Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry.

Induced oncoproteins degradation provides an attractive anti-cancer modality. Activation of anaphase-promoting complex (APC/CCDH1) prevents cell-cycle entry by targeting crucial mitotic proteins for degradation. Phosphorylation of its co-activator CDH1 modulates the E3 ligase activity, but little is known about its regulation after phosphorylation and how to effectively harness APC/CCDH1 activity to treat cancer. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)-catalyzed phosphorylation-dependent cis-trans prolyl isomerization drives tumor malignancy. However, the mechanisms controlling its protein turnover remain elusive. Through proteomic screens and structural characterizations, we identify a reciprocal antagonism of PIN1-APC/CCDH1 mediated by domain-oriented phosphorylation-dependent dual interactions as a fundamental mechanism governing mitotic protein stability and cell-cycle entry. Remarkably, combined PIN1 and cyclin-dependent protein kinases (CDKs) inhibition creates a positive feedback loop of PIN1 inhibition and APC/CCDH1 activation to irreversibly degrade PIN1 and other crucial mitotic proteins, which force permanent cell-cycle exit and trigger anti-tumor immunity, translating into synergistic efficacy against triple-negative breast cancer.

Impact of surgical preparatory rinses with isopropyl alcohol or water on perioperative body temperature in pediatric female dogs and cats.

OBJECTIVE: To describe the effects of presurgical preparation with an isopropyl alcohol or water rinse on the perioperative rectal temperature (RT) of puppies and kittens. STUDY DESIGN: Randomized clinical trial. ANIMALS: A total of 48 intact female mixed breed puppies and 43 intact female Domestic Short Hair kittens aged 8-18 weeks. METHODS: All animals were premedicated with intramuscular buprenorphine (0.02 mg kg-1) and acepromazine (0.05 mg kg-1). Anesthesia was induced with intravenous propofol (4 mg kg-1 to effect) for puppies or ketamine (5 mg kg-1) and midazolam (0.25 mg kg-1) for kittens. RT was measured every minute for the first 15 minutes at the beginning of hair/fur removal, then every 5 minutes for 45 minutes (dogs) and 35 minutes (cats). All animals were prepared for surgery using a 1.6% chlorhexidine solution, then rinsed with either isopropyl alcohol (group CA) or water (group CW). RESULTS: Mean RT difference between the groups was not significant at any time point. The mean RT at 45 minutes for dogs was 35.9 °C and 36.0 °C in groups CA and CW, respectively (p = 0.74). The mean RT at 35 minutes for cats was 35.1 °C in both groups (p = 0.84). CONCLUSIONS AND CLINICAL RELEVANCE: The use of either water or alcohol as a rinsing agent results in the same degree of perioperative temperature change. Other factors that contribute to perioperative hypothermia should be considered when choosing between these rinsing agents in surgical preparation of pediatric and small animals.

[Return to work after breast cancer: experience of an oncological referral centre in Medellín, Colombia]. / Reincorporación laboral de mujeres con cáncer de mama: experiencia de un centro oncológico en la ciudad de Medellín.

INTRODUCTION: Advances in the diagnosis and treatment of breast cancer have improved the prognosis for these patients. Consequently, a greater number of survivors are facing the process of returning to work. The objective of the present study was to analyze the frequency, median time and factors related to the return to work of patients with breast cancer, after diagnosis and completion of treatment at a cancer referral center in the city of Medellín, Colombia METHODS: a retrospective cohort study was carried out with registries of patients with breast cancer (n = 141) from a reference cancer center. Sociodemographic, occupational, treatment variables and prevalence of return to work were measured. RESULTS: The average age at diagnosis was 45.8 ± 9 years, Most of the women were premenopausal,and 45% performed manual labour. Advanced disease stage, manual labour, the presence of lymphedema and a greater number of episodes and days of disability werenegatively related to return to work. A total of 93% of patients returned to work. CONCLUSIONS: This study shows that return to work differs according to disease stage, treatment-related factors and type of work.

