LATS1 controls CTCF chromatin occupancy and hormonal response of 3D-grown breast cancer cells.

The cancer epigenome has been studied in cells cultured in two-dimensional (2D) monolayers, but recent studies highlight the impact of the extracellular matrix and the three-dimensional (3D) environment on multiple cellular functions. Here, we report the physical, biochemical, and genomic differences between T47D breast cancer cells cultured in 2D and as 3D spheroids. Cells within 3D spheroids exhibit a rounder nucleus with less accessible, more compacted chromatin, as well as altered expression of ~2000 genes, the majority of which become repressed. Hi-C analysis reveals that cells in 3D are enriched for regions belonging to the B compartment, have decreased chromatin-bound CTCF and increased fusion of topologically associating domains (TADs). Upregulation of the Hippo pathway in 3D spheroids results in the activation of the LATS1 kinase, which promotes phosphorylation and displacement of CTCF from DNA, thereby likely causing the observed TAD fusions. 3D cells show higher chromatin binding of progesterone receptor (PR), leading to an increase in the number of hormone-regulated genes. This effect is in part mediated by LATS1 activation, which favors cytoplasmic retention of YAP and CTCF removal.

The efficacy and safety of Emblica officinalis aqueous fruit extract among adult patients with dyslipidemia: A systematic review and meta-analysis

Background@#Flavonoids from Emblica officinalis effectively reduced serum and tissue lipid levels through their inhibitory effect on the hepatic β-hydroxy-β-methylglutaryl coenzyme A reductase activity. This study aimed to determine the efficacy and safety of E. officinalis extract in adults with dyslipidemia.@*Methods@#We searched the following electronic databases: MEDLINE (PubMed), MEDLINE (Ovid), Google Scholar, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science, and ClinicalTrials.gov from inception until January 31, 2022. Two reviewers independently screened the abstracts, reviewed full-text papers, and critically appraised the quality of included studies. Meta-analysis was performed using the random-effects model. Our primary outcomes were total cholesterol, LDL-C, serum triglycerides, and HDL-C levels, while secondary outcomes included adverse events.@*Results@#A total of four randomized trials (N = 227) were included in the final analysis. There were statistically significant decreases in total cholesterol levels (SMD = -21.23 mg/dL, 95% CI: -34.22, -8.25; P = 0.001) and LDL-C levels (SMD = -25.12 mg/dL, 95% CI: -40.24, -10.00; P = 0.001) and significant increase in HDL-C levels (SMD = 4.74 mg/dL, 95% CI: 0.40, 9.07; P = 0.03) after 12 weeks of intervention favoring the use of the Emblica extract over placebo. However, there were no statistically significant difference in the serum triglycerides levels following 12 weeks of treatment (SMD = -22.28 mg/dL, 95% CI: -53.33, 8.76; P = 0.16). There was high heterogeneity noted across all outcomes: total cholesterol (P = 0.01, I2 = 72%), LDL-C (P = 0.0004, I2 = 83%), HDL-C (P < 0.00001, I2 = 91%) and serum triglycerides (P < 0.00001, I2 = 93 %). The intervention was well tolerated and adverse events reported in the three of four studies were all mild: dyspepsia (7 events – treatment), mild diarrhea (3 events – placebo), fever (1 event – placebo), headache (1 event – placebo).@*Conclusion@#Compared to placebo, Emblica officinalis fruit extract resulted in lower total cholesterol and LDL-C levels and increased HDL-C levels but with no effect on serum triglyceride levels based on low certainty of evidence. Trials with a larger sample size that directly compare E. officinalis extract to statins, preferably local data, are needed to support its use in patients with dyslipidemia further.

Exophytic and fungating papillary thyroid carcinoma: A rare and complex presentation of a well-differentiated malignancy

