial region (22%). The Tyndall effect was the most common complication (25% of all), followed by changes in rheology (21%) and pseudosarcoidal (foreign body granuloma) reaction (15%). The Tyndall effect stood out for its distinctive ultrasonographic characteristics. We discuss the ultrasonographic findings and pathogenesis of other complications, including filler migration, early hypersensitivity, aseptic abscess, overcorrection, and filler material interaction. The clinical presentation of hyaluronic acid filler complications can be confusing, delaying timely diagnosis and treatment. High-resolution ultrasound with Doppler analysis is a valuable tool for avoiding unnecessary treatments and ensuring timely diagnosis and treatment.

Adherence to the Mediterranean Diet and its association with gastric cancer: health benefits from a Planeterranean perspective.

The Mediterranean Diet (MD) has garnered increasing attention for its potential protective effects against gastric cancer (GC). The MD's rich content of antioxidants, polyphenols, and other bioactive compounds contributes to its ability to modulate gene expression, inhibit tumor growth, and regulate apoptosis. Studies have shown significant reductions in inflammatory markers such as C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) among individuals adhering to the MD, suggesting its pivotal role in mitigating chronic inflammation-associated with cancer development. Furthermore, the MD's anti-angiogenic properties, particularly in components like olive oil, red wine, fish, and tomatoes, offer promising avenues for reducing GC risk by inhibiting tumor angiogenesis. Additionally, the MD's influence on intestinal microbiota composition underscores its potential in maintaining immune homeostasis and reducing systemic inflammation, factors crucial in GC prevention. Despite challenges such as variability in dietary adherence scoring systems and the need for further gender and geographical-specific studies, evidence supports the MD as a cost-effective and holistic approach to GC prevention. Emphasizing the role of nutrition in public health is a promising strategy with broad implications for global health and cancer prevention initiatives. Therefore, this review explores the multifaceted impacts of the MD on GC prevention, delving into its anti-inflammatory, anti-angiogenic, and molecular mechanisms.

High-Resolution Ultrasound of Odontogenic Cutaneous Sinus Tract: An International Multicentric Experience and a Review of the Literature.

OBJECTIVES: To investigate the role of high-resolution ultrasound (HR-US) in the initial and differential diagnosis of the Odontogenic Cutaneous Sinus Tract (OCST) in a multicentric setting. METHODS: Skin HR-US examinations of OCSTs performed between January 2019 and June 2023 at different Institutions were retrospectively reviewed. Epidemiological and clinical data (age, gender, location of the skin lesion, causative tooth, and the clinical suspicion) as well as HR-US imaging findings (morphology and length of the sinus tract, Doppler signal, and cortical bone interruption of maxilla or mandible) were collected. US examinations were performed by expert radiologists using a high-performance US scanner, employing a high-frequency linear probe (15 MHz or higher frequencies). In only one patient the HR-US exam was integrated with strain elastography (SE). RESULTS: Sixteen patients were enrolled with a median age of 37.6 years (range 16-70 years). The most frequent clinical suspicion was epidermal cyst, while OCST was suspected in only two cases. In all cases, HR-US depicted the sinus tract as a nodular, triangular or "champignon-shaped" lesion in the subcutaneous layer, which continued with a slightly tortuous band structure, up to the focally interrupted cortical bone plate. Furthermore, color Doppler evaluation showed color signals around and/or within the lesion, expression of inflammation. On SE, the sinus tract showed a hard pattern, due to fibrous and granulomatous tissue. CONCLUSIONS: HR-US, thanks to its high spatial resolution, allows the evaluation of OCST, and play a crucial diagnostic role, mainly when the clinical suspicious is different.

Parotid Mucoepidermoid Carcinoma in a Pediatric Patient: A Case Report.

Mucoepidermoid carcinomas (MECas) are malignant epithelial salivary gland neoplasms composed of a variable mixture of epidermoid and mucus-secreting cells arising from the ductal epithelium. Of all salivary gland tumors, MECas are the most common malignant lesions of the parotid gland. This case report aims to present a 14-year-old female patient with a history of progressive enlargement of a 3 cm in diameter, painless, mobile mass located at the parotid gland without facial nerve dysfunction. The lesion was exhaustively studied preoperatively, and studies were carried out. Contrast-enhanced computerized tomography (CECT) showed an increase in nodule numbers and size at the level of both the jugular and posterior cervical chains. In contrast, the gland's fine needle aspiration (FNA) showed a mucinous background. The histologic depiction established that the tumor was MECa of the parotid gland. The literature reviews on MECa encompass discussions about its prevalence, etiology, histological findings, and treatment.