INTRODUCCIÓN: los avances en el diagnóstico y tratamiento del cáncer de mama han mejorado el pronóstico para estas pacientes, por lo tanto, se espera que un mayor número de supervivientes se enfrenten con el proceso de retornar al trabajo. El objetivo del presente estudio es analizar la frecuencia, la mediana del tiempo, así como los factores relacionados con el retorno al trabajo de pacientes con cáncer de mama, posterior al diagnóstico en un centro de referencia oncológico de la ciudad de Medellín, Colombia. MÉTODOS: estudio de cohorte retrospectiva realizado con los registros de pacientes con cáncer de mama (n=141) atendidas un centro oncológico de referencia. Se midieron variables sociodemográficas, laborales, relacionadas con el tratamiento y de retorno al trabajo. RESULTADOS: la edad promedio al diagnóstico fue de 45.8 ±9 años. La mayoría de las mujeres estaban en la premenopausia, el 45% realizaban trabajo manual. Los indicadores de mayor severidad de la enfermedad, así como el trabajo manual, la presencia de linfedema y un mayor número y días de incapacidad se relacionaron negativamente con el retorno al trabajo de estas pacientes. El 93% de las pacientes retornaron al trabajo. CONCLUSIONES: el retorno al trabajo después de un cáncer de mama difiere según la severidad de la enfermedad, factores relacionados con el tratamiento y tipo de trabajo.

Evaluation of cytology and histopathology for the diagnosis of feline orbital neoplasia: 81 cases (2004-2019) and review of the literature.

OBJECTIVE: To provide an updated overview of feline orbital neoplasia, to compare diagnostic utility of cytology and histopathology, and to evaluate minimally invasive sampling modalities. PROCEDURES: A medical records search was performed to identify cats with orbital neoplasia. Data were collected regarding signalment, diagnosis, vision status, imaging modalities, and sample collection methods. A reference population with orbital neoplasia was also identified via literature search for comparison with regard to final diagnosis. RESULTS: Eighty-one cats met selection criteria and 140 cases were identified in the literature. In the study and reference populations, respectively, diagnoses were grouped as follows: round cell tumors 47% and 24%, epithelial tumors 38% and 40%, mesenchymal tumors 14% and 34%, and neurologic origin tumors 1% and 2%. The most common diagnoses in both groups were lymphoma and squamous cell carcinoma (SCC). Feline restrictive orbital myofibroblastic sarcoma (FROMS) was common in the reference population but not diagnosed in the study population. Cytology results were available for 41 cats; histopathology results were available for 65 cats. Both cytology and histopathology results were available for 25 cats, in 44% of which cytologic results were overturned. No significant complications were associated with any sampling method. Lack of cats with multiple samples available for histopathology limited comparison between tissue sampling methods. CONCLUSIONS: Orbital neoplasia is common in cats, with round cell and epithelial tumors diagnosed most commonly in the study population. Histopathology is superior to cytology in providing a definitive diagnosis. Minimally invasive tissue biopsy techniques appear to be safe and effective.

IgG4-related disease: Is rituximab the best therapeutic strategy for cases refractory to conventional therapy? Results of a systematic review. / Enfermedad relacionada con IgG4: ¿es el rituximab la mejor estrategia terapéutica en los casos refractarios a terapia convencional? Resultados de una revisión sistemática.

INTRODUCTION: IgG4 related disease is a fibroinflammatory condition characterised by lymphoplasmocytic infiltration with predominance of IgG4+ plasma cells, fibrosis, and in most cases elevated IgG4 serum levels. It can affect any organ and result in varying clinical manifestations. Steroids are the cornerstone of treatment, however there is a high percentage of relapse. Recent studies have demonstrated favourable effects with rituximab. OBJECTIVE: To evaluate effectiveness related to the response to treatment with rituximab in patients with IgG4 related disease refractory to steroids and other immunosuppressant therapies. MATERIALS AND METHODS: We undertook a systematic search of the specialist databases EMBASE, LILACS, PUBMED and OVID-Cochrane for publications up until December 2017. RESULTS: After the quality analysis, we selected 27 articles (264 patients in total) for the final review, of which 23 were case reports and case series (105 patients), 3 were observational follow-up cohort studies (129 patients), and there was one clinical trial (30 patients). IgG4 related disease presents predominantly in male patients aged between 50 and 70 years on average. Multiple organs are compromised with an average of 3.5 compromised organs. Orbital, glandular and lymph-node compromise is most frequent. Patients in the different studies we included had received various treatments prior to starting rituximab, including glucocorticoids and disease-modifying anti-rheumatic drugs. There was 90.7% response in the cases where rituximab was used as second line therapy; rituximab was used as first line treatment for 10% of the patients with a 100% response rate. CONCLUSION: The use of rituximab for patients refractory to first-line treatments was associated with a high response percentage and less dependence on glucocorticoids.

