Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability.

Tumor suppressor p53 (TP53) is frequently mutated in cancer, often resulting not only in loss of its tumor-suppressive function but also acquisition of dominant-negative and even oncogenic gain-of-function traits. While wild-type p53 levels are tightly regulated, mutants are typically stabilized in tumors, which is crucial for their oncogenic properties. Here, we systematically profiled the factors that regulate protein stability of wild-type and mutant p53 using marker-based genome-wide CRISPR screens. Most regulators of wild-type p53 also regulate p53 mutants, except for p53 R337H regulators, which are largely private to this mutant. Mechanistically, FBXO42 emerged as a positive regulator for a subset of p53 mutants, working with CCDC6 to control USP28-mediated mutant p53 stabilization. Additionally, C16orf72/HAPSTR1 negatively regulates both wild-type p53 and all tested mutants. C16orf72/HAPSTR1 is commonly amplified in breast cancer, and its overexpression reduces p53 levels in mouse mammary epithelium leading to accelerated breast cancer. This study offers a network perspective on p53 stability regulation, potentially guiding strategies to reinforce wild-type p53 or target mutant p53 in cancer.

Cluster Analysis of Factors Associated with Leishmaniasis in Peru.

OBJECTIVE: To analyze the factors associated with leishmaniasis in Peru, according to the cluster classification in the period 2017-2021. METHODS: Quantitative approach, with an ecological, descriptive correlational, and cross-sectional design. The population was from the geographical region of Peru, where a total of 26,956 cases of leishmaniasis were registered by the Peruvian Ministry of Health from 2017 to 2021. Spearman's Rho statistic was used to analyze the variables that are most associated with the cases of leishmaniasis reported per year, and, in addition, the multivariate technique of cluster analysis was applied. RESULTS: Annual rainfall and areas with humid forest (climatic factors) and mortality from transmissible diseases (health factor) are directly associated with reported cases of leishmaniasis. Households with basic access to infrastructure, drinking water, drainage, and electric lighting; illiteracy, regional social progress, and unsatisfied basic needs (social factors); and percentage of urban population (demographic factor) are inversely and significantly associated with cases of leishmaniasis. CONCLUSIONS: Climatic and environmental factors contribute to the multiplication of the leishmaniasis disease vector. The incidence of leishmaniasis adds up to the mortality rates for transmissible diseases in Peru. As living conditions improve, the incidence of this pathology decreases.

Validity and Reliability of the Knowledge, Attitudes and Practices Instrument Regarding Monkey Pox in Peru.

Objective: To analyze the questionnaire of the validity and reliability of knowledge, attitudes and practices concerning Mpox. Methods: This was an instrumental, cross-sectional study. The sample consisted of 178 citizens from 3 sectors of Peru, who responded to a virtual questionnaire regarding knowledge, attitudes and practices concerning Mpox. The validity and reliability process of the questionnaire was carried out using Aiken's V, Cronbach's Alpha, McDonald's Omega and principal component analysis. Results: After expert evaluation, the questionnaire was shown to have adequate content validity for measuring knowledge, attitudes and practices concerning Mpox, each in their respective dimensions, with Aiken's V values above 0.90. For construct validity, exploratory factor analysis was used and the items were grouped into four dimensions for the level of knowledge, three dimensions for attitudes, and two for practices. With respect to the reliability analysis, the application of Cronbach's α statistic and McDonald's ω, obtained values above 0.70. Conclusion: The results of the research enabled the attainment of a questionnaire that meets the adequate psychometric characteristics in order to be applied.

Microencapsulation of a Native Strain of the Entomopathogenic Fungus Beauveria bassiana and Bioinsecticide Activity against Pyrethroid-Resistant Triatoma infestans to Vector Control of Chagas Disease in the Argentine Gran Chaco Region.

The blood-sucking bug Triatoma infestans is the main Chagas disease vector in the Southern Cone of Latin America. Populations resistant to pyrethroid insecticides have been detected in the early 2000s and then expanded to the endemic area of northern Salta province, Argentina. In this context, the entomopathogenic fungus Beauveria bassiana has been shown to be pathogenic to pyrethroid-resistant T. infestans. In this study, both the bioinsecticidal activity and the residual effect of an alginate-based microencapsulation of a native strain of B. bassiana (Bb-C001) were tested under semi-field conditions against pyrethroid-resistant T. infestans nymphs. Fungal microencapsulated formulation caused higher nymph mortality than the unmicroencapsulated fungus and contributed to maintaining the conidial viability throughout the period evaluated under the tested conditions. These results suggest that alginate microencapsulation is an effective, simple, low-cost method that could be incorporated into the formulation of a bioinsecticide as a strategy to reduce the vector transmission of Chagas disease.

