Evaluation of a Multi-Gene Methylation Blood-Test for the Detection of Colorectal Cancer.

Circulating tumour DNA biomarkers are an expanding field in oncology research that offer great potential but are currently often limited in value by overall cost. The aim of this study was to evaluate the efficacy of a novel multi-gene methylation blood test for the identification of colorectal cancer and throughout the spectrum of colorectal disease. Participants were recruited either prior to resection for known CRC or prior to screening colonoscopy after a positive faecal immunochemical test. Blood was collected from participants prior to their procedure being performed. The plasma was separated, and multiplex MethylLight droplet digital PCR was used to analyse for the presence of four methylated genes: SDC2, NPY, IKZF1 and SEPT9. A total of 537 participants underwent analysis. The SDC2/NPY genes showed a sensitivity of 33-54% and a specificity of 72-96%, whilst the IKZF1/SEPT9 genes showed a sensitivity of 19-42% and a specificity of 88-96%. Combining the two tests did not significantly increase the test accuracy. The sensitivity for advanced adenoma was 2-15%. There was a significant difference in the frequency of detectable methylation between the participants with CRC and those without CRC. However, neither the sensitivity nor the specificity was superior to current diagnostic screening tests.

Investigating skewness to understand gene expression heterogeneity in large patient cohorts.

BACKGROUND: Skewness is an under-utilized statistical measure that captures the degree of asymmetry in the distribution of any dataset. This study applied a new metric based on skewness to identify regulators or genes that have outlier expression in large patient cohorts. RESULTS: We investigated whether specific patterns of skewed expression were related to the enrichment of biological pathways or genomic properties like DNA methylation status. Our study used publicly available datasets that were generated using both RNA-sequencing and microarray technology platforms. For comparison, the datasets selected for this study also included different samples derived from control donors and cancer patients. When comparing the shift in expression skewness between cancer and control datasets, we observed an enrichment of pathways related to the immune function that reflects an increase towards positive skewness in the cancer relative to control datasets. A significant correlation was also detected between expression skewness and the top 500 genes corresponding to the most significant differential DNA methylation occurring in the promotor regions for four Cancer Genome Atlas cancer cohorts. CONCLUSIONS: Our results indicate that expression skewness can reveal new insights into transcription based on outlier and asymmetrical behaviour in large patient cohorts.

Relación entre características sociodemográficas y clínicas de pacientes con Alzheimer y sobrecarga del cuidador principal / Relationship between sociodemography and clinical characteristics of patients with Alzheimer disease and overload of principal caregiver

RESUMEN Introducción: la enfermedad de Alzheimer constituye un proceso degenerativo y progresivo del cerebro. Cursa por estadios: leve, moderado y severo; en los cuales el paciente va perdiendo sus capacidades mentales, por lo que se hace dependiente y necesita del cuidado de otros. El cuidado a estos pacientes tiene consecuencias para el cuidador y la familia. Objetivo: relacionar la sobrecarga percibida por el cuidador principal con las características sociodemográficas y clínicas de pacientes con enfermedad de Alzheimer. Métodos: estudio descriptivo correlacional en el Policlínico Carlos Manuel Portuondo en Marianao. El universo de estudio estuvo constituido por 35 pacientes con enfermedad de Alzheimer en las fases leve y moderada y sus cuidadores principales. Para recolectar la información se utilizó un cuestionario sociodemográfico y la Escala de Zarit. Se conformó una base de datos con el SPSS 15.0 para Windows. Se utilizó el coeficiente de correlación de Pearson para la relación entre variables, los resultados se presentaron en tabla de contingencia. Resultados: en los pacientes se obtuvo una edad media de 77,06 años, el 80,00 por ciento fueron mujeres, el 42,85 por ciento, casados e igual porcentaje con preuniversitario terminado, el 74,28 por ciento en la fase leve de la enfermedad. El 74,3 por ciento de los cuidadores experimentaron niveles de sobrecarga debido a la labor del cuidado. Existe relación significativa entre la sobrecarga percibida por el cuidador y el estadio de la enfermedad (r=0,346). Conclusiones: se constató una relación significativa entre los estadios de la enfermedad de Alzheimer y la sobrecarga percibida por el cuidador(AU)