Implementation of an ERAS protocol on cirrhotic patients in liver resection: a cohort study.

The development of laparoscopic liver surgery, the improvement in the perioperative care programs, and the surgical innovation have allowed liver resections on selected cirrhotic patients. However, the great majority of ERAS studies for liver surgery have been conducted on patients with normal liver parenchyma, while its application on cirrhotic patients is limited. The purpose of this study was to evaluate the implementation of an ERAS protocol in cirrhotic patients who underwent liver surgery. We present an analytical observational prospective cohort study, which included all adult patients who underwent a liver resection between December 2017 and December 2019 with an ERAS program. We compare the outcomes in patients cirrhotic (CG)/non-cirrhotic (NCG). A total of 101 patients were included. Thirty of these (29.7%) were patients ≥ 70 cirrhotic. 87% of the both groups had performed > 70% of the ERAS. Oral diet tolerance and mobilization on the first postoperative day were similar in both groups. The hospital stay was similar in both groups (2.9 days/2.99 days). Morbidity and mortality were similar; Clavien I-II (CG: 44% vs NCG: 30%) and Clavien ≥ III (CG: 3% vs NCG: 8%). Hospital re-entry was higher in the NCG. Overall mortality of the study was 1%. ERAS protocol compliance was associated with a decrease in complications (ERAS < 70%: 80% vs ERAS > 90%: 20%; p: 0.02) and decrease in severity of complications in both study groups. The application of the ERAS program in cirrhotic patients who undergo liver surgery is feasible, safe, and reproducible. It allows postoperative complications, mortality, hospital stay, and readmission rates comparable to those in standard patients.

NLRP3 Contributes to Sarcopenia Associated to Dependency Recapitulating Inflammatory-Associated Muscle Degeneration.

Sarcopenia, a complex and debilitating condition characterized by progressive deterioration of skeletal muscle, is the primary cause of age-associated disability and significantly impacts healthspan in elderly patients. Despite its prevalence among the aging population, the underlying molecular mechanisms are still under investigation. The NLRP3 inflammasome is crucial in the innate immune response and has a significant impact on diseases related to inflammation and aging. Here, we investigated the expression of the NLRP3 inflammasome pathway and pro-inflammatory cytokines in skeletal muscle and peripheral blood of dependent and independent patients who underwent hip surgery. Patients were categorized into independent and dependent individuals based on their Barthel Index. The expression of NLRP3 inflammasome components was significantly upregulated in sarcopenic muscle from dependent patients, accompanied by higher levels of Caspase-1, IL-1ß and IL-6. Among older dependent individuals with sarcopenia, there was a significant increase in the MYH3/MYH2 ratio, indicating a transcriptional shift in expression from mature to developmental myosin isoforms. Creatine kinase levels and senescence markers were also higher in dependent patients, altogether resembling dystrophic diseases and indicating muscle degeneration. In summary, we present evidence for the involvement of the NLRP3/ASC/NEK7/Caspase-1 inflammasome pathway with activation of pro-inflammatory SASP in the outcome of sarcopenia in the elderly.

Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer.

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

INOCUIDAD ALIMENTARIA Y ENFERMEDADES TRANSMITIDAS POR ALIMENTOS (ETAS); SUS EFECTOS EN LA SALUD HUMANA: UNA REVISIÓN / FOOD SAFETY AND FOODBORNE DISEASES; ITS EFFECTS ON HUMAN HEALTH: A REVIEW