@#Papillary thyroid carcinoma is the most common well-differentiated thyroid malignancy accounting for more than 80 to 90% of all thyroid tumors. It has an overall excellent prognosis owing to advances in screening via imaging and ultrasound-guided fine-needle aspiration biopsy, which have facilitated early detection, diagnosis, and surgical treatment followed by adjuvant radioactive iodine therapy. Exceptionally rare cases of papillary thyroid tumors may present with enormous growth due to delayed consultation and, thus, late diagnosis, posing a challenge to definitive management, quality of life, overall survival, and prognosis. We report a case of a 35-year-old woman who presented with a 4-year history of a bleeding exophytic and fungating anterior neck mass. Computed tomography showed a fungating mass arising from the left thyroid lobe that measured 14.1 x 14.0 x 11.1 cm with areas of necrosis and hemorrhage, left internal jugular vein thrombus formation, and compression of the left internal carotid artery. The mass causes a displacement of the trachea to the right side and multiple bilateral cervical lymphadenopathies. The patient was fully aware, and she consented to undergo wide excision, total thyroidectomy, neck dissection, and pectoralis major muscle flap reconstruction. However, she went into arrest intraoperatively attributed to massive pulmonary embolism. Papillary thyroid cancer is well known for its excellent prognosis. However, outcomes may not be favorable and can even be fatal in advanced and extensive cases. Although fungating papillary cancers are rare, they remain more common in the developing countries, where early detection and access to healthcare remains limited. They also represent a big challenge to surgeons. Even if the outcome was not good, we opted to report this case as there were many learning points. If only patients with good and excellent outcomes are reported in the literature, it will overestimate the treatment success of these complex cases.

Choosing the right partner in hormone-dependent gene regulation: Glucocorticoid and progesterone receptors crosstalk in breast cancer cells.

Steroid hormone receptors (SHRs) belong to a large family of ligand-activated nuclear receptors that share certain characteristics and possess others that make them unique. It was thought for many years that the specificity of hormone response lay in the ligand. Although this may be true for pure agonists, the natural ligands as progesterone, corticosterone and cortisol present a broader effect by simultaneous activation of several SHRs. Moreover, SHRs share structural and functional characteristics that range from similarities between ligand-binding pockets to recognition of specific DNA sequences. These properties are clearly evident in progesterone (PR) and glucocorticoid receptors (GR); however, the biological responses triggered by each receptor in the presence of its ligand are different, and in some cases, even opposite. Thus, what confers the specificity of response to a given receptor is a long-standing topic of discussion that has not yet been unveiled. The levels of expression of each receptor, the differential interaction with coregulators, the chromatin accessibility as well as the DNA sequence of the target regions in the genome, are reliable sources of variability in hormone action that could explain the results obtained so far. Yet, to add further complexity to this scenario, it has been described that receptors can form heterocomplexes which can either compromise or potentiate the respective hormone-activated pathways with its possible impact on the pathological condition. In the present review, we summarized the state of the art of the functional cross-talk between PR and GR in breast cancer cells and we also discussed new paradigms of specificity in hormone action.

Understanding Parental Ethnotheories and Practices About Healthy Eating: Exploring the Developmental Niche of Preschoolers.

PURPOSE: To understand parental ethnotheories (ie, belief systems) and practices about preschoolers' healthy eating guided by the developmental niche framework. DESIGN: Qualitative hermeneutic phenomenology. SETTING: Home. PARTICIPANTS: Participants were 20 parents of preschool-age children ages 3 to 5 years, recruited from a quantitative investigation. A majority of the participants were white, female, married, well educated, and working full time. METHODS: Participants who completed the quantitative survey were asked to provide their contact information if they were willing to be interviewed. From the pool of participants who expressed their willingness to participate in the interviews, 20 participants were selected using a random number generator. In-person semistructured interviews were conducted until data saturation (n = 20). Thematic analysis was performed. RESULTS: Three themes and 6 subthemes emerged: theme 1-parental ethnotheories about healthy eating included subthemes of knowledge about healthy eating, motivations to promote healthy child development through healthy eating, and sources of knowledge about healthy eating (eg, doctors, social media, government guidelines, positive family-of-origin experiences); theme 2-parental ethnotheories that supported organization of children's physical and social settings included structured mealtime routines and food socialization influences (eg, grandparents, siblings, and childcare programs); and theme 3-parental ethnotheories that supported children's learning about healthy eating included parent-child engagement, communication, and encouragement in food-related activities (eg, meal preparation, visiting farmer's market, grocery shopping, gardening, cooking, baking). CONCLUSION: Findings advance the literature on parental practices about healthy eating. Parental ethnotheories (eg, beliefs, motivations, knowledge, and skills) matter. Developmental niche of preschoolers (ie, physical and social settings, childrearing practices, and parental ethnotheories) constitutes an interactive system in which ethnotheories serve as guides to parental practices. Fostering nutrition education and parent-child engagement, communication, and encouragement in food-related activities are recommended to promote children's healthy eating in daily routines.

Sleep habits in infants: the role of maternal education.