ABSTRACT Introduction: The Alzheimer´s disease is a degenerative and progressive change in the brain. It course consists of different stages: mild, moderate and severe, where the patients loss mental capacities slowly and depend on and needs care from other person. The incessant care to this patient generate bad consequences to the caregiver and family as well. Objective: To correlate the perceived overload of the principal caregiver with the socioeconomic and clinical characteristics of Alzheimer disease. Methods: A descriptive correlational study was conducted at the Polyclinic Carlos Manuel Portuondo in Marianao. The study group consisted of 35 patients with Alzheimer's disease in mild to moderate stages and their primary caregivers. To gather information was used a sociodemographic questionnaire and the Scale of Zarit. A database using SPSS 15.0 for Windows was formed. The Pearson correlation coefficient for the relationship between variables was used, the results were presented in contingency table. Results: In patients with a mean age of 77.06 years was obtained, the women were 80.00 percent, 42.85 percent married and the same percentage finished high school, the 74.28 percent in the mild stage of the disease. 74.3 percent of caregivers experienced levels of overload due to the work of care. There is significant relationship between perceived caregiver overload and stage of disease (r = 0.346). Conclusions: A significant relationship between the stages of Alzheimer's disease and perceived by the caregiver overload was found(AU)

Distinct patterns of infiltrating CD8+ T cells in HPV+ and CD68 macrophages in HPV- oropharyngeal squamous cell carcinomas are associated with better clinical outcome but PD-L1 expression is not prognostic.

Immunotherapies are beginning to revolutionise treatment paradigms in oncology with monoclonal antibodies (mAb) targeting T-cell co-inhibitory (e.g. PD-1/PD-L1) and co-stimulatory pathways (e.g. CTLA-4/CD28) demonstrating clinical utility. Some clinical studies demonstrate that responsiveness to PD-1/PD-L1 mAb therapy is greater in patients with expression of PD-L1 in the tumour microenvironment. However, robust responses have also been observed in patients with low or absent expression of PD-L1. Using multiplex immuno-fluorescent labelling we sought to determine how infiltration of tumours by CD8+ T-cells, their expression of PD-1, and the expression of PD-L1 on both tumours and CD68 cells (macrophages) correlated with HPV status and outcome in a cohort of 124 oropharyngeal squamous cell carcinomas (OPSCC).

Natural product HTP screening for antibacterial (E.coli 0157:H7) and anti-inflammatory agents in (LPS from E. coli O111:B4) activated macrophages and microglial cells; focus on sepsis.

BACKGROUND: Acute systemic inflammatory response syndrome arising from infection can lead to multiple organ failure and death, with greater susceptibility occurring in immunocompromised individuals. Moreover, sub-acute chronic inflammation is a contributor to the pathology of diverse degenerative diseases (Parkinson's disease, Alzheimer's disease and arthritis). Given the known limitations in Western medicine to treat a broad range of inflammatory related illness as well as the emergence of antibiotic resistance, there is a renewed interest in complementary and alternative medicines (CAMs) to achieve these means. METHODS: A high throughput (HTP) screening of >1400 commonly sold natural products (bulk herbs, cooking spices, teas, leaves, supplement components, nutraceutical food components, fruit and vegetables, rinds, seeds, polyphenolics etc.) was conducted to elucidate anti-inflammatory substances in lipopolysaccharide (LPS) (E. coli serotype O111:B4) monocytes: RAW 264.7 macrophages [peripheral], BV-2 microglia [brain]) relative to hydrocortisone, dexamethasone and L-N6-(1Iminoethyl)lysine (L-NIL). HTP evaluation was also carried out for lethal kill curves against E.coli 0157:H7 1x106 CFU/mL relative to penicillin. Validation studies were performed to assess cytokine profiling using antibody arrays. Findings were corroborated by independent ELISAs and NO2-/iNOS expression quantified using the Griess Reagent and immunocytochemistry, respectively. For robust screening, we developed an in-vitro efficacy paradigm to ensure anti-inflammatory parameters were observed independent of cytotoxicity. This caution was taken given that many plants exert tumoricidal and anti-inflammatory effects at close range through similar signaling pathways, which could lead to false positives. RESULTS: The data show that activated BV-2 microglia cells (+ LPS 1µg/ml) release >10-fold greater IL-6, MIP1/2, RANTES and nitric oxide (NO2-), where RAW 264.7 macrophages (+ LPS 1µg/ml) produced > 10-fold rise in sTNFR2, MCP-1, IL-6, GCSF, RANTES and NO2-. Data validation studies establish hydrocortisone and dexamethasone as suppressing multiple pro-inflammatory processes, where L-NIL suppressed NO2-, but had no effect on iNOS expression or IL-6. The screening results demonstrate relative few valid hits with anti-inflammatory effects at < 250µg/ml for the following: Bay Leaf (Laurus nobilis), Elecampagne Root (Inula helenium), Tansy (Tanacetum vulgare),Yerba (Eriodictyon californicum) and Centipeda (Centipeda minima), Ashwagandha (Withania somnifera), Feverfew (Tanacetum parthenium), Rosemary (Rosmarinus officinalis), Turmeric Root (Curcuma Longa), Osha Root (Ligusticum porteri), Green Tea (Camellia sinensis) and constituents: cardamonin, apigenin, quercetin, biochanin A, eupatorin, (-)-epigallocatechin gallate (EGCG) and butein. Natural products lethal against [E. coli 0157:H7] where the LC50 < 100 µg/ml included bioactive silver hydrosol-Argentyn 23, green tea (its constituents EGCG > Polyphenon 60 > (-)-Gallocatechin > Epicatechin > (+)-Catechin), Grapeseed Extract (Vitis vinifera), Chinese Gallnut (its constituents gallic acid > caffeic acid) and gallic acid containing plants such as Babul Chall Bark (Acacia Arabica), Arjun (Terminalia Arjuna) and Bayberry Root Bark (Morella Cerifera). CONCLUSIONS: These findings emphasize and validate the previous work of others and identify the most effective CAM anti-inflammatory, antibacterial compounds using these models. Future work will be required to evaluate potential combination strategies for long-term use to prevent chronic inflammation and possibly lower the risk of sepsis in immunocompromised at risk populations.

