Spontaneous twin anemia-polycythemia sequence from two donors to one recipient in a monochorionic triamniotic pregnancy: Case report and review of the literature.

Monochorionic triamniotic (MCTA) pregnancies present a high number of complications, mainly due to the presence of unbalanced vascular anastomoses, such as twin anemia-polycythemia sequence (TAPS). Previous reported cases related to TAPS are in twin pregnancies or only affect the monochorionic component of dichorionic triamniotic (DCTA) pregnancies. We report an exceptional case, the only one reported as far as we know, of a MCTA pregnancy that developed a TAPS in which the three triplets are implicated, from two donors to one recipient. The pregnancy had been previously sonographically diagnosed as DCTA pregnancy and this could not explain the clinical results. The pathological study of the placenta showed the presence of three monochorionic dividing membranes, a congested area in the recipient parenchyma and two non-congested areas in the donor's parenchyma that confirmed the clinical findings. Pathological study of multiple placentas should always be done because it provides understanding of pregnancy complications.

Reciprocal regulation of amino acid import and epigenetic state through Lat1 and EZH2.

Lat1 (SLC7A5) is an amino acid transporter often required for tumor cell import of essential amino acids (AA) including Methionine (Met). Met is the obligate precursor of S-adenosylmethionine (SAM), the methyl donor utilized by all methyltransferases including the polycomb repressor complex (PRC2)-specific EZH2. Cell populations sorted for surface Lat1 exhibit activated EZH2, enrichment for Met-cycle intermediates, and aggressive tumor growth in mice. In agreement, EZH2 and Lat1 expression are co-regulated in models of cancer cell differentiation and co-expression is observed at the invasive front of human lung tumors. EZH2 knockdown or small-molecule inhibition leads to de-repression of RXRα resulting in reduced Lat1 expression. Our results describe a Lat1-EZH2 positive feedback loop illustrated by AA depletion or Lat1 knockdown resulting in SAM reduction and concomitant reduction in EZH2 activity. shRNA-mediated knockdown of Lat1 results in tumor growth inhibition and points to Lat1 as a potential therapeutic target.

Ceramic/metal biocidal nanocomposites for bone-related applications.

Hydroxyapatite/silver nanocomposites have been designed and synthesized as an engineering material for biomedical applications. The hydroxyapatite matrix was synthesized by a sol-gel method and, subsequently, the Ag nanoparticles were deposited by heterogeneous precipitation followed by two different reduction routes: thermal or chemical. Both sets were studied and compared and, in all cases, the metal nanoparticles appear perfectly isolated and attached to the surface of the hydroxyapatite. The average metal particle size is below 10 nm, allowing an important contact surface between silver and the microorganisms. The antimicrobial behavior against common bacteria showed a high effectiveness, well above the commercial level, as well as against yeast, in the case of the chemically reduced sample. Due to the nanocomposite microstructure, only a negligible portion of metal was released to the lixiviated liquid after the biocide tests, minimizing the risk of toxicity. These nanocomposites offer a solution to the infections on the surface of implants, one of the main problems in reaching a suitable level of osseointegration.

Association of Age and Temperamental Traits with Children's Behaviour during Dental Treatment.

During paediatric dental treatment, cooperation by children is essential, and temperament can determine their behaviour style. This study aimed to associate temperamental traits and age with behaviour during paediatric dental treatment. This was an observational and cross-sectional study of patients aged 3-10 years. To determine the temperamental traits, an Emotionality Activity and Sociability Temperament Survey (EAS) was performed with the children's parents. The type of behaviour was determined with Frankl's criteria. The total scores for temperamental traits, means, and standard deviations were obtained. The chi-squared test, one-way ANOVA and Student's t-test were applied. A total of 140 patients, who were 5 ± 2.1 years old, participated in the study. Age was determinant for negative behaviour, with a greater frequency in children ≤5 years old (p < 0.05), and a significant negative correlation between age and behaviour (rho = -0.245, p = 0.001). Patients with higher emotionality and activity presented negative and definitely negative behaviours more frequently (p < 0.01). The values for sociability and shyness were similar for positive or negative behaviours. In conclusion, the temperamental traits of emotionality and activity were more frequent in children with disruptive behaviours; therefore, conducting a survey on temperamental traits can be useful for planning behavioural approaches in paediatric dentistry.

