Ethical Considerations in Conducting Research on Autism Spectrum Disorders in Low and Middle Income Countries

Autism spectrum disorder (ASD) is being identified in an ever-increasing number of countries, including many that are low or middle income (LMIC). Research conducted in these countries requires awareness of unique ethical issues. Drawing on the experience of two organizations that have been involved in conducting and collaborating in ASD research in India, we describe specific considerations in conducting epidemiological, genetic and treatment studies as well as general principles from the field of multinational clinical research as they apply to the conduct of ASD research. We argue that greater attention to ethical concerns will result in quality studies conducted in LMICs that are also of greatest relevance for families and children with ASD.     

International standards for tuberculosis care: relevance and implications for laboratory professionals

On World Tuberculosis (TB) Day 2006, the International Standards for Tuberculosis Care (ISTC) was officially released and widely endorsed by several agencies and organizations. The ISTC release was the culmination of a year long global effort to develop and set internationally acceptable, evidence-based standards for tuberculosis care. The ISTC describes a widely endorsed level of care that all practitioners, public and private, should seek to achieve in managing individuals who have or are suspected of having, TB and is intended to facilitate the effective engagement of all healthcare providers in delivering high quality care for patients of all ages, including those with smear-positive, smear-negative and extra-pulmonary TB, TB caused by drug-resistant Mycobacterium tuberculosis and TB/HIV coinfection. In this article, we present the ISTC, with a special focus on the diagnostic standards and describe their implications and relevance for laboratory professionals in India and worldwide. Laboratory professionals play a critical role in ensuring that all the standards are actually met by providing high quality laboratory services for smear microscopy, culture and drug susceptibility testing and other services such as testing for HIV infection. In fact, if the ISTC is widely followed, it can be expected that there will be a greater need and demand for quality assured laboratory services and this will have obvious implications for all laboratories in terms of work load, requirement for resources and trained personnel and organization of quality assurance systems.     

Is Long-Acting Reversible Contraceptive Use Increasing? Assessing Trends Among U.S. College Women, 2008–2013

Objective To assess LARC use trends among college women (18–24 years) and identify groups that have increased LARC use. Methods Data were extracted from the National College Health Assessment-II (NCHA-II) fall 2008–2013 surveys. Logistic regression statistics were used to assess LARC use. Results Although LARC use increased from 2008 to 2013 (aOR?=?2.62; 95% CI 2.23–3.07), less than half of the sample (44%) reported using contraception at last vaginal sex. Only 2.5% of college women in this study reported using a LARC method; of LARC users, 90% reported using an intrauterine device. Nearly all sociodemographic factors were significantly associated with increases in LARC use including: age, sexual orientation, and insurance status. Conclusions LARC use significantly increased among college women. However, less effective methods such as condoms and short-acting reversible contraceptives are used more frequently. Promoting LARC use for women who desire to effectively prevent pregnancy can reduce unintended pregnancy and improve health outcomes for women while in college. Future work should examine the importance of individual and lifestyle factors that influence college women’s decision to choose a LARC method and seek to eliminate barriers to college women choosing a contraceptive method they believe works best for them.     

Pulmonary disease caused by rapidly growing mycobacteria

The rapidly growing mycobacteria (RGM) differ from slow-growing mycobacteria such as Mycobacterium tuberculosis by virtue of their more rapid growth in culture media and their in vitro resistance to standard antituberculosis drugs. The RGM can produce numerous infections including chronic lung disease. The most common causes of pulmonary disease are Mycobacterium abscessus and Mycobacterium fortuitum. This article reviews the management of patients with lung disease caused by RGM.     

Differential mobilization of myeloma cells and normal hematopoietic stem cells in multiple myeloma after treatment with cyclophosphamide and granulocyte-macrophage colony-stimulating factor

Peripheral blood stem cells (PBSCs) mobilized with high-dose chemotherapy and hematopoietic growth factors are now widely used to support myeloablative therapy of multiple myeloma and effect complete remissions in up to 50% of patients with apparent extension of event- free and overall survival. Because tumor cells are present not only in bone marrow, but also in virtually all PBSC harvests, it is conceivable that autografted myeloma cells contribute to relapse after autotransplants. In this study, the kinetics of mobilization of normal hematopoietic stem cells were compared with those of myeloma cells present in PBSC harvests of 12 patients after high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor administration. CD34+ and CD34+Lin-Thy+ stem cell contents were measured by multiparameter flow cytometry, and myeloma cells were quantitated by immunostaining for the relevant Ig light chain and by a quantitative polymerase chain reaction for the myeloma-specific CDRIII sequence. Results indicated marked heterogeneity in the percentages of mobilized stem cells among different patients (0.1% to 22.2% for CD34+ cells and 0.1% to 7.5% for CD34+Lin-Thy+ cells, respectively). The highest proportions of hematopoietic progenitor cells were observed early during apheresis, with 9 of 12 patients mobilizing adequate amounts of CD34+ cells for 2 autotransplants (> 4 x 10(6)/kg) within the first 2 days, whereas peak levels (percent and absolute numbers) of myeloma cells were present on days 5 and 6 (0.5% to 22.0%). During the last days of collection, mobilized tumor cells exhibited more frequently high labeling index values (1% to 10%; median, 4.4%) and an immature phenotype (CD19+). The differential mobilization observed between normal hematopoietic stem cells and myeloma cells can be exploited to reduce tumor cell contamination in PBSC harvests.     