OBJECTIVE: Sleep disturbances are frequent in infants. Early development of sleep routines has a positive effect on sleep quality. The objective of this study was to assess the impact of maternal education on the development of infants' sleep habits (SHs). METHODS: This was an experimental, longitudinal study. Postnatal mothers were allocated into two groups: to receive (intervention group, IG), or not receive (control group, CG) information on sleep hygiene. Individual 15-min sessions were provided and a leaflet was handed to the IG. A questionnaire on infants' SHs was applied by telephone/e-mail at 1, 2, 4, and 6 months of age. RESULTS: At least three questionnaires were answered by 314 mothers. Results were adjusted for maternal age, education, and race. In the IG, infants acquired more independent sleep habits, an effect still present at six months; slept more frequently in their own beds; adjusted odds ratio (ORadj) 3.8, 95% confidence interval (CI) (1.1-13.5); fell asleep more frequently alone (ORadj, 4.29; 95% CI, 2.4-7.6); fell asleep more frequently in their own beds (ORadj, 6.1; 95% CI, 3.5-10.6) and needed less breast/bottle feeding to fall asleep (ORadj, 2.68; 95% CI, 1.5-4.6). The autonomy was greater in IG infants after night awakenings; also until six months they went back to sleep more frequently alone (ORadj, 3.88; 95% CI, 2-7.5) and needed less breast/bottle feeding (ORadj, 2.35; 95% CI, 1.3-4.3). No differences were found regarding the need for light, television or other routines to fall asleep or after night awakenings. CONCLUSION: Maternal education is positively associated with the adoption of autonomous SHs in infants. Early maternal education is an adequate prevention strategy to be considered in neonatal care.

Facilitators and barriers to students' learning in an obesity prevention graduate program.

Childhood obesity is a major public health concern with underpinnings at the individual, family, community and societal levels. The Transdisciplinary Childhood Obesity Prevention Graduate Certificate Program (TOP) is an innovative graduate-level certificate program developed to train professionals to understand and address obesity from multiple perspectives using an interprofessional education (IPE) approach. Currently, there is limited knowledge on what promotes or hinders learning in IPE approaches dealing with obesity prevention. The goal of this report is to address this gap by describing facilitators and barriers to learning in a graduate-level training program. Using a qualitative research design, semi-structured interviews were collected from 23 professional students, as part of a larger program evaluation project for TOP. Thematic analysis revealed the challenges and strengths of the program that relate specifically to: its interprofessional approach, its structure, and its activities. Interprofessional exchanges were reported to expand students' learning, but adequate interprofessional representation must be maintained, and the complexity of interprofessional collaborations must also be well-coordinated. Standardising the program structure and courses for consistency across professions, and clear communication are critical to program success. Findings add to the existing literature on what promotes effective learning in a professional obesity prevention program using an IPE approach.

Validation of deformable image registration algorithms on CT images of ex vivo porcine bladders with fiducial markers.

PURPOSE: The spatial accuracy of deformable image registration (DIR) is important in the implementation of image guided adaptive radiotherapy techniques for cancer in the pelvic region. Validation of algorithms is best performed on phantoms with fiducial markers undergoing controlled large deformations. Excised porcine bladders, exhibiting similar filling and voiding behavior as human bladders, provide such an environment. The aim of this study was to determine the spatial accuracy of different DIR algorithms on CT images of ex vivo porcine bladders with radiopaque fiducial markers applied to the outer surface, for a range of bladder volumes, using various accuracy metrics. METHODS: Five excised porcine bladders with a grid of 30-40 radiopaque fiducial markers attached to the outer wall were suspended inside a water-filled phantom. The bladder was filled with a controlled amount of water with added contrast medium for a range of filling volumes (100-400 ml in steps of 50 ml) using a luer lock syringe, and CT scans were acquired at each filling volume. DIR was performed for each data set, with the 100 ml bladder as the reference image. Six intensity-based algorithms (optical flow or demons-based) implemented in theMATLAB platform DIRART, a b-spline algorithm implemented in the commercial software package VelocityAI, and a structure-based algorithm (Symmetric Thin Plate Spline Robust Point Matching) were validated, using adequate parameter settings according to values previously published. The resulting deformation vector field from each registration was applied to the contoured bladder structures and to the marker coordinates for spatial error calculation. The quality of the algorithms was assessed by comparing the different error metrics across the different algorithms, and by comparing the effect of deformation magnitude (bladder volume difference) per algorithm, using the Independent Samples Kruskal-Wallis test. RESULTS: The authors found good structure accuracy without dependency on bladder volume difference for all but one algorithm, and with the best result for the structure-based algorithm. Spatial accuracy as assessed from marker errors was disappointing for all algorithms, especially for large volume differences, implying that the deformations described by the registration did not represent anatomically correct deformations. The structure-based algorithm performed the best in terms of marker error for the large volume difference (100-400 ml). In general, for the small volume difference (100-150 ml) the algorithms performed relatively similarly. The structure-based algorithm exhibited the best balance in performance between small and large volume differences, and among the intensity-based algorithms, the algorithm implemented in VelocityAI exhibited the best balance. CONCLUSIONS: Validation of multiple DIR algorithms on a novel physiological bladder phantom revealed that the structure accuracy was good for most algorithms, but that the spatial accuracy as assessed from markers was low for all algorithms, especially for large deformations. Hence, many of the available algorithms exhibit sufficient accuracy for contour propagation purposes, but possibly not for accurate dose accumulation.