Photoelasticity for Stress Concentration Analysis in Dentistry and Medicine.

Complex stresses are created or applied as part of medical and dental treatments, which are linked to the achievement of treatment goals and favorable prognosis. Photoelasticity is an optical technique that can help observe and understand biomechanics, which is essential for planning, evaluation and treatment in health professions. The objective of this project was to review the existing information on the use of photoelasticity in medicine and dentistry and determine their purpose, the areas or treatments for which it was used, models used as well as to identify areas of opportunity for the application of the technique and the generation of new models. A literature review was carried out to identify publications in dentistry and medicine in which photoelasticity was used as an experimental method. The databases used were: Sciencedirect, PubMed, Scopus, Ovid, Springer, EBSCO, Wiley, Lilacs, Medigraphic Artemisa and SciELO. Duplicate and incomplete articles were eliminated, obtaining 84 articles published between 2000 and 2019 for analysis. In dentistry, ten subdisciplines were found in which photoelasticity was used; those related to implants for fixed prostheses were the most abundant. In medicine, orthopedic research predominates; and its application is not limited to hard tissues. No reports were found on the use of photoelastic models as a teaching aid in either medicine or dentistry. Photoelasticity has been widely used in the context of research where it has limitations due to the characteristics of the results provided by the technique, there is no evidence of use in the health area to exploit its application in learning biomechanics; on the other hand there is little development in models that faithfully represent the anatomy and characteristics of the different tissues of the human body, which opens the opportunity to take up the qualitative results offered by the technique to transpolate it to an application and clinical learning.

[Photoelastic models applied to dental restorations]. / Modelos fotoelásticos aplicados a la restauración dental.

Objective: To improve the understanding of the changes generated by restorative procedures through photoelastic models. Dental reconstruction should be based on principles of occlusion in order not to cause premature contact points during preparation and restoration procedures that can lead to disorders such as occlusal trauma, temporo-mandibullary joint dysfunction, or fractures. This paper presents a didactic method to objectively visualize occlusal loads and their distribution. Materials and methods: Photoelastic models of teeth and maxillary segments were made to visualize the effects of dental preparations and restorations, as well as the wear of premature contact points. Results: The direction, intensity and distribution of stresses in the crown and bone support were analyzed by photoelasticity. Conclusions: The technique allows visualization of how the structures are affected from the cavity preparation, the different stresses with diamond or carbide burs, in addition to observing how a premature contact point not only affects the organ that contains it but also the surrounding structures.

Comparison of the biometric values obtained by two different A-mode ultrasound devices (Eye Cubed vs. PalmScan): a transversal, descriptive, and comparative study.

BACKGROUND: To assess the reliability of the measurements obtained with the PalmScan, when compared with another standardized A-mode ultrasound device, and assess the consistency and correlation between the two methods. METHODS: Transversal, descriptive, and comparative study. We recorded the axial length (AL), anterior chamber depth (ACD) and lens thickness (LT) obtained with two A-mode ultrasounds (PalmScan A2000 and Eye Cubed) using an immersion technique. We compared the measurements with a two-sample t-test. Agreement between the two devices was assessed with Bland-Altman plots and 95% limits of agreement. RESULTS: 70 eyes of 70 patients were enrolled in this study. The measurements with the Eye Cubed of AL and ACD were shorter than the measurements taken by the PalmScan. The differences were not statistically significant regarding AL (p < 0.4) but significant regarding ACD (p < 0.001). The highest agreement between the two devices was obtained during LT measurement. The PalmScan measurements were shorter, but not statistically significantly (p < 0.2). CONCLUSIONS: The values of AL and LT, obtained with both devices are not identical, but within the limits of agreement. The agreement is not affected by the magnitude of the ocular dimensions (but only between range of 20 mm to 27 mm of AL and 3.5 mm to 5.7 mm of LT). A correction of about 0.5 D could be considered if an intraocular lens is being calculated. However due to the large variability of the results, the authors recommend discretion in using this conversion factor, and to adjust the power of the intraocular lenses based upon the personal experience of the surgeon.

