Biochemical Activity of 17 Cancer-Associated Variants of DNA Polymerase Kappa Predicted by Electrostatic Properties.

DNA damage and repair have been widely studied in relation to cancer and therapeutics. Y-family DNA polymerases can bypass DNA lesions, which may result from external or internal DNA damaging agents, including some chemotherapy agents. Overexpression of the Y-family polymerase human pol kappa can result in tumorigenesis and drug resistance in cancer. This report describes the use of computational tools to predict the effects of single nucleotide polymorphism variants on pol kappa activity. Partial Order Optimum Likelihood (POOL), a machine learning method that uses input features from Theoretical Microscopic Titration Curve Shapes (THEMATICS), was used to identify amino acid residues most likely involved in catalytic activity. The µ4 value, a metric obtained from POOL and THEMATICS that serves as a measure of the degree of coupling between one ionizable amino acid and its neighbors, was then used to identify which protein mutations are likely to impact the biochemical activity. Bioinformatic tools SIFT, PolyPhen-2, and FATHMM predicted most of these variants to be deleterious to function. Along with computational and bioinformatic predictions, we characterized the catalytic activity and stability of 17 cancer-associated DNA pol kappa variants. We identified pol kappa variants R48I, H105Y, G147D, G154E, V177L, R298C, E362V, and R470C as having lower activity relative to wild-type pol kappa; the pol kappa variants T102A, H142Y, R175Q, E210K, Y221C, N330D, N338S, K353T, and L383F were identified as being similar in catalytic efficiency to WT pol kappa. We observed that POOL predictions can be used to predict which variants have decreased activity. Predictions from bioinformatic tools like SIFT, PolyPhen-2, and FATHMM are based on sequence comparisons and therefore are complementary to POOL but are less capable of predicting biochemical activity. These bioinformatic and computational tools can be used to identify SNP variants with deleterious effects and altered biochemical activity from a large data set.

The Cell and Gene Therapy Consortium's Perspective on Harmonizing Data Collection for Patient Enrollment, Therapy Ordering and Scheduling, and Cell Collection.

Established in October 2021, the Cell and Gene Therapy (CGT) Consortium convened with the goal to bring together key CGT stakeholders - manufacturers, treatment centers, regulators, services providers, and ecosystem partners - to gain alignment on process definitions, terminology, challenges, and opportunities for process and data standardization from CGT program start-up and patient enrollment to therapy administration. With the recognition that the number of investigational and commercial cell and gene therapies will scale over the next several years, so will the number of manufacturer-specific processes and solutions (e.g., portals). As a result, this will increase the burden on academic medical centers, community hospitals, standalone clinics, collection facilities, and labs. Healthcare professionals (HCPs) and other industry stakeholders agree that a multiplicity of manufacturer portals with varying data requirements and nomenclature is unsustainable and adds unnecessary complexity - risk, cost, and time - in coordinating patient treatment. Following extensive discussions and multiple stakeholder meetings and interviews, we have developed a manuscript reporting on our activities and conclusions. Through the course of the manuscript, we delineate a framework for defining common principles, terminology, and user experiences for enrolling patients, ordering therapies, and collecting starting material in a standardized way. We also provide substantial background information on opportunities to streamline communications between manufacturing and healthcare organizations from the HCP end-user's perspective.

Radiesse Rescue: A Preliminary Study for a Simple and Effective Technique for the Removal of Calcium Hydroxyapatite-Based Fillers.

BACKGROUND: Radiesse, or calcium hydroxyapatite (CaHA), is a semipermanent, biodegradable injectable filler that provides immediate aesthetic improvement, while also stimulating neocollagenesis for biological effects. The physical properties of CaHA make it difficult, if not impossible, to remove. Unlike some hyaluronic acid-based fillers, CaHA cannot be easily dissolved. OBJECTIVES: The aim of this study was to present a simple and reliable technique for debulking and removing excess CaHA in the event of nodule formation, vascular compression, or overcorrection. METHODS: An 18-gauge needle was used to make an incision near the filler excess. A 1-mm-diameter grater-type microliposuction cannula (Lipocube, Inc.; London, UK) was attached to a 5- to 10-mL syringe under negative pressure. The cannula under syringe suction was used in a back-and-forth reaming motion beginning in the base of the material and gradually moving toward the surface until the desired effect was achieved. Identification of the CaHA can be established and removal confirmed with ultrasound (Clarius, Inc.; Vancouver, BC, Canada) if available. RESULTS: Although nodules, excess material and vascular compression secondary to CaHA are very rare occurrences, 4 patients were treated with excess material and/or nodules. In 1 patient, the prominent cheek filler was reduced and a 1-cm nodule that was palpable in the buccal region was eliminated. In the other 3 other patients, the palpable excess material was easily removed, in 2 at the time of injection and in the third, 6 months later. No patient required repeat treatment or replacement. CONCLUSIONS: This removal technique has been shown to adequately remove excess CaHA filler but is not applicable to inadvertent intravascular injection.