INTRODUCCIÓN: En la actualidad la Organización de las Naciones Unidas (ONU) como una de sus metas proyectadas al 2030 es que los alimentos sean inocuos, con seguridad alimentaria, nutritiva y suficiente, debido a que en los últimos años se ha incrementado el número de casos de Enfermedades Transmitidas por Alimentos (ETAs). La inocuidad de los alimentos es un principio básico de salud y como característica intrínseca de un alimento es que el mismo no debe causar daño a la salud. OBJETIVO: describir la importancia de la inocuidad alimentaria y los microorganismos patógenos más frecuentes que se presentan en los alimentos. METODOLOGÍA: se realizó una revisión narrativa conformada de artículos científicos a partir del año 2019 al 2023. RESULTADOS: los microoganismos que frecuentemente son causantes de las ETAs son: Salmonella, Staphylococcus aureus, E. coli, Hepatitis A, Vibrio cholerae, Listeria monocytogenes, ocasionando a nivel mundial elevados casos de diarreas relacionadas directamente con alimentos y agua contaminada, y que actualmente van en incremento. CONCLUSIÓN: las principales causas de las ETAs son por el aumento del comercio internacional de los alimentos contaminados, así como el incremento en la migración de aquellas personas que estén infectadas favoreciendo la propagación, reemergencia y aparición de microorganismos patógenos en alimentos contaminados por las malas prácticas de higiene, con la capacidad de generar infecciones, intoxicaciones y brotes en la población. Por lo anterior los organismos gubernamentales a nivel mundial, nacional y local establecen estrategias para abatir esta problemática de salud pública, pero son insuficientes, debiendo reforzar las acciones concretas de prevención y promoción.

INTRODUCTION: Due to the number of cases of Foodborne Diseases (ETAs) in recent years, the United Nations (UN) currently establishes as one of its goals for 2030 that food be safe, secure, nutritious, and sufficient. Food safety is a basic requirement, and an intrinsic characteristic of a food is that it should not negatively impact health. OBJECTIVE: to describe the importance of food safety and identify the most common pathogenic microorganisms that occur in food. Methodology: a narrative review was carried, out consisting of scientific articles from 2019 to 2023. RESULTS: the microorganisms that frequently cause ETAs are: Salmonella, Staphylococcus aureus, E. coli, Hepatitis A, Vibrio cholerae, Listeria monocytogenes, which cause frequent cases of diarrhea worldwide due to contaminated food and water, and which are currently increasing. CONCLUSION: the main causes of ETAs are the increase in international trade in contaminated foods, and the increase in the migration of people who are infected. Poor hygiene in food handling practices favor the contamination, spread, re-emergence and appearance of pathogenic microorganisms in foods, with the capacity to generate infections, poisonings and outbreaks in the population. Government agencies at the global, national, and local levels establish strategies to combat this public health problem, but they are insufficient, and specific prevention and promotion actions must be reinforced.

Influencia de la percepción de la calidad de atención sobre la salud en estudiantes universitarios / Influence of the quality perception of care on health in university students

Resumen Objetivo: La percepción de la calidad de atención al paciente es una línea de atención que ha quedado relegada en la población universitaria, ya que estos cuentan con el derecho a la atención médica por parte de la universidad, sin embargo, existen factores tanto del sector salud y universitarios que disminuyan las prácticas saludables en los estudiantes universitarios. El objetivo del presente estudio fue evaluar como perciben la calidad de atención en salud sobre la percepción y las prácticas de salud en los estudiantes de la Universidad de Quintana Roo a través de un modelo de ecuaciones estructurales. Materiales y Métodos: Se encuestaron a 401 estudiantes de la Universidad Autónoma del Estado de Quintana Roo, mayores de 20 años, 70% mujeres y 30% hombres. Se aplicaron las escalas de percepción de la calidad de atención en el servicio médico, calidad del servicio de promoción de salud por parte de la universidad y la percepción de salud en el estudiante; mediante un modelo estructural se analizó la relación entre la calidad de los servicios con el cuidado de la salud. Resultados: La percepción de una adecuada calidad de atención en las instituciones de salud y en la universidad influye significativamente en la percepción positiva de salud de los estudiantes (p<0.05). Por otra parte, se encontró que un 70% de los estudiantes no cuentan con acciones preventivas de salud. Conclusión: La percepción de salud y las prácticas preventivas pueden verse influenciadas por la calidad en los servicios que se les ofrecen en la institución de salud y en la universidad.

Abstract Objective: The quality perception of patient care is a line of care that has been relegated in the university students, since they have the right to medical care from the university, however, there are factors both in the health sector and in the university that decrease healthy practices in university students. The objective of this study was to evaluate how to perceive the quality of health care on the perception and practices of health in the students of the University of Quintana Roo through a model of structural equations. Materials and methods: A total of 401 students from the Autonomous University of the State of Quintana Roo over the age of 20, 70% women and 30% men, were surveyed. The scales of perception of the quality of care in the medical service, quality of the health promotion service by the university and the perception of health in the student were applied; Using a structural model, the relationship between the quality of services and health care was analyzed. Results: The perception of an adequate quality of care in health institutions and university influences possitively the perception of health of students (p<0.05). On the other hand, it was found that 70% of the students do not have preventive health actions. Conclusion: The perception of health and preventive practices can be influenced by the quality of the services offered at the health institution and university.