Synthesis, SAR study and biological evaluation of novel pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as anti-proliferative agents.

Checkpoint deficiency of malignant cells can be exploited in cancer drug discovery. Compounds that selectively kill checkpoint-deficient cells versus checkpoint-proficient cells can be utilized to preferentially target tumor cells, while sparing normal cells. The protein p21(Wafl/Cipl/Sdi1) (hereafter referred to as p21) inhibits progression of the cell cycle by inhibiting the activity of G1 kinases (cyclin D/cdk4 and cyclin E-cdk2) and the G2 kinase (cyclin B/cdkl) in response to DNA damage or abnormal DNA content. The expression of p21 is often low in human cancer cells due to frequent loss of the upstream activator, p53, and is associated with poor prognosis in some cancer patients. Using an isogenic pair of cell lines, HCT116 (p21+/+) and 80S14 (p21-/-), we have disclosed previously a novel series of pyrazolo[1,5-a]pyrimidines that preferentially kill the p21-deficient cells. We will present the synthesis, biological activities and SAR study of a series of pyrazolo[1,5-a]pyrimidines with an optimized phenyl amide moiety at the C-7 position. The mechanism of action of these compounds will also be discussed.

[Ethical Aspects of the Use of Mirena(r) Iud in the Treatment of Heavy Menstrual Bleeding]. / Aspectos Éticos del Uso del Diu Mirena(r) En el Tratamiento de la Hemorragia Menstrual Severa.

The levonorgestrel-releasing intrauterine device known as Mirena IUD(r) (20mcg/24h) is nowadays considered among the leading resources in the treatment of heavy menstrual bleeding. Nonetheless, due to either its effect of prevention of conception and especially to the possibility that it may also have an anti-implantation effect, there is a founded concern on whether its therapeutic use may be ethically licit. This article engages in an exhaustive literature review in order to ascertain the mechanism of action of Mirena(r) IUD, in view of an ethical evaluation of its therapeutic use, keeping in mind those two unwanted effects. According to the most recent bibliography, the modification of the cervical mucus in patients carrying Mirena(r) IUD seems to consistently impede the spermatozoa penetration through the cervix, thus keeping down the probability of conception. Therefore, the likelihood of inducing an embryonic loss that can be ascribed to the device seems to be virtually nil. Given that there are no therapeutic alternatives that respect fertility as they address the pathology once the first-line treatments have failed, the prevention of fertilization effect of Mirena(r) IUD may be judged as ethically acceptable. Moreover one cannot conclude that the embryonic loss that might aggravate the moral evaluation of its use actually takes place.

[Giant gravidarum granuloma of the scalp]. / Granuloma gravidarum gigante en piel cabelluda.

Lobular capillary hemangioma (pyogenic granuloma) has been reported more frequently in the skin (88%) than in the mucous membranes (12%). Granuloma gravidarum is a pyogenic granuloma that develops during pregnancy, often in the oral mucosa. Estrogens apparently increase the inflammatory response of mucous membranes. In this article, we describe the first case of a granuloma gravidarum of the scalp.