Discrimination of dyslipidemia types with ATR-FTIR spectroscopy and chemometrics associated with multivariate analysis of the lipid profile, anthropometric, and pro-inflammatory biomarkers.

BACKGROUND: Obesity, dyslipidemia, and low-grade inflammatory state form a triad of self-sustaining metabolic dysfunction. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy is a simple, rapid, and non-destructive technique that generates spectral fingerprints of biomolecules that can be correlated with metabolic changes. We verified the efficiency of ATR-FTIR spectroscopy in blood plasma (n = 74) to discriminate the types of dyslipidemias and suggest metabolic inflammatory changes. METHODS: Principal Component Analysis (PCA) was performed on the biochemical and anthropometric data to verify whether the dyslipidemia types share a similar biochemical profile plausible of discrimination in chemometric modeling. To discriminate the types of dyslipidemias based on spectral data, Orthogonal Partial Least-Squares Discriminant Analysis (OPLS-DA) was used and validated with leave-one-out cross-validation. RESULTS: Although no significant difference was obtained between the types of dyslipidemia and normal subjects by CRP, leptin, and cfDNA, there was a significant difference between normal subjects vs combined hyperlipidemia (CH) + hypercholesterolemia (HCL) + hypertriglyceridemia (HTG) (p < 0.05) by the 1245 cm-1 peak [νas(PO2-)] (possible indication of chronic inflammation by increased cfDNA). The area under the curve of the region between 1770 and 1720 cm-1 was significantly increased for CH in relation to other dyslipidemias and normal subjects. Furthermore, there were significant differences for the main representative peaks of lipids, proteins, carbohydrates, and nucleic acids between the types of dyslipidemias and between the types of dyslipidemias and normal subjects. The OPLS-DA model achieved 100 % accuracy with 1 latent variable and Standard Error of Cross-Validation (SECV) < 0.004 for all types of dyslipidemia  and the control group. CONCLUSIONS: Our results suggest that ATR-FTIR spectroscopy associated with chemometric modeling is a plausible applicant for screening the types of dyslipidemias. However, more extensive studies should be conducted to verify the real applicability in clinical analysis laboratories or medical clinics.

Evolution of SLiM-mediated hijack functions in intrinsically disordered viral proteins.

Viruses and their hosts are involved in an 'arms race' where they continually evolve mechanisms to overcome each other. It has long been proposed that intrinsic disorder provides a substrate for the evolution of viral hijack functions and that short linear motifs (SLiMs) are important players in this process. Here, we review evidence in support of this tenet from two model systems: the papillomavirus E7 protein and the adenovirus E1A protein. Phylogenetic reconstructions reveal that SLiMs appear and disappear multiple times across evolution, providing evidence of convergent evolution within individual viral phylogenies. Multiple functionally related SLiMs show strong coevolution signals that persist across long distances in the primary sequence and occur in unrelated viral proteins. Moreover, changes in SLiMs are associated with changes in phenotypic traits such as host range and tropism. Tracking viral evolutionary events reveals that host switch events are associated with the loss of several SLiMs, suggesting that SLiMs are under functional selection and that changes in SLiMs support viral adaptation. Fine-tuning of viral SLiM sequences can improve affinity, allowing them to outcompete host counterparts. However, viral SLiMs are not always competitive by themselves, and tethering of two suboptimal SLiMs by a disordered linker may instead enable viral hijack. Coevolution between the SLiMs and the linker indicates that the evolution of disordered regions may be more constrained than previously thought. In summary, experimental and computational studies support a role for SLiMs and intrinsic disorder in viral hijack functions and in viral adaptive evolution.

Modelo logístico de factores asociados al Síndrome de Burnout en el personal de salud / Logistic model of factors associated with Burnout Syndrome in health personnel

Introducción: La carga de trabajo excesiva en el personal de salud, debido a la pandemia del COVID-19 ha generado la presencia del Síndrome de Burnout. El propósito de este estudio fue determinar un modelo logístico para los factores asociados a las dimensiones del Síndrome de Burnout en el personal de salud, durante la pandemia COVID-19, en Trujillo - Perú. Método: Se aplicó un diseño transversal, correlacional; se utilizó el cuestionario estandarizado del inventario de Burnout de Maslach aplicado virtualmente, que mide: agotamiento emocional, despersonalización y realización personal, la muestra estuvo conformada por 143 profesionales de salud de los establecimientos de la Micro red de Trujillo y de El Seguro Social de Salud (ESSALUD), Resultados: El 24,5% de profesionales de la salud tienen un nivel de agotamiento emocional alto, 27,3% nivel de despersonalización alto y 39,9% nivel de realización personal bajo. El estado civil, ingreso familiar, tipo de institución donde labora, la edad y el número de hijos se asocian al nivel de agotamiento emocional (p<0,05). El sexo, la profesión, tipo de institución, edad y número de hijos se asocian al nivel de despersonalización (p<0,05). El tipo de institución y la edad se asocian al nivel de realización personal (p<0,05).Conclusiones: El modelo logístico ordinal propuesto indica el 69,2% de éxito en nivel de agotamiento emocional, el 60,8% de éxito para el nivel de despersonalización y el 58,7% con el modelo para nivel de realización personal. (AU)