Grado de conocimientos y actitudes de la enfermería de la Comunidad Autónoma de Madrid (cam) ante el dolor: diplomados en enfermería y profesionales / No disponible

El dolor se ha convertido en el quinto signo vital (1-3) y es hoy día un tema crítico en la atención del paciente. El tratamiento eficaz del mismo sigue siendo uno de los problemas más importantes y urgentes del sistema de asistencia sanitaria de los países desarrollados de todo el mundo. Si bien el dolor en los pacientes es un tema muy en boga actualmente, sin embargo, lo que es poco cuestionado es la formación de los futuros profesionales de Enfermería en el cuidado de dichos pacientes. El estudio y el tratamiento del dolor deberían ser inculcados en los estudiantes de Enfermería dentro de su formación, tanto teórica como práctica. Es muy importante la labor que asumen también los docentes en el tema. El reto para la profesión de Enfermería consistiría en este terreno en que organice, estructure y apoye un programa consistente en la activación de programas docentes para estudiantes y enfermeros en ejercicio. Para iniciar nuestro trabajo de investigación realizamos un análisis por una parte, de los actuales programas curriculares de las distintas escuelas de enfermería de la CAM, con asignaturas con contenidos en dolor, analizándose la similitud o no entre ellos, los epígrafes tratados, etc., todo ello comparado con el esbozo curricular que la IASP (International Association of Study of Pain) propuso para los estudios de enfermería; y por otra, se describen los conocimientos y las actitudes de ambos grupos en enfermería ante el dolor, tanto profesionales como estudiantes de enfermería. Para observar el grado de conocimientos y actitudes ante el dolor de ambos grupos, se introdujo como herramienta el NKAS-RP (Nurses' Knowledge and attitudes Survey Regarding Pain) (4). El grupo de trabajo se propuso, por tanto, tres objetivos generales: el primero, descripción de los temarios de las asignaturas de la carrera de enfermería con contenidos en dolor, y el 2.º y 3.º objetivos, definir los conocimientos y las actitudes ante el dolor de los estudiantes de enfermería y de los profesionales enfermeros de la CAM. Se trata de un estudio descriptivo, observacional, aleatorio y multicéntrico, que analiza los conocimientos actuales, así como las actitudes del grupo de enfermería, tanto entre estudiantes (futuros diplomados en enfermería) como entre profesionales. Se llevó a cabo entre los años 2008 al 2010, utilizándose para dar a conocer los resultados del mismo el paquete estadístico SPSS versión 17.0. Como resultados, se obtuvieron, al igual que en estudios previos, a nivel mundial, unos pobres conocimientos en dolor y unas malas actitudes ante dicho síntoma. Se propone para mejorarlos, en el caso de los estudiantes, cambios en los programas curriculares de la diplomatura (futuro grado) de enfermería, y en el caso de los profesionales, formación continuada, así como actualización de conocimientos en dicho tema (AU)

The pain has become the fifth vital sign and is now a critical issue in patient care. Effective treatment of it is still one of the most important and urgent health care system in developed countries worldwide. While pain in patients is a very in vogue these days, however, which is unchallenged is the education of future nursing professionals in the care of such patients. The study and treatment of pain should be instilled in nursing students in their training, both theoretical and practical. The work is very important that teachers also take on the subject. The challenge for the nursing profession in this field would you organize, structure and support a program involving the activation of educational programs for students and practicing nurses. To start our research we made an analysis on the one hand, the current curricula of different schools of nursing in the CAM, with subjects with pain content, analyzing the similarity or not between them, the treated sections, etc. all this curriculum outline compared to the IASP (International Association of Study of Pain) proposed for nursing studies and, secondly, we describe the knowledge and attitudes of both groups in nursing to pain, both professional and qualified nurses. To observe the degree of knowledge and attitudes towards pain in both groups, was introduced as a tool the NKAS-RP (Nurses’ Knowledge and Attitudes Survey Regarding Pain). The working group is proposed, therefore, three general objectives: The first description of the curricula of the courses in the career of nursing content in pain, and el2 and 3 goals, define the knowledge and attitudes to pain nursing students and nurses of the CAM. This is a descriptive, observational, multicenter, randomized, which analyzes the current knowledge and attitudes of the nursing staff, both among students (future graduates in nursing) and among professionals. Was carried out between 2008 and 2010, used to publicize the results of the statistical package SPSS version 17.0. As results were obtained, as in previous studies, worldwide, a poor knowledge of pain and a bad attitude before that symptom. It is proposed to improve: in the case of students, changes in the curriculum of the Diploma (future degree) nurses, and in the case of professionals, continuing education and refresher courses in that subject (AU)