Enfermedades musculoesqueléticas y su asociación con el sobrepeso y obesidad en adultos mayores, un estudio transversal / Musculoskeletal diseases and their association with overweight and obesity in older adults, a cross-sectional study

Objetivo: determinar la prevalencia y la asociación de enfermedades musculoesqueléticas con el sobrepeso y obesidad, y las diferencias respecto a edad y sexo. Métodos: el presente estudio es de tipo transversal, descriptivo y analítico, el universo está compuesto por pacientes adultos mayores a 60 años con diagnóstico de enfermedades musculoesqueléticas que acuden a consulta en el periodo de enero a diciembre, del año 2019, en el centro de salud "Villa Oruro", en Tiquipaya, Cochabamba, Bolivia, con un muestreo no probabilístico por conveniencia, la muestra del estudio fue 353 pacientes. Resultados: se evaluó a 353 pacientes mayores a 60 años, 156 hombres y 197 mujeres, con una edad promedio de 71,51 ± 8,45 con índice de masa corporal promedio de 26,68 ± 1,77. Se realizó el análisis estadístico de asociación de variables categóricas, en base a rangos del índice de masa corporal (sobrepeso y obesidad) con las enfermedades musculoesqueléticas. Conclusiones: dentro de la evaluación del sobrepeso y obesidad, y su relación con patologías musculoesqueléticas, la gonartrosis es la más relacionada con la presencia de sobrepeso y obesidad, por lo que se recomienda establecer métodos de educación en la población con hábitos alimenticios y estilos de vida saludables para disminuir la prevalencia de enfermedades musculoesqueléticas asociadas a sobrepeso y obesidad.

Objectives: the aim of this study is to determine the prevalence and association of musculoskeletal diseases with overweight and obesity, and the differences with respect to age and sex. Methods: this type of study is cross-sectional, descriptive and analytical, the universe is composed of adult patients over 60 years of age with a diagnosis of musculoskeletal diseases who come for consultation in the period from January to December, year 2019, of the health center "Villa Oruro", Tiquipaya, Cochabamba, Bolivia, with a non-probabilistic sampling by convenience, the study sample was 353 patients. Results: we evaluated 353 patients over 60 years of age, 156 men and 197 women, with an average age of 71.51 ± 8.45 with an average body mass index of 26.68 ±1.77. Statistical analysis of association of categorical variables, based on body mass index ranges (overweight and obesity) with musculoskeletal diseases, was performed. Conclusions: within the evaluation of overweight and obesity, and their relationship with musculoskeletal pathologies, gonarthrosis is the most related to the presence of overweight and obesity, it is recommended and establish education in the population with healthy eating habits and lifestyles to reduce the prevalence of musculoskeletal diseases associated with overweight and obesity.

Autonomous self-healing structural composites with bio-inspired design.

Strong and tough natural composites such as bone, silk or nacre are often built from stiff blocks bound together using thin interfacial soft layers that can also provide sacrificial bonds for self-repair. Here we show that it is possible exploit this design in order to create self-healing structural composites by using thin supramolecular polymer interfaces between ceramic blocks. We have built model brick-and-mortar structures with ceramic contents above 95 vol% that exhibit strengths of the order of MPa (three orders of magnitude higher than the interfacial polymer) and fracture energies that are two orders of magnitude higher than those of the glass bricks. More importantly, these properties can be fully recovered after fracture without using external stimuli or delivering healing agents. This approach demonstrates a very promising route towards the design of strong, ideal self-healing materials able to self-repair repeatedly without degradation or external stimuli.

Understanding Mechanical Response of Elastomeric Graphene Networks.

Ultra-light porous networks based on nano-carbon materials (such as graphene or carbon nanotubes) have attracted increasing interest owing to their applications in wide fields from bioengineering to electrochemical devices. However, it is often difficult to translate the properties of nanomaterials to bulk three-dimensional networks with a control of their mechanical properties. In this work, we constructed elastomeric graphene porous networks with well-defined structures by freeze casting and thermal reduction, and investigated systematically the effect of key microstructural features. The porous networks made of large reduced graphene oxide flakes (>20 µm) are superelastic and exhibit high energy absorption, showing much enhanced mechanical properties than those with small flakes (<2 µm). A better restoration of the graphitic nature also has a considerable effect. In comparison, microstructural differences, such as the foam architecture or the cell size have smaller or negligible effect on the mechanical response. The recoverability and energy adsorption depend on density with the latter exhibiting a minimum due to the interplay between wall fracture and friction during deformation. These findings suggest that an improvement in the mechanical properties of porous graphene networks significantly depend on the engineering of the graphene flake that controls the property of the cell walls.