Introduction: Excessive workload in health personnel, due to the COVID-19 pandemic, has generated the presence of Burnout Syndrome. The purpose of this study was to determine a logistic model for the factors associated with the dimensions of Burnout Syndrome in health personnel during the COVID-19 pandemic in Trujillo - Peru. Method: A cross-sectional, correlational design was applied. The standardized Maslach Burnout Inventory questionnaire was used and applied virtually. It measures emotional exhaustion, depersonalization and personal fulfillment. The sample consisted of 143 health professionals from the Trujillo Micro-network and Social Health Insurance establishments (ESSALUD). Results: 24.5% of health professionals have a high level of emotional exhaustion, 27.3% a high level of depersonalization and 39.9% a low level of personal fulfillment. Marital status, family income, type of institution where they work, age and number of children are associated with the level of emotional exhaustion (p<0.05). Gender, profession, type of institution, age and number of children are associated with the level of depersonalization (p<0.05). The type of institution and age are associated with the level of personal fulfillment (p<0.05). Conclusions: The proposed ordinal logistic model indicates 69.2% success in emotional exhaustion level, 60.8% success for depersonalization level and 58.7% with the model for personal fulfillment level. (AU)

Factors Associated with the Acceptance of COVID-19 Vaccines in Citizens of Northern Peru: Cross-Sectional Study.

Purpose: The presence of the COVID-19 coronavirus in Peru, and especially in northern Peru, was very fast and caused many deaths. As a result, vaccination proved to be the most immediate option to control it. However, a sector of the population was reluctant to vaccination. Therefore, this study aimed to analyze the factors associated with the acceptance of COVID-19 vaccines by citizens of northern Peru. Patients and Methods: The study was observational, descriptive-correlational and the sample was stratified and consisted of 516 citizens from eight departments of northern Peru, who answered an online questionnaire regarding sociodemographic, cultural and health aspects. The data were analyzed using statistical tests of association and a logistic model was estimated to identify factors predicting vaccine acceptance. Results: Among the factors associated with vaccine acceptance, sociodemographic factors such as age and family income, cultural factors such as level of knowledge, and health factors such as having another chronic disease and a vaccine with a higher confidence (p<0.05) were found. In addition, 12% of the population do not trust them, 10% are afraid that they may cause thrombosis, 13% disagree with vaccination for children, 7% think that a chip will be implanted and 8% believe that their DNA will be changed. However, most people accept vaccination and consider it necessary. A multivariate analysis was also performed for the acceptance of vaccines, which presented a percentage of 80.2% correct in the prognosis. Conclusion: The multivariate analysis allowed a conclusion that the predictor variables for vaccine acceptance are household income of less than 1000 Peruvian soles per month, low or medium levels of knowledge, and having another chronic disease.

Evaluación biológica in vitro del extracto etanólico de Kaa tái, Polygonum punctatum Elliot. (POLYGONACEAE)

En Paraguay, así como en las Américas, la leishmaniasis constituye una de las problemáticas de salud pública importante, debido a su complejidad tanto epidemiológica, clínica y biológica, afectando especialmente a los más pobres y en los países en vía de desarrollo. Polygonum punctatum Elliot. pertenece a la familia Polygonaceae, la medicina popular le atribuye varias propiedades, por medio de estudios anteriores se confirma que diferentes extractos de esta planta presentan actividad antibacteriana, antiinflamatoria y antifúngica. En este trabajo, se evaluó la actividad citotóxica del extracto etanólico de Polygonum punctatum de la familia Polygonaceae en concentraciones de 100, 50 y 25 µg/ml en células de macrófagos de ratones, en los cuales no se encontró actividad citotóxica. Además, se evaluó la actividad leishmanicida por medio de estudios experimentales in vitro a concentraciones de 100, 75, 50, 25, 20 y 10 µg/ml frente a tres cepas de parásitos: Leishmania infantum, L. amazonensis y L. braziliensis, en los cuales se observó una actividad de 58 y 56% de lisis de parásitos con el extracto de 100µg/ml frente a las cepas de L. braziliensis y L. infantum, respectivamente y 51% para L. amazonensis. Estos resultados son prometedores, y aportan una base para el desarrollo y búsqueda de nuevos tratamientos para la leishmaniasis, sin embargo, son necesarios estudios posteriores en cuanto a aislamiento e identificación del compuesto y evaluación en modelos animales in vivo.

