Characterization of iPS87, a prostate cancer stem cell-like cell line.

Prostate cancer affects hundreds of thousands of men and families throughout the world. Although chemotherapy, radiation, surgery, and androgen deprivation therapy are applied, these therapies do not cure metastatic prostate cancer. Patients treated by androgen deprivation often develop castration resistant prostate cancer which is incurable. Novel approaches of treatment are clearly necessary. We have previously shown that prostate cancer originates as a stem cell disease. A prostate cancer patient sample, #87, obtained from prostatectomy surgery, was collected and frozen as single cell suspension. Cancer stem cell cultures were grown, single cell-cloned, and shown to be tumorigenic in SCID mice. However, outside its natural niche, the cultured prostate cancer stem cells lost their tumor-inducing capability and stem cell marker expression after approximately 8 transfers at a 1:3 split ratio. Tumor-inducing activity could be restored by inducing the cells to pluripotency using the method of Yamanaka. Cultures of human prostate-derived normal epithelial cells acquired from commercial sources were similarly induced to pluripotency and these did not acquire a tumor phenotype in vivo. To characterize the iPS87 cell line, cells were stained with antibodies to various markers of stem cells including: ALDH7A1, LGR5, Oct4, Nanog, Sox2, Androgen Receptor, and Retinoid X Receptor. These markers were found to be expressed by iPS87 cells, and the high tumorigenicity in SCID mice of iPS87 was confirmed by histopathology. This research thus characterizes the iPS87 cell line as a cancer-inducing, stem cell-like cell line, which can be used in the development of novel treatments for prostate cancer.

Comparison of essential medicines lists in 137 countries.

OBJECTIVE: To compare the medicines included in national essential medicines lists with the World Health Organization's (WHO's) Model list of essential medicines, and assess the extent to which countries' characteristics, such as WHO region, size and health care expenditure, account for the differences. METHODS: We searched the WHO's Essential Medicines and Health Products Information Portal for national essential medicines lists. We compared each national list of essential medicines with both the 2017 WHO model list and other national lists. We used linear regression to determine whether differences were dependent on WHO Region, population size, life expectancy, infant mortality, gross domestic product and health-care expenditure. FINDINGS: We identified 137 national lists of essential medicines that collectively included 2068 unique medicines. Each national list contained between 44 and 983 medicines (median 310: interquartile range, IQR: 269 to 422). The number of differences between each country's essential medicines list and WHO's model list ranged from 93 to 815 (median: 296; IQR: 265 to 381). Linear regression showed that only WHO region and health-care expenditure were significantly associated with the number of differences (adjusted R2 : 0.33; P < 0.05). Most medicines (1248; 60%) were listed by no more than 10% (14) of countries. CONCLUSION: The substantial differences between national lists of essential medicines are only partly explained by differences in country characteristics and thus may not be related to different priority needs. This information helps to identify opportunities to improve essential medicines lists.

Assessing wellness in the well-child check: What about social and emotional development?

OBJECTIVE: To determine whether Canadian children aged 4 to 6 received well-child checks; to explore the nature of these checkups in a large family practice; and to examine the merit of using parent questionnaires about child resilience as a means of introducing a discussion about social and emotional development into this checkup. DESIGN: Three-part mixed-methods study, using data derived from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), chart reviews of a family practice, and semistructured interviews with parents. SETTING: Primary care practices associated with CPCSSN, and a large primary care practice in Kingston, Ont. PARTICIPANTS: Patients who were born between 2008 and 2011, and a sample of parents whose children were between the ages of 6 and 9. METHODS: International Classification of Diseases, version 9, codes from CPCSSN records were used to identify the prevalence of well-child checks in the 4-to-6 age group. Then 110 randomly selected charts from a large family practice were audited for inclusion of behavioural and social assessments of those aged 4 to 6. Finally, randomly selected parents from the same practice were invited to pilot-test the PERIK (Positive development and resilience in kindergarten) resilience questionnaire, interviewed about its merit, and asked to recall whether the identified areas of child development had been included in previous well-child checkups. MAIN FINDINGS: Data from CPCSSN indicated that 11% of Canadian children aged 4 to 6 had had an explicit well-child check by their family physician. Among the reviewed charts from the one practice, social context was documented for 45% of them, but social and behavioural development was usually not recorded. The 42 parents interviewed found the PERIK questionnaire useful, but not perfect, for opening discussions about aspects of child development that they had not realized were central to the child's future health. CONCLUSION: This study offers an initial approach to exploring resilience in children and therefore addressing recognized and alterable predictors of adult well-being. Early social and emotional development predicts resilience that, in turn, foreshadows future health. The PERIK questionnaire facilitated discussions that could add tremendous value to the well-child checks of children aged 4 to 6.

Diabetes Canada 2018 clinical practice guidelines: Key messages for family physicians caring for patients living with type 2 diabetes.