H3.1K27me1 loss confers Arabidopsis resistance to Geminivirus by sequestering DNA repair proteins onto host genome.

The H3 methyltransferases ATXR5 and ATXR6 deposit H3.1K27me1 to heterochromatin to prevent genomic instability and transposon re-activation. Here, we report that atxr5 atxr6 mutants display robust resistance to Geminivirus. The viral resistance is correlated with activation of DNA repair pathways, but not with transposon re-activation or heterochromatin amplification. We identify RAD51 and RPA1A as partners of virus-encoded Rep protein. The two DNA repair proteins show increased binding to heterochromatic regions and defense-related genes in atxr5 atxr6 vs wild-type plants. Consequently, the proteins have reduced binding to viral DNA in the mutant, thus hampering viral amplification. Additionally, RAD51 recruitment to the host genome arise via BRCA1, HOP2, and CYCB1;1, and this recruitment is essential for viral resistance in atxr5 atxr6. Thus, Geminiviruses adapt to healthy plants by hijacking DNA repair pathways, whereas the unstable genome, triggered by reduced H3.1K27me1, could retain DNA repairing proteins to suppress viral amplification in atxr5 atxr6.

Tackling potentially inappropriate prescriptions in older adults: development of deprescribing criteria by consensus from experts in Colombia, Argentina, and Spain.

BACKGROUND: Potentially inappropriate medication use is prevalent among older adults in primary care, leading to increased morbidity, adverse drug reactions, hospitalizations, and mortality. This study aimed to develop and validate a tool for identifying PIMs in older adults within the primary care setting. The tool is composed of a list of criteria and was created based on consensus among experts from three Spanish-speaking countries, including two from Latin America. METHODS: A literature review was conducted to identify existing tools, and prescription patterns were evaluated in a cohort of 36,111 older adults. An electronic Delphi method, consisting of two rounds, was used to reach a formal expert consensus. The panel included 18 experts from Spain, Colombia, and Argentina. The content validity index, validity of each content item, and Kappa Fleiss statistical measure were used to establish reliability. RESULTS: Round one did not yield a consensus, but a definitive consensus was reached in round two. The resulting tool consisted of a list of 5 general recommendations per disease, along with 33 criteria related to potential problems, recommendations, and alternative therapeutic options. The overall content validity of the tool was 0.87, with a Kappa value of 0.69 (95% CI 0.64-0.73; Substantial). CONCLUSIONS: The developed criteria provide a novel list that allows for a comprehensive approach to pharmacotherapy in older adults, intending to reduce inappropriate medication use, ineffective treatments, prophylactic therapies, and treatments with an unfavorable risk-benefit ratio for the given condition. Further studies are necessary to evaluate the impact of these criteria on health outcomes.

Prevalencia y caracterización de las neoplasias malignas en personas viviendo con VIH en Colombia / Prevalence and characterization of cancer in people living with HIV in Colombia