In Paraguay, as well as in the Americas, leishmaniasis constitutes one of the important public health problems, due to its epidemiological, clinical, and biological complexity, especially affecting the poorest and developing countries. Polygonum punctatum Elliot belongs to the Polygonaceae family, and popular medicine attributes several properties to it. Previous studies confirmed that different extracts of this plant have antibacterial, anti-inflammatory and antifungal activity. In this work, the cytotoxic activity of the ethanolic extract of Polygonum punctatum was evaluated at concentrations of 100, 50 and 25 µg/ml in mouse macrophage cells, in which no cytotoxic activity was found. In addition, the leishmanicidal activity was evaluated through experimental in vitro studies at concentrations 100, 75, 50, 25, 20 and 10 µg/ml against three strains of parasites: Leishmania infantum, L. amazonensis and L. braziliensis. Activities of 58 and 56% of parasite lysis were observed with the 100 µg/ml extract against strains of L. braziliensis and L. infantum, respectively, and 51% for L. amazonensis. These results are promising and provide a basis for the development and search of a new treatment for leishmaniasis. However, further studies are necessary regarding the isolation and identification of the compound and its evaluation in in vivo animal models.

Predicting the effect of disordered linkers on effective concentrations and avidity with the "Ceff calculator" app.

Linkers are crucial to the functions of multidomain proteins as they couple functional units to encode regulation such as auto-inhibition, enzyme targeting or tuning of interaction strength. A linker changes reactions from bimolecular to unimolecular, and the equilibrium and kinetics is thus determined by the properties of the linker rather than concentrations. We present a theoretical workflow for estimating the functional consequences of tethering by a linker. We discuss how to: (1) Identify flexible linkers from sequence. (2) Model the end-to-end distance distribution for a flexible linker using a worm-like chain. (3) Estimate the effective concentration of a ligand tethered by a flexible linker. (4) Calculate the decrease in binding affinity caused by auto-inhibition. (5) Calculate the expected avidity enhancement of a bivalent interaction from effective concentration. The worm-like chain modeling is available through a web application called the "Ceff calculator" (http://ceffapp.chemeslab.org), which will allow user-friendly prediction of experimentally inaccessible parameters.

Isolation of Beauveria bassiana from the Chagas Disease Vector Triatoma infestans in the Gran Chaco Region of Argentina: Assessment of Gene Expression during Host-Pathogen Interaction.

A native strain of the entomopathogenic fungus Beauveria bassiana (Bb-C001) was isolated from a naturally infected Triatoma infestans, Klug (Hemiptera: Reduviidae) adult cadaver in the Gran Chaco region, Salta province, Argentina. The isolate was both phenotypic and molecularly characterized in a context of fungus-insect interaction, by measuring the expression pattern of toxin genes during infection and immune response of T. infestans. The commercial strain GHA of B. bassiana, which was previously used in field interventions to control these vectors, was used as reference in this study. The phylogenetic trees based on both ribosomal internal transcribed spacer (ITS) and elongation factor 1-alpha (EF1-α) indicated that Bb-C001 fits into a B. bassiana cluster, and the sequence-characterized amplified regions (SCAR) showed that Bb-C001 is different from the GHA strain. There were no differences between both strains regarding viability, radial growth, and conidia production, either in the median survival time or insect mortality. However, Bb-C001 showed a higher expression than GHA of the bassianolide synthetase gene (BbbslS) during infection, and similar levels of the beauvericin synthetase gene (BbbeaS). Immune-related genes of T. infestans nymphs (limpet-2 and defensin-1, -2, and -6) were later expressed and thus insects failed to stop the infection process. These results showed that B. bassiana Bb-C001 is a promised fungal strain to be incorporated in the current biological control programs of T. infestans in Salta province, Argentina.

Manejo de una fractura corono-radicular complicada / Management of a complicated crown-root fracture

En la práctica odontológica se presentan casos de fracturas corono radiculares complicadas, que representan un dilema al momento del abordaje del tratamiento; ya que el segmento coronal se encuentra con movilidad, pero el remanente cuenta con suficiente tejido dental para retenerse. La porción radicular de la fractura es capaz de soportar la rehabilitación, pero es difícil la preparación porque existe pobre visibilidad y es imposible su acceso. Objetivo. Implementar la técnica de extrusión quirúrgica intencional como tratamiento alternativo a la exodoncia, para mantener por más tiempo en cavidad oral al órgano dental afectado. Metodología. Se presenta el manejo clínico de un paciente masculino de 26 años de edad, que acude a la consulta odontológica tras sufrir un accidente de tránsito. Conclusiones. La técnica de extrusión quirúrgica intencional es efectiva para dientes fracturados que cumplen los criterios de selección, ya que permite la conservación del órgano dental y reestablece sus funciones

In dental practice, there are cases of complicated crown root fractures, which represent a dilemma when approaching treatment; since the coronal segment is mobile, but the remnant has enough dental tissue to be retained. The root portion of the fracture is capable of supporting rehabilitation, but preparation is difficult because there is poor visibility and access is impossible. Objective. Implement the intentional surgical extrusion technique as an alternative treatment to extraction, to keep the affected dental organ in the oral cavity for a longer time. Methodology. The clinical management of a 26-year-old male patient is presented, who comes to the dental office after suffering a traffic accident. Conclusions. The intentional surgical extrusion technique is effective for fractured teeth that meet the selection criteria, as it allows the preservation of the dental organ and restores its functions

In silico Strategies to Support Fragment-to-Lead Optimization in Drug Discovery.