Follicular dendritic cells inhibit human B-lymphocyte proliferation.

In germinal centers, B lymphocytes are intimately associated with follicular dendritic cells (FDCs). It has been hypothesized that FDCs are involved in the regulation of B-cell growth and differentiation through cell-cell interactions. In this study, highly enriched preparations of FDCs were isolated by cell sorting using the FDC restricted monoclonal antibody DRC-1. When irradiated FDCs were cultured with mitogen stimulated B cells, B cell 3H-TdR uptake was inhibited by up to 80%. This inhibitory effect was not seen when paraformaldehyde fixed FDCs were added to B-cell cultures, suggesting that the FDCs needed to be metabolically active. Moreover, supernatants from cultured FDCs were similarly able to inhibit B-cell proliferation. These results demonstrate that FDCs may downregulate the clonal expansion of B cells that occurs within lymphoid follicles as part of the normal physiologic immune response. Potentially, the loss of the inhibitory role of FDCs in vivo may be of importance in certain infectious and neoplastic processes in which germinal centers are affected.     

Etoposide causes illegitimate V(D)J recombination in human lymphoid leukemic cells

Etoposide is one of the most widely used antineoplastics. Unfortunately, the same treatment schedules associated with impressive efficacy are associated with an increased risk of secondary acute myeloid leukemia (AML), which has prompted its withdrawal from some treatment regimens, thereby potentially compromising efficacy against the original tumor. Because etoposide-associated AML is characterized by site-specific illegitimate DNA recombination, we studied whether etoposide could directly cause site-specific deletions of exons 2 and 3 in the hprt gene. Human lymphoid CCRF-CEM cells were treated with etoposide for 4 hours, and DNA was isolated after subculturing. The deletion of exons 2 and 3 from hprt was assayed by a quantitative polymerase chain reaction (PCR) method. In the absence of etoposide treatment, the frequency of deletions of exons 2 and 3 was very low (5.05 x 10(-8)). After exposure to 10 mumol/ L etoposide, the frequency of the exon 2 + 3 deletion was increased immediately after and at 24 hours after etoposide treatment (65 to 89 x 10(-8)) and increased to higher levels (128 to 173 x 10(-8)) after 2 and 6 days of subculture (P < .001 overall). The frequency of the exon 2 + 3 deletion assessed at 6 days of subculture after 4 hours of 0, 0.25, 1, 2.5, 5, and 10 mumol/L etoposide treatment increased with etoposide concentration, ie, 5.05 x 10(-8), 89.2 x 10(-8), 108 x 10(-8), 142 x 10(-8), 163 x 10(-8), and 173 x 10(-8), respectively (P < .0001). Sequencing of a subset of amplified products confirmed the presence of DNA sequences at the breakpoints consistent with V(D)J recombination. By contrast, exon 2 + 3 deletions after etoposide treatment in the myeloid cell lines KG-1A and K562 showed no evidence of V(D)J recombinase in their genesis. We conclude that etoposide can induce the illegitimate site-specific action of V(D)J recombinase on an unnatural DNA substrate after a single treatment in human lymphoid cells.     

Nursing Now 2020: the Nightingale Challenge

Global healthcare expenditure is increasing, along with the numbers of older patients with multiple comorbidities, while the numbers of health workers are hugely decreasing, and many nursing and midwifery vacancies remain unfilled. With the World Health Organization declaring 2020 the Year of the Nurse and Midwife, and commencing the Nursing Now campaign with partners including the International Council of Nurses and the International Confederation of Midwives, has allowed these professions to unite, encourage advocacy and the call for global investment in nursing and midwifery. These actions will permit these professions to address universal health coverage, global inconsistencies of professional practice, and recruitment and retention. The Nightingale Challenge seeks to place early career nurses and midwives at the forefront of transformation, calling on employers worldwide to invest and provide nursing leadership development, and to become a key part of the solution to address the issues of providing universal health coverage, promoting gender equality and supporting economic growth. This will help place them at the heart of tackling 21st century health challenges.