Cosmecéuticos Indispensable para otorrinolaringólogos y cirujanos plásticos faciales / Cosmeceuticals Essential for facial plastic surgeons and otolaryngologists

Objetivos: Definir el término cosmecéutica, presentar los ingredientes activos más comúnmente utilizados, sus indicaciones y ventajas. Evaluar nuestros productos para el cuidado y rejuvenecimiento de la piel, teniendo en cuenta variables como pigmentación, líneas de expresión y ritides finas, hidratación, brillo y envejecimiento. Diseño: Serie de Casos Materiales y métodos: Se realizó un estudio retrospectivo mediante análisis fotográfico ciego de 50 casos de rejuvenecimiento facial usando únicamente cosmecéutica seleccionados al azar durante el periodo Agosto 2015 ­ Julio 2016. Se utilizó un régimen cosmecéutico personalizado incluyendo: limpieza y exfoliación, hidratación, reparación, despigmentantes, antienvejecimiento y fotoprotección, dos veces al día durante 6 meses. Las variables evaluadas mediante una escala semi-cuantitativa de 5 puntos fueron: pigmentación, ritides finas, envejecimiento en general, hidratación, brillo cutáneo y mejoría estética. La prueba no paramétrica de Wilcoxon fue seleccionada para evaluar significancia estadística. Resultados: Las lesiones pigmentadas, las ritides finas y el envejecimiento en general disminuyeron 32.7, 26.3 y 22%, respectivamente. Alcanzando significancia estadística (p<0,05). El brillo y la hidratación mejoraron en 47.5 y 55.3%, respectivamente. Se encontró una mejoría estética del 58%. La escala analógica visual reveló un rejuvenecimiento del 16,5% (p=0,0018). Conclusiones: La incorporación de cosmecéuticos en la práctica de la otorrinolaringología y la cirugía plástica facial mejora la apariencia de los pacientes, rejuvenece la piel y puede contribuir potenciando los resultados posoperatorios.

Objectives: To define cosmeceuticals, introduce common active ingredients, their indications and advantages, and to assess our skin care protocol anti-aging effects, improving dyschromia, wrinkles, hydration and other signs of aging. Design: Case Series Materials and methods: We developed a retrospective photographic analysis of 50 facial rejuvenation patients using our cosmeceuticals. A blind photographic analysis of dyschromia, fine wrinkles, overall aging, skin light reflection, hydration and aesthetic improvement using 5-point grading scales was carried out. The nonparametric Wilcoxon test was selected to evaluate statistical significance. A tailored cosmeceutical regimen including: cleaning and exfoliating, moisturizing, repairing, pigment lightening, anti-aging formulations and photo-protection was applied twice a day for 6 months. Results: Dyschromia, fine wrinkles and overall aging decreased 32.7, 26.3 and 22 percent, respectively. Reaching statistical significance (p<0,05). Luminosity, hydration and overall aesthetic change improved 47.5, 55.3 and 58 percent, respectively. The visual analog aging severity scale revealed a statistically significant 16,5% of rejuvenation (p=0,0018). Conclusions: Incorporating cosmeceuticals in the facial plastic surgery practice can promote a better overall patient experience by rejuvenating the skin, hastening postoperative healing and reducing common postoperative side effects.

Validación de la “Escala multicomponente de fobia al sida” con adolescentes españoles / Multicomponent AIDS Phobia Scale validation with Spanish adolescents

La fobia al sida se caracteriza por un miedo persistente, intenso e irracional a contraer el VIH. Este temor se relaciona con el estigma hacia la infección y la discriminación de las personas afectadas. El objetivo de este estudio es validar la “Escala multicomponente de fobia al sida” (Multicomponent AIDS Phobia Scale, MAPS) con adolescentes españoles y examinar si la estructura del miedo al sida es similar a la encontrada en muestra estadounidense. Participaron 832 estudiantes de secundaria con edades entre 14 y 18 años. Los datos indican una estructura bifactorial de la escala, presentando una fiabilidad compuesta de 0,77. La validez convergente hallada mediante las correlaciones con las puntuaciones en conocimientos sobre el VIH/sida y en actitudes hacia el sida fue adecuada. Las bajas correlaciones entre la MAPS, las puntuaciones en ansiedad por la salud y en ansiedad social apoyan la validez discriminante. Las adecuadas propiedades psicométricas de la MAPS indican que puede ser aplicada con adolescentes españoles con fines clínicos y de investigación

Aids phobia is characterized by a persistent, intense and irrational fear of HIV. This fear is related to the infection stigma and the discrimination against HIV-positive people. The aim of this study was the adaptation and validation of the Multicomponent AIDS Phobia Scale (MAPS) with Spanish adolescents and to examine the structure of this fear among population from Spain and US. A sample of 832 secondary students from 14 to 18 years of age was recruited. The data provide evidence for two-factor structure of the scale, showing a composite reliability of .77. Convergent validity with the scores on HIV/aids knowledge and attitudes was adequate. Low correlations between the MAPS and the scores on health anxiety and social anxiety support the divergent validity. The MAPS has adequate psychometric properties and can be applied to Spanish adolescents for clinical and research purposes