Fragment-based drug (or lead) discovery (FBDD or FBLD) has developed in the last two decades to become a successful key technology in the pharmaceutical industry for early stage drug discovery and development. The FBDD strategy consists of screening low molecular weight compounds against macromolecular targets (usually proteins) of clinical relevance. These small molecular fragments can bind at one or more sites on the target and act as starting points for the development of lead compounds. In developing the fragments attractive features that can translate into compounds with favorable physical, pharmacokinetics and toxicity (ADMET-absorption, distribution, metabolism, excretion, and toxicity) properties can be integrated. Structure-enabled fragment screening campaigns use a combination of screening by a range of biophysical techniques, such as differential scanning fluorimetry, surface plasmon resonance, and thermophoresis, followed by structural characterization of fragment binding using NMR or X-ray crystallography. Structural characterization is also used in subsequent analysis for growing fragments of selected screening hits. The latest iteration of the FBDD workflow employs a high-throughput methodology of massively parallel screening by X-ray crystallography of individually soaked fragments. In this review we will outline the FBDD strategies and explore a variety of in silico approaches to support the follow-up fragment-to-lead optimization of either: growing, linking, and merging. These fragment expansion strategies include hot spot analysis, druggability prediction, SAR (structure-activity relationships) by catalog methods, application of machine learning/deep learning models for virtual screening and several de novo design methods for proposing synthesizable new compounds. Finally, we will highlight recent case studies in fragment-based drug discovery where in silico methods have successfully contributed to the development of lead compounds.

"Nós estamos grávidos": rituais de cuidado desenvolvidos por famílias durante o processo gestacional / "Estamos embarazados": rituales de atención desarrollados por las familias durante el proceso gestacional / "We are pregnant": care rituals developed by families during the gestational process

Objetivo: conhecer os rituais de cuidado desenvolvidos pelas famílias durante o processo gestacional. Método: pesquisa etnográfica, desenvolvida entre abril e dezembro de 2016, com três famílias que vivenciavam o processo gestacional e profissionais de saúde que as acompanhavam, em um município da região central do estado do Rio Grande do Sul. Adotou-se o modelo de Observação-Participação-Reflexão, com entrevista complementar. A análise fundamentou-se na etnoenfermagem. Resultados: os rituais de cuidado estavam ligados à revelação da gestação, à alimentação, à utilização de homeopatia e chás, à reorganização familiar, à preparação do quarto do bebê, às vestimentas do bebê, ao chá de fraldas, às escolhas futuras da criança, ao apadrinhamento e ao registro da gestação. Conclusão: os rituais de cuidado constituem elementos culturais essenciais para o cuidado à saúde da família grávida. Eles integram os familiares, mantém e fortalecem a identidade e a cultura familiar e renovam os elementos que compõem a família.

Objective: to understand the care rituals developed by families during the gestational process. Method: ethnographic research, carried out between April and December 2016, with three families who experienced the gestational process and health professionals that accompanied them, in a city in the central region of the state of Rio Grande do Sul. The model adopted was the Observation-Participation-Reflection, with supplementary interview. The analysis was based on the ethnonursing. Results: the care rituals were related to the revelation of the pregnancy, nutrition, the use of homeopathy and teas, family reorganization, the preparation of the baby's room, the baby clothing, diaper shower, to the future choices of the child, godparents and the record of the pregnancy. Conclusion: care rituals constitute cultural elements essential for the health care of the pregnant family. They are part of the family, maintaining and strengthening the family identity and culture and renewing the elements that compose the family.

Objetivo: comprender los rituales de cuidado desarrollados por las familias durante el proceso de gestación. Método: investigación etnográfica, llevada a cabo entre abril y diciembre de 2016, con tres familias que experimentaron el proceso gestacional y los profesionales de la salud que las acompañaron, en un municipio de la región central del estado de Rio Grande do Sul. Se adoptó el modelo Observación-Participación-Reflexión, con entrevista complementaria. El análisis se basó en la etnoenfermería. Resultados: los rituales de cuidado estaban relacionados con la revelación del embarazo, la nutrición, el uso de la homeopatía y tés, y a la reorganización de la familia, la preparación de la habitación del bebé, la ropa del bebé, fiesta de pañales, las opciones futuras del niño, apadrinamiento y el registro del embarazo. Conclusión: los rituales de cuidado constituyen elementos culturales esenciales para el cuidado de la salud de la familia embarazada. Ellos son parte de la familia, mantienen y refuerzan la identidad y la cultura de la familia y renuevan los elementos que componen la familia.

