CD86+ or HLA-G+ can be transferred via trogocytosis from myeloma cells to T cells and are associated with poor prognosis

The transfer of membrane proteins between cells during contact, known as trogocytosis, can create novel cells with a unique phenotype and altered function. We demonstrate that trogocytosis is more common in multiple myeloma (MM) than chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia; that T cells are more probable to be recipients than B or natural killer cells; that trogocytosis occurs independently of either the T-cell receptor or HLA compatibility; and that after trogocytosis, T cells with acquired antigens can become novel regulators of T-cell proliferation. We screened 168 patients with MM and found that CD86 and human leukocyte antigen G (HLA-G) were antigens commonly acquired by T cells from malignant plasma cells. CD3(+)CD86(acq+) and CD3(+) HLA-G(acq+) cells were more prevalent in bone marrow than peripheral blood samples. The presence of either CD86 or HLA-G on malignant plasma cells was associated with a poor prognosis. CD38(++) side population cells expressed HLA-G, suggesting that these putative myeloma stem cells could generate immune tolerance. HLA-G(+) T cells had a regulatory potency similar to natural Tregs, thus providing another novel mechanism for MM to avoid effective immune surveillance.     

Specialist Palliative Care is More Than Drugs: A Retrospective Study of ILD Patients

Background  

This study aimed to assess the palliative care needs of progressive idiopathic fibrotic interstitial lung disease (PIF-ILD) populations in two London ILD centres.     

The effectiveness of early mobilization after tendon transfers in the hand: A systematic review

Study DesignSystematic review.IntroductionOver the past decade, early mobilization (initiated within a week) has become an increasing trend in postoperative rehabilitation after tendon transfer surgery in the hand. However, there are no published reviews summarizing the effectiveness of early mobilization protocols in comparison with conventional immobilization in tendon transfer rehabilitation.PurposeTo systematically review available evidence on the effectiveness of early mobilization protocols to conventional immobilization protocol after tendon transfers in the hand.MethodsA literature search of the Cochrane Library, PubMed, PEDro, EMBASE, and CINAHL databases was conducted (1980 to date). Randomized controlled trials (RCTs), case–control, and other study designs were included. Six articles were eligible for inclusion in the analysis (five RCTs and one retrospective study) and 260 articles that did not meet inclusion criteria were excluded. Level of evidence (Center for Evidence-based Medicine) and methodological quality (Structured Effectiveness Quality Evaluation Scale [SEQES] score) of each study were assessed by two independent reviewers.ResultsThis review found three high quality trials (SEQES score: 35–43 of 48), with level 1b and 2b evidence, supporting early mobilization of tendon transfers. The literature reports reduced total cost, total rehabilitation time, and demonstrates that early mobilization is a safe approach with no incidence of tendon ruptures or insertion pull out. In the initial phase of rehabilitation, outcomes like range of motion, grip strength, pinch strength, total active motion of digits, deformity correction, and tendon transfer integration were significantly superior with early mobilization compared with immobilization. However, in the long term, these outcomes were similar in both the groups, suggesting that early mobilization protocol improves hand function in the initial phase of rehabilitation (four weeks) and the long-term results (two months to one year) are equivalent to immobilization.ConclusionsBased on a limited number of small studies, there is evidence of short-term benefit for early mobilization, but inconclusive findings for longer-term outcomes. Until the body of evidence increases, clinicians should consider the clinical context, their experience in optimizing patient outcomes after surgery, and the patient's preferences when selecting between early and late mobilization after tendon transfer.Level of Evidence2a.     

Setting priorities in global child health research investments: assessment of principles and practice

This article reviews theoretical and practical approaches for setting priorities in global child health research investments. It also provides an overview of previous attempts to develop appropriate tools and methodologies to define priorities in health research investments. A brief review of the most important theoretical concepts that should govern priority setting processes is undertaken, showing how different perspectives, such as medical, economical, legal, ethical, social, political, rational, philosophical, stakeholder driven, and others will necessarily conflict each other in determining priorities. We specially address present research agenda in global child health today and how it relates to United Nation's (UN) Millennium Development Goal 4, which is to reduce child mortality by two-thirds between 1990 and 2015. The outcomes of these former approaches are evaluated and their benefits and shortcomings presented. The case for a new methodology for setting priorities in health research investments is presented, as proposed by Child Health and Nutrition Research Initiative, and a need for its implementation in global child health is outlined. A transdisciplinary approach is needed to address all the perspectives from which investments into health research can be seen as priorities. This prioritization requires a process that is transparent, systematic, and that would take into account many perspectives and build on advantages of previous approaches.     

Mammary gland development in early pubertal female macaques

Ductal morphogenesis of the mammary gland occurs largely in the early pubertal period under the influence of ovarian sex hormones. In this study we characterized developing ductal structures in breast tissue of 14 female prepubertal or early pubertal rhesus monkeys (average age, 2.6 +/- 0.1 years). Serum estradiol concentrations ranged from < 5.0 to 61.2 pg/ml, while progesterone concentrations were low in all animals (< 0.6 ng/ml). No corpora lutea were seen on ovarian histology. The most immature mammary glands contained multilayered ducts frequently ending in distinctive terminal end bud structures. Transitional ducts had variably stratified columnar epithelium, often with prominent rounded myoepithelial cells and loose periductal stroma. Mature ducts had simple cuboidal luminal epithelium, flattened myoepithelium, and associated lobular development, typical of the premenopausal breast. Expression of estrogen receptor alpha was significantly higher in immature ducts compared to mature ducts, while progesterone receptor expression, epithelial proliferation, and cytokeratin expression did not show a relationship to the maturity of the ducts. These findings identify dynamic morphologic changes occurring in the primate breast during early puberty and suggest that estradiol (rather than progesterone) is the predominant hormonal stimulus for early ductal and lobular development.