OBJECTIVE: To summarize the 2018 Diabetes Canada clinical practice guidelines, focusing on high-priority recommendations for FPs managing people who live with type 2 diabetes. QUALITY OF EVIDENCE: A prioritization process was conducted to focus the efforts of Diabetes Canada's guideline dissemination and implementation efforts. The resulting identified key messages for FPs to consider when managing patients with type 2 diabetes are described. Evidence supporting the guideline recommendations ranges from levels I to IV and grades A to D. MAIN MESSAGE: Three key messages were identified from the 2018 guidelines as priorities for FPs: discussing opportunities to reduce the risk of diabetes complications, discussing opportunities to ensure safety and prevent hypoglycemia, and discussing progress on self-management goals and addressing barriers. A theme cutting across these key messages was the need to tailor discussions to the needs and preferences of each person. These important guideline recommendations are highlighted, along with information about relevant tools for implementing the recommendations in real-world practice. CONCLUSION: High-quality diabetes care involves a series of periodic conversations about self-management and about pharmacologic and nonpharmacologic treatments that fit with each patient's goals (ie, shared decision making). Incorporating these conversations into regular practice provides FPs with opportunities to maximize likely benefits of treatments and decrease the risk of harms, to support patients in initiating and sustaining desired lifestyle changes, and to help patients cope with the burdens of diabetes and comorbid conditions.

Lignes directrices de pratique clinique 2018 de Diabète Canada: Principaux messages à l'intention des médecins de famille qui traitent les patients atteints de diabète de type 2.

OBJECTIF: Résumer les lignes directrices de pratique clinique 2018 de Diabète Canada en s'attardant aux recommandations prioritaires pour les médecins de famille qui traitent des personnes vivant avec le diabète de type 2. QUALITÉ DES DONNÉES: Un processus de priorisation a été réalisé dans le but de canaliser les efforts de dissémination et de mise en oeuvre des lignes directrices de Diabète Canada. Il en a résulté une description des principaux messages à l'intention des médecins de famille qui soignent des patients de diabète de type 2. Les données étayant les recommandations des lignes directrices varient des niveaux I à IV, et des catégories A à D. MESSAGE PRINCIPAL: Trois principaux messages prioritaires pour les médecins de famille ont été relevés dans les lignes directrices 2018 : parler des occasions de réduire le risque de complications du diabète, parler des occasions d'assurer la sécurité et de prévenir l'hypoglycémie, et parler des progrès vers l'atteinte des objectifs d'autoprise en charge et de l'élimination des obstacles. Ces principaux messages ont fait ressortir un thème : celui d'adapter les conversations aux besoins et aux préférences de chacun. Ces importantes recommandations sont mises en lumière, de même que l'information sur les outils pertinents pour mettre en oeuvre les recommandations en pratique réelle. CONCLUSION: Les soins du diabète de grande qualité comprennent une série de conversations périodiques sur l'autoprise en charge, et sur les traitements pharmacologiques et non pharmacologiques adaptés aux objectifs de chaque patient (c.-à-d. prise de décision partagée). Lorsque les médecins de famille incorporent ces conversations dans la pratique régulière, ils ont la chance d'optimiser les bienfaits possibles du traitement et de réduire le risque d'effets nuisibles, d'encourager les patients à instaurer et à maintenir les modifications désirées du mode de vie, et de les aider à composer avec le fardeau du diabète et des comorbidités.

Visualization of early prostatic adenocarcinoma as a stem cell disease.

Prostate Cancer represents the second leading cause of cancer death among men in the United States, and the third leading cause of cancer death among men in Europe. We have previously shown that cells possessing Cancer Stem Cell (CSC) characteristics can be grown from human PrCa tissue harvested at the time of prostatectomy. However, the cellular origin of these CSCs was not previously known. In most cases, simple hematoxylin and eosin (H&E) stained sections are sufficient to make a definitive diagnosis of prostatic adenocarcinoma (PrCa) in needle biopsy samples. We utilized six different antibodies specific for stem cell antigens to examine paraffin sections of PrCa taken at the time of needle-biopsy diagnosis. These antisera were specific for CD44, CD133, ALDH7A1, LGR-5, Oct-4 and NANOG. We demonstrate specific staining of tumor cells with all six antisera specific for stem cell antigens. Some of these antibodies also react with cells of hyperplastic glands, but the patterns of reactivity differ from those of malignant glands. These findings demonstrate that at the time of diagnosis, PrCa consists of cells exhibiting properties of CSCs and consistent with the possibility that PrCa is a stem cell disease.

Early oxidative shifts in mouse skeletal muscle morphology with high-fat diet consumption do not lead to functional improvements.

Short-term consumption of a high-fat diet (HFD) can result in an oxidative shift in adult skeletal muscle. However, the impact of HFD on young, growing muscle is largely unknown. Thus, 4-week-old mice were randomly divided into sedentary HFD (60% kcal from fat), sedentary standard chow (control), or exercise-trained standard chow. Tibialis anterior (TA) and soleus muscles were examined for morphological and functional changes after 3 weeks. HFD consumption increased body and epididymal fat mass and induced whole body glucose intolerance versus control mice. Compared to controls, both HFD and exercise-trained TA muscles displayed a greater proportion of oxidative fibers and a trend for an increased succinate dehydrogenase (SDH) content. The soleus also displayed an oxidative shift with increased SDH content in HFD mice. Despite the aforementioned changes, palmitate oxidation rates were not different between groups. To determine if the adaptive changes with HFD manifest as a functional improvement, all groups performed pre- and postexperiment aerobic exercise tests. As expected, exercise-trained mice improved significantly compared to controls, however, no improvement was observed in HFD mice. Interestingly, capillary density was lower in HFD muscles; a finding which may contribute to the lack of functional differences seen with HFD despite the oxidative shift in skeletal muscle morphology. Taken together, our data demonstrate that young, growing muscle exhibits early oxidative shifts in response to a HFD, but these changes do not translate to functional benefits in palmitate oxidation, muscle fatigue resistance, or whole body exercise capacity.