Vivências do período gravídico-puerperal na perspectiva de mulheres adolescentes / Experiences from the puerperal period according to the viewpoint of adolescent women / Vivencias del período gravídico puerperal en la perspectiva de mujeres adolescentes

Objetivo: Conhecer como a mulher adolescente vivencia o período gravídico-puerperal. Método: Estudo qualitativo descritivo. As participantes foram 11 puérperas adolescentes. Para coleta de dados utilizou-se a entrevista semiestruturada e o mapa falante. Os dados foram submetidos à análise de conteúdo temática da proposta operativa. Resultados: Revelaram que no início da gestação sentiram insegurança, medo e rejeição; passaram por alguns abandonos e afastamentos; tiveram que reorganizar os planos de vida; os estudos foram adiados; mas, ao final, prevaleceu o sentimento de felicidade ao ter o filho nos braços. Conclusão: conhecer a vivência do período gravídico-puerperal das adolescentes permitiu compreender a importância do profissional de saúde atuar neste contexto e poder contribuir para evolução de uma gestação saudável a partir da compreensão das singularidades das adolescentes

Objective: The study's purpose has been to know how the adolescent woman experience the pregnancypuerperal period. Methods: It is a descriptive study with a qualitative approach. The participants were 11 adolescents who have recently given birth. Data collection took place through a semi-structured interview and the taking map. The data were submitted to thematic content analysis according to the operative proposal. Results: Data have revealed that women felt insecurity, fear and rejection during the initial stages of pregnancy; they faced abandonment; they also had to rearrange their life plans; their studies were put aside and delayed; but, after all, the feeling of happiness by having their children together has prevailed. Conclusion: Experiencing the pregnancy-puerperal period allowed the adolescent women to understand the importance of health professionals participating of this context and being able to contribute to a healthy pregnancy by appreciating the adolescents' specificities

Objetivo: Conocer cómo el adolescente mujer viviendo el periodo grávido puerperal. Método: estudio descriptivo cualitativo. Los participantes eran 11 adolescentes que han dado a luz recientemente. Para datos colección utilizó la entrevista semiestructurada y el mapa. Los datos fueron sometidos a análisis de contenido temático de la propuesta operativa. Resultados: reveló que temprano en el embarazo se sentía inseguridad, temor y rechazo; fue a través de algunas salidas y llegadas; tuvo que reorganizar los planes de vida; los estudios fueron retrasados; pero, al final, prevaleció el sentimiento de felicidad para que el niño en sus brazos. Conclusión: llegar a conocer que la experiencia de los adolescentes el período grávidos permitido entender la importancia puerperal de profesional de la salud actuar en este contexto y ser capaces de contribuir a un embarazo saludable de la comprensión de las singularidades de los adolescentes

Current Drug Nano-targeting Strategies for Improvement in the Diagnosis and Treatment of Prevalent Pathologies such as Cardiovascular and Renal Diseases.

BACKGROUND: The kidney and cardiovascular system are closely related to each other during the modulation of the cardiovascular homeostasis. However, the search for new alternatives for the treatment and diagnosis of cardiovascular diseases does not take into account this relationship, so their evaluation results and the advantages offered by their global and integrative analysis are wasted. For example, a variety of receptors that are overexpressed in both pathologies is large enough to allow expansion in the search for new molecular targets and ligands. Nanotechnology offers pharmacological targeting strategies to kidney, heart, and blood vessels for overcoming one of the essential restrictions of traditional cardiovascular therapies the ones related to their unspecific pharmacodynamics distribution in these critical organs. RECENT FINDINGS: Drug or contrast agent nano-targeting for treatment or diagnosis of atherosclerosis, thrombosis, renal cancer or fibrosis, glomerulonephritis, among other renal, cardiac and blood vessels pathologies would allow an increase in their efficacy and a reduction of their side effects. Such effects are possible because, through pharmacological targeting, the drug is mainly found at the desired site. Review Purpose: In this mini-review, active, passive, and physical targeting strategies of several nanocarriers that have been assessed and proposed for the treatment and diagnosis of different cardiovascular diseases, are being addressed.