INTRODUCCIÓN: En el síndrome de inmunodeficiencia adquirida las neoplasias han jugado un papel preponderante, y con el advenimiento del tratamiento antirretroviral (TAR), la infección por VIH se ha transformado en una enfermedad crónica, siendo los tumores malignos una causa importante de morbilidad y mortalidad. OBJETIVO: Describir las características demográficas, clínicas y de laboratorio de las personas que viven con VIH (PVVIH) y han sido diagnosticadas con cáncer en Colombia y comparar los grupos de neoplasias definitorias y no definitorias de Sida. MÉTODOS: Revisión multicéntrica retrospectiva, en la que se recolectó y analizó datos relacionados con la infección por VIH y de diagnóstico de cáncer y tipo. Incluyó PVVIH diagnosticadas con neoplasias malignas atendidas en 23 centros de atención de pacientes con VIH en 11 ciudades de Colombia desde 1986 hasta 2018. RESULTADOS: En 23.189 pacientes, se identificaron 650 casos de malignidad (prevalencia de 2,8 % [IC de 95%: 2,6-2,9]). La neoplasia definitoria de Sida (NDS) sigue siendo el tipo de cáncer prevalente (71,1%), las neoplasias malignas más frecuentes fueron sarcoma de Kaposi (n: 330; 50,8%), linfoma no Hodgkin (n: 110; 16,9%), cáncer de piel (n: 48; 7,4%) y linfoma de Hodgkin (n: 25; 3,8%). Los pacientes con NDS tenían más probabilidades de ser HSH y estar en un estadio CDC 3, un recuento de linfocitos T CD4 < 200/μL y una carga viral del VIH ≥ 50 copias/mL al momento del diagnóstico de malignidad. Las personas con neoplasias no definitorias de Sida (NNDS) eran significativamente mayores y tenían más probabilidades de ser fumadores. CONCLUSIONES: Estos hallazgos son relevantes considerando la creciente carga de cáncer en las PVVIH que envejecen y las causas cambiantes de morbilidad y mortalidad. La presentación tardía a la atención del VIH y el retraso en el inicio del TAR son probablemente factores que contribuyen al cambio más lento hacia NNDS en comparación con las regiones de altos ingresos donde hay un acceso más rápido y temprano al TAR. El conocimiento de las tendencias epidemiológicas actuales y el perfil del cáncer en las PVVIH es fundamental para mejorar los esfuerzos de prevención y tratamiento del cáncer en el contexto de la atención integral del VIH.

BACKGROUND: In the acquired immunodeficiency syndrome, neoplasms have played a preponderant role, and with the advent of antiretroviral treatment (ART), HIV has become a chronic disease, with malignant tumors being an important cause of morbidity and mortality. AIM: To describe the demographic, clinical, and laboratory characteristics of people living with HIV (PLHIV) who have been diagnosed with cancer in Colombia and to compare the groups of AIDS-defining (ADC) and non-AIDS-defining neoplasms (NADC). METHODS: Retrospective, multicenter study that included people living with HIV/AIDS (PLHIV) diagnosed with malignancies treated at 23 HIV care centers located in 11 Colombian cities from 1986 to 2018. Data related to HIV infection and cancer diagnosis were collected and analyzed. RESULTS: Among 23,189 patients, 650 malignancy cases were identified (prevalence of 2.8% [95% CI 2.6-2.9]). AIDS-defining neoplasm remains the most prevalent type of cancer (71.1%), The most frequent individual malignancies were Kaposi sarcoma (n: 330; 50.8%), non-Hodgkin lymphoma (n: 110; 16.9%), skin cancer (n: 48; 7.4%), and Hodgkin lymphoma (n: 25; 3.8%). Compared people with NADC, with ADC were more likely to be MSM and have a CDC HIV stage 3, CD4 T cell count < 200/μL, and HIV viral load ≥ 50 copies/mL at the time of malignancy diagnosis. PLHIV and with NADC were significantly older and were more likely to be smokers. CONCLUSIONS: These findings are relevant considering the increasing burden of cancer in the aging PLHIV and the changing causes of morbidity and mortality. Late presentation to HIV care and delayed ART initiation are likely factors contributing to the slower shift toward NADCs compared with high-income regions where access to ART is better. Knowledge of the current epidemiological trends and profile of cancer in PLWHA is critical to improve cancer prevention and treatment efforts in the context of comprehensive HIV care.

Mucoadhesive polymeric systems for vaginal drug delivery: a systemic review / Sistemas poliméricos mucoadhesivos para la liberación vaginal de fármacos: revisión sistemática

ABSTRACT Intravaginal drug administration has many advantages in comparison to other delivery routes: its local and systemic effect, lower dosages, and easiness of administration. Furthermore, makes it a reliable and comfortable way of therapy. This route can be used to prevent and treat a wide range of conditions including, sexually transmitted infections (STIs), hormonal treatment, birth control, and cancer treatment. The dosage forms may vary from ovules, tablets, rings, gels, creams, films and many more; lately adding the mucoadhesiveness to the characteristics to reduce the waste of active molecules. This review focuses on the way mucoadhesive polymeric systems have been applied in vaginal delivery. This review presents a bibliographical compilation of results from various investigations published in scientific databases: Science Direct, SciELO, and PubMed Central. Results compiled demonstrate that the intravaginal drug administration can be an alternative form of medication for women with more stable and prolonged results than traditional routes requiring lower doses and avoiding the first-pass effect.