Characterization of workers covered by a risk insurance company inColombia who suffered amputation / Caracterización de trabajadores amputados atendidos en una aseguradora de riesgos laborales en Colombia

| Background: Scarcity of information on the sociodemographic, occupational and clinical characteristics of workers who suffer upper limb amputation hinders planning and implementing actions to improve their living and working conditions. Objective: To investigate the sociodemographic, occupational and clinical characteristics of workers covered by a risk insurance company in Colombia who suffered upper limb amputations and investigate their association with risk categories. Methods: Exploratory, descriptive, retrospective and analytical study of data relative to workers covered by a risk insurance company in Colombia who suffered upper limb amputation in the period from 1982 and 2017. Following approval by School of Medicine, CES University, and a risk insurance company, we developed a checklist to collect data on the variables of interest. We performed descriptive and bivariate analysis with 95% of confidence and error of 5%. Results: The largest proportion of workers who suffered amputation were men aged 36 to 55 years old and residing in the Andean region of Colombia. Amputations mainly followed incidents during the performance of tasks, particularly in jobs in the secondary economic sector and classified as with type 3 risk. Conclusion: We were able to identify some characteristics associated with accidents, including age, risk class, economic sector, care received and disability duration. The results point to the need for appropriate interventions for the benefit of workers and risk insurance companies

| Introducción: La escasa información sobre las características sociodemográficas, laborales y clínicas de trabajadores que sufren amputaciones de miembro superior dificultan planear y adelantar acciones que aporten al mejoramiento de sus condiciones de vida y de salud. Objetivos: Determinar las características sociodemográficas, laborales y clínicas de trabajadores con amputaciones en miembros superiores atendidos en una aseguradora de riesgos laborales colombiana, para establecer una asociación con el tipo de riesgo. Métodos: Estudio exploratorio, descriptivo y retrospectivo con intención analítica. Se tomaron registros de la base de datos de pacientes con amputaciones de miembro superior atendidos en una aseguradora colombiana entre los años 1982 y 2017. Se aplicó una lista de chequeo, previa aprobación del proyecto por parte de la Facultad de Medicina de la Universidad CES y una aseguradora de riesgos laborales colombiana, para identificar las variables en estudio. Se realizaron análisis descriptivos y bivariados utilizando pruebas estadísticas con una confianza del 95% y un error del 5%. Resultados: Se observó que una mayor proporción de los trabajadores amputados fueron hombres entre 36 y 55 años de edad, residentes y trabajadores en la región andina. Las amputaciones fueron derivadas fundamentalmente de accidentes propios de su labor, particularmente para aquellos del sector secundario, clasificados como riesgo tipo 3. Conclusión: Se observaron algunas características asociadas a la accidentalidad laboral como edad, clasificación de riesgo, sector económico, tipo de atención hospitalaria requerida y días de incapacidad, evidenciando la importancia de intervenir adecuadamente para el beneficio de los pacientes y la aseguradora de riesgos laborales.

What happens to quality of life after the intensive care unit? Cross-sectional observational study / ¿Qué pasa con la calidad de vida después de la Unidad de Cuidados Intensivos? Estudio observacional de corte transversal

Abstract Introduction: Quality of life (QOL) of patients discharged from the intensive care unit (ICU) is affected by the procedures performed, and the sequelae and comorbidities associated with their etiology at the time of admission. Objective: To determine health-related QOL after discharge from an ICU between 2014 and 2016. Methods: Cross-sectional observational study that included patients over 50 years of age with a length of stay of more than 48 hours in an ICU. Demographic data were obtained from the clinical records, and an EQ-5D-3L survey was conducted by telephone. Data were analyzed using the SPSS version 21 software package. Results: Total mortality was 33.6%, and of these cases, 61.7% occurred within the first 6 months after discharge. Average total EQ-5D-3L results, where 0 is the worst result and 1 is the best in terms of QOL, was 0.65 and the most affected dimension was pain/ discomfort. On the analog quality-of-life scale, the total average was 69.05%. Conclusion: QOL is impacted negatively following discharge from the ICU, especially in patients over 80 years of age. The most affected dimensions are pain/discomfort and anxiety/depression. Moreover, more than 1/3 of patients die within the first 6 months after discharge.

Resumen Introducción: Para los pacientes que egresan de una unidad de cuidados intensivos, los procedimientos realizados, las secuelas y las comorbilidades asociadas a su etiología de ingreso afectan su calidad de vida. Objetivo: Determinar la calidad de vida relacionada a la salud posterior al egreso de una unidad de cuidados intensivos entre 2014 - 2016. Métodos: El siguiente es un estudio observacional de corte transversal, donde se incluyeron pacientes mayores de 50 años con una estancia en una unidad de cuidados intensivos superior a 48 horas. Se obtuvieron datos demográficos de las historias clínicas y se realizó el cuestionario EQ-5D-3L vía telefónica. El análisis de la información se llevó a cabo utilizando SPSS ® versión 21. Resultados: Seobtuvounamortalidadtotaldel33.6%,delacualel 61.7% sucedió en los primeros 6 meses posterior al alta médica. El promedio en el total del resultado del EQ-5D-3L fue de 0.65 y la dimensiónmásafectadafuedolor/malestar. Siendo0elpeorresultado de la escala y 1 el mejor en cuanto a calidad de vida. En cuanto a la escala análoga de calidad de vida, el promedio total fue de 69.05%. Conclusión: La calidad de vida tiene un impacto negativo después del egreso de la unidad de cuidados intensivos, especialmente en aquellos pacientes mayores de 80 años. Las dimensiones más afectadas son dolor/malestar y ansiedad/ depresión. Además, la mortalidad es superior a un tercio en los primeros seis meses después del alta.