"Vem passando de geração para geração": as práticas de cuidados de mulheres quilombolas / "Going from generation to generation": Caring practices for quilombola women / "Pasado de generación en generación": las prácticas de cuidado de las mujeres quilombolas

Objetivo: investigar como foram construídas socioculturalmente as práticas de cuidado entre mulheres de uma comunidade quilombola. Método: pesquisa qualitativa, descritiva, com vertente antropológica, desenvolvida com mulheres quilombolas. Os dados, produzidos a partir da técnica de grupo focal, foram submetidos à análise de conteúdo temática, conforme a proposta operativa. Resultados: foram apresentados os cuidados desenvolvidos e compartilhados durante os diferentes ciclos de vida da mulher quilombola. A menarca, gravidez, parto, puerpério e a menopausa foram evidenciados como processos que demandam ações específicas e são realizadas a partir dos recursos existentes no contexto familiar e comunitário. Conclusões: as práticas de cuidados foram construídas a partir dos valores historicamente presentes no universo cultural desta comunidade quilombola. Elas representam ações repassadas intergeracionalmente entre as mulheres, as quais são representadas como os principais cuidadores dentro do contexto domiciliar e familiar, mas também entre os indivíduos que são cuidados por elas.

Aim: to investigate how sociocultural care practices were built among women in a quilombola community. Method: qualitative, descriptive, anthropological research, developed with quilombola women. The data, produced from the focus group technique, were submitted to thematic content analysis, according to the operative proposal. Results: the care developed and shared during the different life cycles of quilombola women were presented. Menarche, pregnancy, childbirth, the puerperium and menopause were evidenced as processes that demand specific actions and are made from the existing resources in the family and community context. Conclusions: the care practices were built from the historically values present in the cultural universe of this quilombola community. They represent actions passed on intergenerationally among women, who are represented as the main caregivers within the home and family context, but also among the individuals who are cared for by them.

Objetivo: investigar cómo eran las prácticas de atención construidos socioculturalmente entre las mujeres de la comunidad quilombola. Método: investigación cualitativa, descriptiva, antropológica, desarrollada con las mujeres quilombolas. Los datos, producidos a partir de la técnica del grupo focal, fueron sometidos a análisis de contenido temático, de acuerdo con la propuesta operativa. Resultados: han sido presentados los cuidados desarrollados y compartidos durante los diferentes ciclos de vida de las mujeres quilombolas. La menarquia, el embarazo, el parto, el puerperio y la menopausia se evidenciaron como procesos que demandan acciones específicas y se realizan con los recursos existentes en el contexto familiar y comunitario. Conclusiones: las prácticas de cuidados fueron construidas a partir de los valores históricamente presentes en el universo cultural de esta comunidad quilombola. Representan acciones transmitidas intergeneracionalmente entre las mujeres, que son representadas como las principales cuidadoras en el contexto de la casa y familiar, pero también entre las personas que son atendidas por ellas.

Intrinsically Disordered Linkers Impart Processivity on Enzymes by Spatial Confinement of Binding Domains.

(1) Background: Processivity is common among enzymes and mechanochemical motors that synthesize, degrade, modify or move along polymeric substrates, such as DNA, RNA, polysaccharides or proteins. Processive enzymes can make multiple rounds of modification without releasing the substrate/partner, making their operation extremely effective and economical. The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors. Processivity may also result from the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker. (2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner. (3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity. We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size. (4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.

[Adherence to adjuvant hormonal therapy in patients with breast cancer]. / Adhesión a la hormonoterapia adyuvante en pacientes con cáncer de mama.

BACKGROUND: Adherence to hormonal therapy (HT) treatment is a complex and multifaceted issue that can determine variations in response to treatment. However, it is little known about it in routine clinical practice. OBJECTIVE: To assess adherence to HT from 1 to 5 years of 190 patients treated at the Hospital de Clínicas (in Montevideo, Uruguay), and to identify factors for the interruption of therapy. MATERIAL AND METHODS: 190 patients treated with HT due to S I-III breast cancer were included from 2002 to 2012. The Kaplan Meier method was used to assess the proportion of patients who discontinued HT, and the univariate analysis with log-rank test was used to identify factors leading to its interruption. RESULTS: Out of 190 patients enrolled in the study, 95.3, 87.9, 80.6, 76.4, and 69.5% were still complying with their HT by the first, second, third, fourth and fifth year, respectively. Therapy continuity was greater in patients who received HT combined with tamoxifen and aromatase inhibitors vs. those who received a single drug (p = 0.017). CONCLUSION: This real-life evaluation showed that HT adherence was reduced by 30.5% at 5 years, despite that there is a well-known benefit of this treatment on overall survival (OS), that it is well-tolerated, and provided for free. In view of the significant impact that HT interruption may have on OS, further investigation is required to determine what cause patients to discontinue their HT, in order to guide our efforts and enable us to increase and optimize adherence.