RESUMEN La administración de fármacos por vía intravaginal cuenta con múltiples ventajas a comparación de otras rutas, puede lograr un efecto tanto local como sistémico, las dosis requeridas son menores, facilidad de administración entre otras, hacen que esta forma de administración sea confiable y cómoda. Esta vía de administración puede ser empleada para prevenir y tratar diferentes trastornos, como enfermedades de transmisión sexual, desordenes hormonales, anticonceptivos y tratamiento contra el cáncer. La presentación de las dosis puede variar, desde óvulos, tabletas, anillos, geles, cremas, películas entre otros, agregando a esta, en los últimos tiempos, la característica de mucoadhesividad para reducir el desecho de moléculas activas. Este trabajo se enfoca en las aplicaciones que han tenido los sistemas poliméricos mucoadhesivos en la vía intravaginal. La bibliografía recolectada se obtuvo de bases de datos como Science direct, SciELO, y PubMed Central. Los resultados obtenidos demuestran que la administración de fármacos por vía intravaginal puede ser una forma alternativa para medicación en mujeres, con resultados más estables y prolongados que otras rutas, requiriendo menores dosis y evitando el efecto de primer paso.

La adaptación transcultural, confiabilidad y validez del instrumento actitudes y conocimientos de seguridad del paciente / The cross-cultural adaptation, reliability and validity of the instrument attitudes and knowledge of patient safety

Resumen Objetivo: La seguridad del paciente busca reducir los riesgos y ocurrencia de daño evitable, y que los errores sean menos probables en la población que recibe atención sanitaria. La formación de recursos humanos en salud es considerada como un elemento fundamental para generar cambios en la práctica sanitaria y contribuir a disminuir o limitar los errores, así como tener procesos más seguros. El objetivo de esta investigación es adaptar y validar el "Cuestionario para medir actitudes y conocimientos de seguridad del paciente" para su aplicación con estudiantes de enfermería y medicina de una Universidad Pública de Medicina y Enfermería del Caribe Mexicano. Materiales y Métodos: Estudio transversal, observacional, con aplicación de encuesta anónima y voluntaria. La muestra incluyó a 220 estudiantes (120 mujeres y 100 hombres) con una edad promedio de 24 años (DE=2) matriculados en una Universidad Pública de medicina y enfermería del Caribe Mexicano. 46% se encontraban realizando Internado de pregrado y 54% en prácticas de Servicio Social. El instrumento presentó 1 ficha de identificación y 21 reactivos tipo Likert. Resultados: A través del Análisis Factorial Exploratorio (AFE) se fijó a cinco factores con el método de Máxima Verosimilitud y rotación Varimax sobre los 21 reactivos del cuestionario de seguridad del paciente para estudiantes mexicanos, resultando una escala de cinco factores que explican el 63.59% de la varianza total y un índice de consistencia interna de la escala total aceptable (α=.87). Conclusiones: El cuestionario para medir actitudes y conocimientos sobre seguridad del paciente adaptado en los estudiantes de medicina y enfermería es válido, confiable y útil para medir las acciones de seguridad del paciente para la prevención del error en la atención sanitaria.

Abstract Objective: Patient safety seeks to reduce the risk and occurrence of avoidable harm, and to make errors less common in the population that receive health care. The training of human resources in health is considered a fundamental element to generate changes in health practices and contribute to reducing errors, furthermore safer processes. The objective of the present study is adapt and validate the "Questionnaire to measure attitudes and knowledge of patient safety" for its application with nursing and medical students of Public University of Medicine and Nursing in the Mexican Caribbean. Materials and methods: A cross-sectional, observational study, with the application of an anonymous and voluntary survey. The sample included 220 students (120 women and 100 men) with an average age of 24 years (SD=2) a Public University of Medicine and Nursing in the Mexican Caribbean. The 46% were undergraduate internship and 54% in Social Service practices. The instrument presented one identification card and 21 Likert-type items. Results: Through the Exploratory Factor Analysis (EFA), five factors were set with the Maximum Likelihood method and Varimax rotation on the 21 items of the patient safety questionnaire for Mexican students, resulting five factors that explain 63.59% of the total variance and an internal consistency index of the acceptable total scale (α=.87). Conclusions: The questionnaire to measure attitudes and knowledge about patient safety translated and adapted to medical and nursing students is valid, reliable and useful to measure patient safety actions for the prevention of errors in health care.