Características sociodemográficas de pacientes con enfermedad de Alzheimer y sus cuidadores principales / Characteristic sociodemográficas of patient with illness of Alzheimer and their main caretakers

Introducción: lograr la plena integración del adolescente con discapacidad constituye una meta central de los programas de rehabilitación; contra esto conspira en gran medida la presencia de conceptos errados en la población, que considera al discapacitado en desventaja, especialmente en lo referido a la vida sexual. Objetivo: identificar el nivel de conocimientos de los estudiantes de la carrera de licenciatura en enfermería en la ciudad de Camagüey sobre el tema de la sexualidad entre los adolescentes con discapacidad. Métodos: estudio cualitativo mediante encuestas y entrevistas aplicadas, que fueron objeto de análisis de contenido. La muestra quedó integrada por 80 estudiantes de diversos años de la carrera de licenciatura en enfermería. Se aplicó una entrevista a 45 estudiantes de primer y segundo año de la carrera de licenciatura en enfermería, y una encuesta de preguntas cerradas para obtener respuestas dicotómicas a 35 estudiantes del tercer y cuarto año. Resultados: el 62 por ciento de los entrevistados argumentaron diversas razones que limitaban las posibilidades del desarrollo sexual en los discapacitados, y en la encuesta aplicada el 60 por ciento de las respuestas resultaron incorrectas. Conclusiones: resulta necesario el desarrollo de programas de educación sexual ajustados a las necesidades especiales de la población discapacitada, y divulgar información en la población, en estudiantes y profesionales de la salud sobre este tema(AU)

Introduction: alzheimer disease is one of the most common dementia. It is destructive that affects the life quality of patients and their principal care givers. Objective: to characterize patients with mild and moderate Alzheimer disease and their principal care givers. Methods: it was carried out a descriptive study that included 35 patients with mild and moderate Alzheimer disease and their principal care givers, who resides in Carlos Manuel Portuondo health area in Marianao. It was carried out a socio demographic test to characterize patients and their principal care givers. To proses and statistical analysis off the results it was created a data base with statistical program SPSS 15.0 for Windows. Results: it had a predominance of female patients in mild phase. The principal care givers was the daughter, who was married, they had not job and suffered some chronic disease non transmit. Conclusions: the socio demographic characteristics of patients with Alzheimer disease and their principal care givers show the repercussion of disease in psychologist, social and economic order and principal care giver´s health(AU)

Systemic lupus erythematosus, meningioma and carcinoma of the cervix--a case report. 1956.

The history of a patient with systemic lupus erythematosus, meningioma and carcinoma of the cervix is presented. Although the meningioma originally masqueraded as a cerebral manifestation of lupus, lack of response to cortisone and progression of symptoms eventually indicated the diagnosis of brain tumor. Carcinoma-in-situ of the cervix was discovered incidentally as a result of routine cervical exfoliative cytological studies. The case history emphasizes the importance of individual evaluation of every patient.