Characterization of workers covered by a risk insurance company in Colombia who suffered amputation.

BACKGROUND: Scarcity of information on the sociodemographic, occupational and clinical characteristics of workers who suffer upper limb amputation hinders planning and implementing actions to improve their living and working conditions. OBJECTIVE: To investigate the sociodemographic, occupational and clinical characteristics of workers covered by a risk insurance company in Colombia who suffered upper limb amputations and investigate their association with risk categories. METHODS: Exploratory, descriptive, retrospective and analytical study of data relative to workers covered by a risk insurance company in Colombia who suffered upper limb amputation in the period from 1982 and 2017. Following approval by School of Medicine, CES University, and a risk insurance company, we developed a checklist to collect data on the variables of interest. We performed descriptive and bivariate analysis with 95% of confidence and error of 5%. RESULTS: The largest proportion of workers who suffered amputation were men aged 36 to 55 years old and residing in the Andean region of Colombia. Amputations mainly followed incidents during the performance of tasks, particularly in jobs in the secondary economic sector and classified as with type 3 risk. CONCLUSION: We were able to identify some characteristics associated with accidents, including age, risk class, economic sector, care received and disability duration. The results point to the need for appropriate interventions for the benefit of workers and risk insurance companies.

INTRODUCCIÓN: La escasa información sobre las características sociodemográficas, laborales y clínicas de trabajadores que sufren amputaciones de miembro superior dificultan planear y adelantar acciones que aporten al mejoramiento de sus condiciones de vida y de salud. OBJETIVOS: Determinar las características sociodemográficas, laborales y clínicas de trabajadores con amputaciones en miembros superiores atendidos en una aseguradora de riesgos laborales colombiana, para establecer una asociación con el tipo de riesgo. MÉTODOS: Estudio exploratorio, descriptivo y retrospectivo con intención analítica. Se tomaron registros de la base de datos de pacientes con amputaciones de miembro superior atendidos en una aseguradora colombiana entre los años 1982 y 2017. Se aplicó una lista de chequeo, previa aprobación del proyecto por parte de la Facultad de Medicina de la Universidad CES y una aseguradora de riesgos laborales colombiana, para identificar las variables en estudio. Se realizaron análisis descriptivos y bivariados utilizando pruebas estadísticas con una confianza del 95% y un error del 5%. RESULTADOS: Se observó que una mayor proporción de los trabajadores amputados fueron hombres entre 36 y 55 años de edad, residentes y trabajadores en la región andina. Las amputaciones fueron derivadas fundamentalmente de accidentes propios de su labor, particularmente para aquellos del sector secundario, clasificados como riesgo tipo 3. CONCLUSIÓN: Se observaron algunas características asociadas a la accidentalidad laboral como edad, clasificación de riesgo, sector económico, tipo de atención hospitalaria requerida y días de incapacidad, evidenciando la importancia de intervenir adecuadamente para el beneficio de los pacientes y la aseguradora de riesgos laborales.

Radiación ionizante: revisión de tema y recomendaciones para la práctica / Ionising radiation: A review of the topic and recommendations for using it

Resumen La seguridad en radiación es un tema de actualidad. A diario se evidencian las consecuencias deletéreas de esta herramienta diagnóstica y terapéutica. En su mayoría, las patologías asociadas secundarias a la exposición por radiación podrían prevenirse con una adecuada intervención preventiva y protectora. Se presenta un artículo de revisión con el fin de explicar de forma detallada los aspectos más relevantes acerca de la formación de los rayos X, su definición y clasificación dosimétrica, los efectos biológicos de la radiación, los límites recomendados y las medidas de protección para la exposición de radiación.

Abstract Radiation safety is a current topic. The harmful effects of this diagnostic and therapeutic tool are observed daily. The majority of associated secondary to radiation exposure could be prevented with suitable safety and protective measures. A review article is presented with the aim of explaining the most relevant aspects of radiation in detail, including the formation of x-rays, their dosimetry definition and classification, the biological effects of radiation, the recommended limits, as well as the protection measures for the exposure to radiation.