INTRODUCCIÓN: la adhesión al tratamiento con hormonoterapia (HT) es un tema complejo y polifacético que puede determinar variantes en la respuesta al tratamiento. Sin embargo, se sabe poco acerca de la misma en la práctica clínica habitual. OBJETIVO: evaluar la adherencia a HT de uno a cinco años de 190 pacientes tratadas en el Hospital de Clínicas (de Montevideo, Uruguay) e identificar factores de interrupción de la terapia. MATERIAL Y MÉTODOS: se incluyeron, de 2002 a 2012, 190 pacientes tratadas con HT por cáncer de mama E I-III. Se utilizó el método de Kaplan Meier para valorar la proporción de pacientes que abandonó la HT y el análisis univariado con prueba de log-rank para identificar los factores que podrían influir en su interrupción. RESULTADOS: de las 190 pacientes incluidas, las proporciones de quienes mantuvieron adhesión a la HT, desde el primero hasta el quinto año, fueron sucesivamente de 95.3, 87.9, 80.6, 76.4 y 69.5%. Las pacientes que recibieron HT combinada con tamoxifeno e inhibidores de la aromatasa tuvieron mayor continuidad en el tratamiento respecto de aquellas que recibieron una única droga (p = 0.017). CONCLUSIÓN: evaluamos la adhesión a la HT en la vida real y se redujo un 30.5% en cinco años, a pesar de su conocido beneficio en sobrevida global (SVG), de ser un tratamiento bien tolerado y brindado en forma gratuita. Se deben investigar los motivos de su interrupción, a fin de optimizar su adhesión y ahondar en los esfuerzos para aumentar su cumplimiento, dado el impacto que puede tener en la SVG.

Impacto en la calidad de vida a consecuencia de la mortalidad de dientes permanentes en usuarios de las unidades comunitarias de salud familiar de los municipios de Nuevo Cuscatlán y Chinameca en el año 2018 / Impact on the quality of life as a consequence of the mortality of permanent teeth in users of the community family health units of the municipalities of Nuevo Cuscatlán and Chinameca in 2018

Objetivo: Conocer el impacto en la calidad de vida a consecuencia de la mortalidad de dientes permanentes en los usuarios de las Unidades Comunitarias de Salud Familiar de los municipios de Nuevo Cuscatlán y Chinameca en el año 2018. Metodología: Estudio descriptivo, observacional y transversal de asociación de variables, 288 sujetos entre 15 y +60 años de muestra, partes iguales por sexo; se utilizó cédula de entrevista y guía de observación para registrar las variables en estudio. Vaciado y análisis de datos con SPSS v.25. Resultados: Promedio general de mortalidad dental es 5, alteraciones clínicas y funcionales principalmente asociadas: ruidos articulares 59.7%, mesializaciones 42.7%; los pacientes con pérdida >9 presentaron más incidencia de alteraciones; promedio global del OIDP ubicado en efecto muy ligero 23.29±3.35; existe asociación entre sexo e impacto en calidad de vida p=0.027; la mortalidad dental influye en la de calidad de vida, en efecto muy ligero p=0.000; existe asociación entre mortalidad de dientes y lugar de pérdida p=0.000, mayor frecuencia en zona posteroinferior; la prótesis parcial removible fue la de mayor escoge para la rehabilitación bucal en la población. Conclusiones: La mortalidad de dientes incrementa según la edad de la población, independientemente del sexo; la actividad con mayor frecuencia y gravedad de impacto en calidad de vida fue comer y disfrutar los alimentos; existe asociación entre impacto en la calidad de vida y sexo, entre mortalidad dental y nivel de calidad de vida el efecto fue muy ligero.

Objective: To know the impact on quality of life (QoL) as consequence of the permanent teeth mortality on patients in Family Health Community Units of Nuevo Cuscatlán and Chinameca during 2018. Materials and methods: This is a descriptive, observational and cross-sectional research of variables association, the sample was 288 patients between ages of 15 and+60, equal parts per sex, the data was obtained through an interview and an observation guide, to analyze and interpret the collected data the SPSS version 25 was used. Results: Global average of tooth loss in this population is 5, the clinical and functional changes mainly associated are presence of temporomandibular disorders 59.7% and mesial rotation 42.7%, the patients who have lost less than 9 teeth presented higher incidence of changes, the global OIDP average score 23.29±3.35 was consider very light impact, it exists association between sex and impact of quality of life p=0.027. Teeth mortality influences the level of quality of life, however with a very light effect p=0.000; there is association between tooth loss and localization p=0.000, higher frequency in the posterior and lower jaw; big part of the sample doesn't wear prosthesis and the ones that uses, was removable partial denture. Conclusion: Tooth mortality increases with age, independent of sex, the activity that reported a higher frequency and severity on impact of quality of life was eating and enjoying the meals; it exists association between impact on quality of life and sex; exists association between tooth mortality and QoL, however, the effect was classified as very light.