COVID-19 in Pediatric Cancer Patients and Hematopoietic Stem Cell Transplant Recipients in a Tertiary Care Hospital in Argentina.

The outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer pediatric patients was initially uncertain. The objective of this study was to describe the characteristics and outcome of cancer patients and hematopoietic stem cell transplant recipients from 0 to 19 years with detectable SARS-CoV-2 from April 23, 2020, to April 30, 2022, treated in a tertiary-level hospital in Argentina. A total of 348 cases were registered in 339 patients. The median age was 89.5 (3 to 224) months. The sex was predominantly male: 193 (55.5%). The most common malignant disease was leukemia (42.8%). One hundred four cases (29.9%) had comorbidities. Of the 346 cases with an available blood count, 17.6% had a lymphocyte count <300/mm 3 . Fever was the most common symptom. In most cases (93.1%) presented asymptomatic or mild disease. Twenty-one cases (6%) presented severe or critical status. Eleven of 24 admissions to the intensive care unit were due to COVID-19 (coronavirus disease 2019). Eight patients (2.3%) died. Two deaths were attributable to SARS-CoV-2 (0.6%). Being older, having fever, lymphopenia at diagnosis, and having received hematopoietic stem cell transplant were associated with a more severe disease. Around 90% of the children continued their cancer treatment without any change.

The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation.

Immune cell trafficking constitutes a fundamental component of immunological response to tissue injury, but the contribution of intrinsic RNA nucleotide modifications to this response remains elusive. We report that RNA editor ADAR2 exerts a tissue- and stress-specific regulation of endothelial responses to interleukin-6 (IL-6), which tightly controls leukocyte trafficking in IL-6-inflamed and ischemic tissues. Genetic ablation of ADAR2 from vascular endothelial cells diminished myeloid cell rolling and adhesion on vascular walls and reduced immune cell infiltration within ischemic tissues. ADAR2 was required in the endothelium for the expression of the IL-6 receptor subunit, IL-6 signal transducer (IL6ST; gp130), and subsequently, for IL-6 trans-signaling responses. ADAR2-induced adenosine-to-inosine RNA editing suppressed the Drosha-dependent primary microRNA processing, thereby overwriting the default endothelial transcriptional program to safeguard gp130 expression. This work demonstrates a role for ADAR2 epitranscriptional activity as a checkpoint in IL-6 trans-signaling and immune cell trafficking to sites of tissue injury.

Levels of Pro-Inflammatory and Bone-Resorptive Mediators in Periodontally Compromised Patients under Orthodontic Treatment Involving Intermittent Forces of Low Intensities.

During orthodontic treatment, diverse cytokines, enzymes, and osteolytic mediators produced within the teeth surrounding periodontal tissues determine the rate of alveolar bone remodeling and consequent teeth movement. In patients with teeth presenting reduced periodontal support, periodontal stability should be ensured during orthodontic treatment. Thus, therapies based on the application of low-intensity intermittent orthodontic forces are recommended. To determine if this kind of treatment is periodontally well tolerated, this study aimed to analyze the production of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, IL-17A, and matrix metalloproteinase (MMP)-8 in periodontal tissues of protruded anterior teeth with reduced periodontal support and undergoing orthodontic treatment. Patients with periodontitis-associated anterior teeth migration received non-surgical periodontal therapy and a specific orthodontic treatment involving controlled low-intensity intermittent orthodontic forces. Samples were collected before periodontitis treatment, after periodontitis treatment, and at 1 week to 24 months of the orthodontic treatment. During the 2 years of orthodontic treatment, no significant differences were detected in the probing depth, clinical attachment level, supragingival bacterial plaque, and bleeding on probing. In line with this, the gingival crevicular levels of RANKL, OPG, IL-6, IL-17A, and MMP-8 did not vary between the different evaluation time-points of the orthodontic treatment. When compared with the levels detected during the periodontitis, the RANKL/OPG ratio was significantly lower at all the analyzed time-points of the orthodontic treatment. In conclusion, the patient-specific orthodontic treatment based on intermittent orthodontic forces of low intensities was well tolerated by periodontally compromised teeth with pathological migration.