Effect of batch and fed-batch growth modes on biofilm formation by Listeria monocytogenes at different temperatures.

The influence of Listeria monocytogenes (L. monocytogenes) biofilm formation feeding conditions (batch and fed-batch) at different temperatures on biofilm biomass and activity was determined. Biofilm biomass and cellular metabolic activity were assessed by Crystal Violet (CV) staining and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) colorimetric method, respectively. Live/Dead staining was also performed in order to get microscopic visualization of the different biofilms. Results revealed that at refrigeration temperature (4 degrees C) a higher amount of biofilm was produced when batch conditions were applied, while at higher temperatures the fed-batch feeding condition was the most effective on biofilm formation. Moreover, independently of the temperature used, biofilms formed under fed-batch conditions were metabolically more active than those formed in batch mode. In conclusion, this work shows that different growth modes significantly influence L. monocytogenes biofilm formation on abiotic surfaces as well as the metabolic activity of cells within biofilms.

Religiosity, values, and horizontal and vertical individualism-collectivism: a study of Turkey, the United States, and the Philippines.

The authors examined the links between two dimensions that have been useful in understanding cross-cultural differences and similarities, namely, individualism-collectivism (I-C) and value orientations. The authors examined the relations and parallels between the two variables by directly relating them and examining the patterns of relations that both have with a third variable, religiosity. Participants were 475 college students from the Philippines, the United States, and Turkey who responded to measures of horizontal and vertical I-C, value orientations, and religiosity. The authors found partial support for the parallels between I-C and value types, particularly for collectivism and conservative values. Moreover, religiosity was associated positively with conservative values and collectivism, across all three cultures. The authors found individualism to also relate to openness-to-change values, though the patterns were not as consistent as those that they found between collectivism and conservation. Differences and similarities emerged in links of I-C-values to religiosity across the three samples.

Fullerenes as a new class of radioprotectors.

PURPOSE: To evaluate the radioprotective activity of C3, a regioisomer of water-soluble carboxyfullerene and a potent free radical scavenger, on both normal and tumour cells. MATERIALS AND METHODS: The murine committed bone-marrow stem cells for both granulocytes and monocytes (GM-CFC) were used to represent normal cells. For tumour cells, murine Ehrlich ascites tumour cells grown in regular tissue culture (EAT-T) and in the peritoneal cavity of CD1 mice (EAT-PC) and human HeLa cells were used. Cells were preexposed to varying concentrations (1-100 microg/ml) of C3 at 37 degrees C for 30 min before they were irradiated. Clonogenic assays were used to determine survival. The protection factor (PF), defined as the ratio of survival with and without C3, was then determined. RESULTS: C3 protected GM-CFC in a concentration-dependent manner up to 50 microg/ml, and no additional protection was seen at 100 microg/ml. The PF was 1.77 when bone-marrow cells were pre-exposed to 50 microg/ml of C3 before they were irradiated with 2 Gy. The value of PF increased to 2.38 when 4 Gy was used. In sharp contrast, C3 exerted less radioprotective effect on tumour cells. The PF values were 1.07, 1.43 and 1.07 for EAT-T, EAT-PC, and HeLa cells, respectively, when 2 Gy was given in the presence of 50 microg/ml of C3. These values increased to 1.40, 1.75 and 1.27, respectively, when 4Gy was given. The dose-modifying factors at 10% survival were 1.37 and 1.15 for GM-CFC and EAT-PC, respectively. CONCLUSION: C3 exhibits a radioprotective effect on a class of normal haemopoietic progenitor cells. It also protects tumour cells, but to a lesser degree. It appears that C3 and other water-soluble fullerenes have a potential to be a new class of cytoprotectors.