Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

Background

Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors.

Design and Methods

We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation.

Results

We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice.

Conclusions

These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment.Key words: human induced pluripotent stem cells, terminal maturation, erythropoietic differentiation     

Preliminary reliability and validity testing of a Self-Efficacy Questionnaire for Chinese Family Caregivers

Objectives: To develop and test preliminary reliability and validity of a Self-Efficacy Questionnaire for Chinese Family Caregivers (SEQCFC).

Methods: A cross-sectional survey of 196 family caregivers (CGs) of people with dementia (CGs) was conducted to determine the factor structure of a SEQCFC of people with dementia. Following factor analyses, preliminary testing was performed, including internal consistency, 4-week test-retest reliability, and construct and convergent validity.

Results: Factor analyses with direct oblimin rotation were performed. Eight items were removed and five subscales (self-efficacy for gathering information about treatment, symptoms and health care; obtaining support; responding to behaviour disturbances; managing household, personal and medical care; and managing distress associated with caregiving) were identified. The Cronbach's alpha coefficients for the whole scale and for each subscale were all over 0.80. The 4-week test-retest reliabilities for the whole scale and for each subscale ranged from 0.64 to 0.85. The convergent validity was acceptable.

Conclusions: Evidence for the preliminary testing of the SEQCFC was encouraging. A future follow-up study using confirmatory factor analysis with a new sample from different recruitment centres in Shanghai will be conducted. Future psychometric property testings of the questionnaire will be required for CGs from other regions of mainland China.     

Development of an Optimally Reliable Short Form for Judgment of Line Orientation

Standard and short forms of Judgment of Line Orientation-Form V (JLO; Benton, Sivan, Hamsher, Varney, & Spreen, 1994) were examined for internal consistency (coefficient alpha) in a diagnostically mixed neuropsychiatric sample (N = 230). Equivalence of internally consistent short forms was assessed by correlating them with the full form of the test. Internal consistency for the full 30-item form of JLO (alpha = .84) approximated the optimal level of .80 (Nunnally, 1978). Two 20-item short forms of JLO (items V1-V20 and items V11-V30) also reached comparable alpha levels (alpha = .75 and .80, respectively). These two JLO short forms correlated .90 and .97, respectively, with the full 30-item form. We recommend the JLO short form based on items V11-V30 for clinical use in situations in which employment of the full form may not be advisable and offer a short-to-long-form conversion table for clinical use.     

Comparing how significantly the pharmacological treatment of genitourinary cancer in a non-curative setting affects endpoints of survival or response

Prevalence of advanced genitourinary cancer is high considering approximately 70,000 patients die annually of prostate, bladder and kidney cancer in the United States. Treatment is non-curative but along with the aim of relieving symptoms and improving quality of life, patients and doctors are driven by the goal of prolonging life. In modern urological practice, with the ever increasing number of novel therapies, clinical benefit to patients has to be measured by evaluating the trial endpoints of response and survival against adverse events. This is especially true as the population with advanced cancer is increasingly older and co-morbid. Currently, we are in a time of exponential drug development, innumerable registered trials and a vast amount of expenditure on pharmacological cancer treatment. In this era of financial uncertainty, it is even more important for clinicians to objectively assess the benefit of these expensive, moderately effective treatments that still have associated adverse sequelae. We aim to highlight the pivotal data available and put into context the survival benefit we can currently achieve with the pharmacological treatment of advanced genitourinary cancer, allowing us to critically judge whether a potentially toxic systemic treatment is worthwhile or whether it is better to defer to best supportive care. The figures presented are from the key publications that form the basis of international guideline recommendations and are the standard that newly developed treatments must emulate.     

A Cross-Cultural Study of Disordered Eating Attitudes Among Filipino and Caucasian Americans

The present study examines the symptom levels of eating disorders among Filipino and Caucasian college students residing in Hawaii. The study also examines what variables are associated with disordered eating. A self-report questionnaire that included measures of anger discomfort, self-dissatisfaction, body dissatisfaction, and symptoms of eating disorders was administered to Filipino and Caucasian college students. As predicted, females reported higher eating disorder symptom scores than males. However, Filipino males reported higher levels of disordered eating, dieting, and body dissatisfaction than Caucasian males. No association was found between disordered eating and anger discomfort among Filipinos. The results support previous findings of females reporting higher disordered eating attitudes than males, however, Filipino males reported higher disordered attitudes than Caucasian males. Anger discomfort was not associated with disordered eating among Filipinos, supporting past studies that suggest anger management may not be an appropriate treatment for disordered eating among some Asian groups.