Complicaciones de la técnica anestésica mandibular Spix en la clínica odontológica de la Universidad Andrés Bello / Incidence of complications of mandibular anesthetic Spix techniques in the Andrés Bello University dental clinic

Objetivo: Determinar la incidencia de complicaciones de la técnica anestésica Spix en procedimientos odontológicos a pacientes atendidos en la clínica de la Universidad Andrés Bello (UNAB). Material y Métodos: Se analizó a 37 pacientes que fueron atendidos por alumnos de cuarto y quinto año de la clínica odontológica, a los cuales se le realizó la técnica anestésica Spix para realizar el procedimiento odontológico. Se consignó mediante la observación la presencia de formación de hematomas intraorales en el sitio de punción, rotura de la aguja, cantidad de tubos de solución anestésica inyectados, presencia de dolor a la inyección de solución anestésico y la presencia o no de parálisis facial. Mediante la recolección de datos y posterior encuesta a los participantes se consignó la presencia de trismus al día siguiente de la atención y parestesia persistente al día siguiente de la atención. Resultados: De 37 pacientes estudiados que recibieron la técnica anestésica Spix, 6 presentaron hematoma intraoral (16,2%), ninguno reportó rotura de la aguja, 1 presentó parálisis facial (2,7%), 1 presentó parestesia persistente al día siguiente (2,7%), 12 presentaron trismus posterior a la inyección (32,4%). El rango de dolor reportado fue entre 1 y 4 según la escala EVA. Conclusión: Hay una baja incidencia de las complicaciones asociadas a la técnica anestésica Spix en la clínica odontológica de la UNAB, siendo el trismus la complicación más frecuente. Se necesita un mayor número de muestra para entender mejor esta realidad.

Objective: To determine the incidence of complications of the Spix anesthetic technique in the dental procedures of patients attended at the Andrés Bello University dental clinic. Material and Methods: 37 patients who were cared for by fourth- and fifth-year students from the dental clinic of the Andrés Bello University were analyzed, who underwent the Spix anesthetic technique to perform the dental procedure. The presence of intraoral hematoma formation at the puncture site, needle breakage, number of injected anesthesia tubes, presence of pain upon injection of anesthetic and the presence or not of facial paralysis were recorded. Through data collection and subsequent survey of the participants, the presence of trismus was recorded the day after care. Results. Of the 37 cases of patients studied who received the Spix anesthetic technique, 6 had intraoral hematoma (16.2%), no needle break was reported, 1 had facial paralysis (2.7%), 1 had persistent paresthesia at the next day (2.7%), 12 presented trismus after the injection (32.4%), the pain range was between 1 and 4 according to the VAS scale. Conclusion. There is a low incidence of complications associated with the Spix anesthetic technique in the Andrés Bello University dental clinic, trismus being the most frequent (32.4%). A larger sample number should be needed to better understand this reality.

Exposure of 4-year to 24-year olds to tobacco imagery on prime-time Chilean television.

INTRODUCTION: The extent of the population's exposure to tobacco imagery across all genres of regular TV programming and the contribution of each of these genres is unknown, except for UK broadcast channels. The objective of this study is to estimate the exposure of young people to tobacco imagery on Chilean prime-time television and the programme source contributing to such exposure. METHODS: Programmes aired during 3 weeks in 2019 from the 15 highest audience channels in Chile were content-analysed for the occurrence of tobacco categorised as actual use, implied use, tobacco paraphernalia, tobacco brand appearances and whether they violated Chilean smoke-free law for each 1 min interval (92 639). The exposure of young people to tobacco content was estimated using media viewership figures. RESULTS: Young people received 29, 11 and 4 million tobacco impressions of any type, explicit use and smoke-free violation, respectively, at a rate of 21.8, 8.0 and 2.1 thousand impressions per hour of TV viewing. The main sources of exposure to tobacco impressions were feature films and animated productions, which were almost entirely non-Chilean. Finally, young people were exposed to tobacco brand impressions primarily through films, effectively circumventing the advertising ban in Chile. DISCUSSION: Television programming is a source of significant youth exposure to tobacco imagery, including branding impressions. To conform to the WHO FCTC, Chile should prohibit tobacco branding in any TV programme and require strong anti-tobacco advertisements prior to any TV programme portraying tobacco.