24-Gy low-voltage x-ray irradiation with ranibizumab therapy for neovascular AMD: 6-month safety and functional outcomes.

BACKGROUND AND OBJECTIVE: To describe the 6-month safety and preliminary efficacy outcomes of the use of 24-Gy radiation with intravitreal ranibizumab for patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: A single treatment of a non-invasive, externally delivered low-voltage x-ray irradiation at a dose of 24 Gy was administered in one session through three locations in the inferior pars plana in a consecutive series of patients with neo-vascular AMD (treatment naïve and previously treated). Optical coherence tomography (OCT) and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity examinations were performed at 1 week, 1 month, and monthly thereafter with quarterly fluorescein angiography. RESULTS: Nineteen patients completed 6 months of follow-up. There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean baseline ETDRS score was 38.3 ± 19.5 letters. At 6 months, the corresponding ETDRS score was 44.7 ± 16.8 letters. At 6 months, the mean change in visual acuity was 6.4 ± 9.8 ETDRS letters. Patients received an average of 0.4 additional ranibizumab injections following the initial two mandated injections. CONCLUSION: A single treatment of external 24-Gy low-voltage x-ray therapy in conjunction with ranibizumab demonstrated an overall improvement in visual acuity in patients with neovascular AMD at 6 months, with no radiation-related adverse effects.

16-Gy low-voltage x-ray irradiation followed by as-needed ranibizumab therapy for AMD: 6-month outcomes of a "radiation-first" strategy.

BACKGROUND AND OBJECTIVE: To describe the effect of a "radiation-first" combination treatment strategy for neovascular age-related macular degeneration (AMD) with ranibizumab rescue therapy. PATIENTS AND METHODS: Non-invasive, externally delivered low-voltage x-ray irradiation at a dose of 16 Gy was given in a single session through three locations in the inferior pars plana in a consecutive series of patients with neovascular AMD. Ranibizumab was administered according to prospectively determined criteria. RESULTS: Thirteen patients completed a 6-month follow-up. All patients lost 15 or fewer ETDRS letters, 7 gained 0 or more ETDRS letters, and 0 gained more than 15 ETDRS letters. Patients received a total of 15 ranibizumab injections following x-ray irradiation at baseline. Two patients received no ranibizumab injections, seven patients received 1 injection, and four patients received 2 injections. CONCLUSION: Low-voltage x-ray treatment followed by ranibizumab rescue demonstrates an independent visual acuity stabilizing effect for patients with wet AMD.

16-Gy low-voltage x-ray irradiation with ranibizumab therapy for AMD: 6-month safety and functional outcomes.

BACKGROUND AND OBJECTIVE: To describe the 6-month safety and preliminary efficacy outcomes of the use of 16-Gy radiation with intravitreal ranibizumab for patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: A single treatment of a non-invasive, externally delivered low-voltage 16-Gy x-ray irradiation was administered in one session through three locations in the inferior pars plana. Optical coherence tomography (OCT) and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) examinations were performed at 1 week, 1 month, and monthly thereafter, with quarterly fluorescein angiography (FA). After the two initial ranibizumab injections, subsequent injections were administered according to the following criteria: VA decline of 10 ETDRS letters compared with baseline, increase of 100-µm central foveal thickness on OCT compared with baseline, the development of new submacular hemorrhage, and the development of a new area of classic choroidal neovascularization on FA. RESULTS: Twenty-six patients completed a 6-month follow-up. There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean baseline ETDRS score was 46.6 letters (range: 5 to 80; standard deviation [SD]: 21.5). At 6 months, the corresponding ETDRS score was 55.6 letters (range: 25 to 80; SD: 18.9) and the mean change in VA was 9.5 ETDRS letters (SD: 10.3). On responder analysis, 96% lost 15 or fewer ETDRS letters, 81% gained 0 or more ETDRS letters, and 50% gained 15 or more ETDRS letters. Patients received a total of 13 ranibizumab injections following two initial injections. At 6 months, patients received an average of 0.5 additional injections following the initial two mandated injections. CONCLUSION: A single treatment of externally applied, non-invasive 16-Gy low-voltage x-ray therapy in conjunction with ranibizumab demonstrated an overall improvement of VA in patients with neovascular AMD at 6 months with no radiation-related adverse effects.

Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel antiproliferative agents: exploration of core and headpiece structure-activity relationships.

A novel series of antiproliferative agents containing pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides, selective for p21-deficient cells, were identified by high-throughput screening. Exploration of the SAR relationships in the headpiece, core, and tailpiece is described. Strict steric, positional, and electronic requirements were observed, with a clear preference for both core nitrogens, a thienoyl headpiece, and meta substituted tailpiece.

Costa Rican environmental service payments: The use of a financial instrument in participatory forest management.

The core element of the Costa Rican forestry policy is a financial instrument called the environmental service payment. This instrument rewards forest owners for the environmental services (the mitigation of greenhouse gases, the protection of watersheds and scenic beauty, and the development of biodiversity) their forests provide. In this article, the experiences with this new instrument are analyzed by focusing on the way interests are represented and access is granted, the openness of information exchange, whether social learning occurred, and whether decision-making authority is shared. The analysis is based on a survey conducted in the Huetar Norte Region and on in-depth interviews with the major stakeholders. The Costa Rican case indicates that financial instruments can be used to share responsibilities and that stakeholders can successfully cooperate on forest issues. It also shows that such a participatory approach is only promising if certain cultural, economic, organizational, and political conditions are met.

Validation of cyclin D1/CDK4 as an anticancer drug target in MCF-7 breast cancer cells: Effect of regulated overexpression of cyclin D1 and siRNA-mediated inhibition of endogenous cyclin D1 and CDK4 expression.

We have examined the role of cyclin D1 and cyclin-dependent kinase-4 (CDK4) in the cell cycle progression and proliferation of MCF-7 breast cancer cells. Forced expression of cyclin D1 using a tetracycline-regulated expression system, and suppression of endogenous cyclin D1 and CDK4 using small interfering RNA (siRNA) were used to validate this protein complex as a drug target in cancer drug discovery. Overexpression of cyclin D1 increased both phosphorylation of the retinoblastoma gene product (RB) and passage through the G1-S phase transition, resulting in increased proliferation of cells. When cyclin D1 expression was shut off, growth rates fell below those seen in control cell lines transfected with the vector, indicating an increased dependence on this protein for proliferation. Inhibition of endogenous cyclin D1 or CDK4 expression by RNA interference resulted in hypophosphorylation of RB and accumulation of cells in G1. These results support the prevailing view that pharmacological inhibition of cyclin D1/CDK4 complexes is a useful strategy to inhibit the growth of tumors. Furthermore, since MCF-7 cells appear to be dependent on this pathway for their continued proliferation, it is a suitable cell line to test novel cyclin D1/CDK4 inhibitors.

Inhibition of tumor cell proliferation by thieno[2,3-d]pyrimidin-4(1H)-one-based analogs.

On the basis of a screening lead from an assay using a pair of p21 isogenic cell lines (p21-proficient cells and p21-deficient cells) to identify chemoselective agents, a series of novel thieno[2,3-d]pyrimidin-4(1H)-one-based analogs was prepared. Some analogs inhibited the growth of human colon tumor cells.