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We aimed to describe the analgesic efficacy, duration of analgesia, and adverse event profile associated with intranasal hydromorphone in children with acute pain presenting to an emergency department.Prospective dose titration pilot study of otherwise healthy children 4 to 17-years-old with moderate to severe pain who required a parenteral opioid. All patients received an initial intranasal hydromorophone dose of 0.03 mg/kg. The need for additional analgesia was assessed at 15 and 30 min; an additional 0.015 mg/kg was given at each assessment, if required. Need for rescue analgesic, pain intensity and adverse events were assessed until 6 h after hydromorphone administration or until patients were discharged, underwent a procedure to treat their painful condition, or received a rescue analgesic.We enrolled 35 children. Fifteen, 11, and 9 children required a total dose of 0.03, 0.045, and 0.06 mg/kg, respectively. Patients in each dose group experienced an absolute decrease in pain score of ≥3/10 and percent reduction40% within 5-15 min of completing dose-titration administration of hydromorphone. Duration of analgesia (i.e. time until rescue analgesic administered)1 h was observed in 85.7% of patients. Patients not requiring rescue analgesics had mild or no pain until discharged or their painful conditions were treated. Three (8.6%) patients required a rescue analgesic1 h after hydromorphone administration. There were no major adverse events.Intranasal hydromorphone led to rapid, clinically significant and frequently sustained decreases in pain intensity in children. No major adverse events were observed in this preliminary sample. Clinical Trials Registration Number: NCT02437669.

Background Non-communicable diseases (NCD) account for a growing burden of morbidity and mortality in sub-Saharan Africa. Chronic lung disease is an important contributor to the NCD epidemic in this region but reliable burden of disease estimates are lacking. Aims and Objectives: We conducted a Burden of Obstructive Lung Disease (BOLD) study as part of the Blantyre Health Study in Malawi to assess the burden of non-communicable lung disease and other NCDs in this setting. Methods: We used GPS-enabled PDAs to collect data from all consenting adults (n=16079) living in the Chilomoni area of Blantyre. We took a population representative gender stratified random sample of 1000 adults aged 40 and above and visited them at home to conduct questionnaires and post bronchodilator spirometry to BOLD protocol requirements. Results: Full questionnaire and spirometry data were obtained from 600 participants of whom 413 (165 Male and 248 female) had post bronchodilator spirometry that met BOLD quality standards. Of these 5.9% of men and 9.3% of women had LLN Modified Stage 1 or higher COPD. 8% and 25% of men and 1% and 3% of women were current and ever smokers respectively. Use of biomass fuel or kerosene for cooking was universal. Age (OR 1.5/10yrs), female gender (OR 4.3) and current smoking (OR 3.74) were associated with an increased risk of COPD. Conclusions: Chronic lung disease is an important NCD in urban Malawi. Exposure to tobacco smoke is common in men; exposure to dirty burning fuels for cooking is universal amongst women. Targeted public health strategies are needed to tackle the prevention and management of non communicable chronic lung disease in Malawi and the sub Saharan African region.

This guide is a summary reference on the rehabilitation principles that should be applied in the treatment and prevention of osteoporosis. As this guide addresses primarily rehabilitation issues required by osteoporotic fracture or low bone mass, the health professional is directed to the National Osteoporosis Foundation’s companion piece, Physician’s Guide to Prevention and Treatment of Osteoporosis (‘Physician’s Guide’), for other treatment approaches. Rehabilitation and exercise are often viewed as a means to improve function, such as activities of daily living (ADL) for patients. Psychosocial factors also impact strongly on functional ability and the general health of the osteoporotic patient. The information in this guide is based on scientific evidence from basic research, consensus from an expert panel convened by the National Osteoporosis Foundation (NOF), clinical studies, and randomized controlled clinical trials. The small number of randomized trials points to the need for more of them in the future. The majority of the studies on rehabilitation approaches and exercise recommendations related to osteoporosis are based on studies among white perimenopausal women. Clearly, osteoporosis affects men and non-white women as well. It can also affect younger as well as older individuals with certain chronic conditions and medication use. Until we have additional data, recommendations for these other populations should be on an individual basis. The committee believes that the guidelines have universal application in terms of recommending life-long, safe activities and exercises for all people. This guide’s recommendations are not intended as rigid standards of practice, but must be tailored for use by physicians in consultation with their patients. Executive Summary

A potential treatment modality for joint pain due to cartilage degradation is electromagnetic fields (EMF) that can be delivered, noninvasively, to chondrocytes buried within cartilage. A pulsed EMF in clinical use for recalcitrant bone fracture healing has been modified to be delivered as a pulsed electric field (PEF) through capacitive coupling. It was the objective of this study to determine whether the PEF signal could have a direct effect on chondrocytes in vitro. This study shows that a 30-min PEF treatment can increase DNA content of chondrocyte monolayer by approximately 150% at 72 h poststimulus. Studies intended to explore the biological mechanism showed this PEF signal increased nitric oxide measured in culture medium and cGMP measured in cell extract within the 30-min exposure period. Increasing calcium in the culture media or adding the calcium ionophore A23187, without PEF treatment, also significantly increased short-term nitric oxide production. The inhibitor W7, which blocks calcium/calmodulin, prevented the PEF-stimulated increase in both nitric oxide and cGMP. The inhibitor L-NAME, which blocks nitric oxide synthase, prevented the PEF-stimulated increase in nitric oxide, cGMP, and DNA content. An inhibitor of guanylate cyclase (LY83583) blocked the PEF-stimulated increase in cGMP and DNA content. A nitric oxide donor, when present for only 30 min, increased DNA content 72 h later. Taken together, these results suggest the transduction pathway for PEF-stimulated chondrocyte proliferation involves nitric oxide and the production of nitric oxide may be the result of a cascade that involves calcium, calmodulin, and cGMP production.

As cell therapies advance from research laboratories to clinical application, there is the need to transport cells and tissues across long distances while maintaining cell viability and function. Currently cells are successfully stored and shipped under liquid nitrogen vapor. The ability to store these cells in the desiccated state at ambient temperature would provide tremendous economic and practical advantage. Human mesenchymal stem cells (hMSCs) have broad potential uses in tissue engineering and regeneration since they can differentiate along multiple lineages and support hematopoeisis. The current research applied recent technological advances in the dehydration and storage of human fibroblasts to hMSCs. Three conditions were tested: air-dried, air-dried and stored under vacuum (vacuum only), and incubated with 50 mM trehalose + 3% glycerol and then air-dried and stored under vacuum (vacuum + trehalose). Plates containing dehydrated hMSCs were shipped from San Diego to Baltimore overnight in separate FedEx cardboard boxes. The hMSCs were rehydrated with 3 ml of hMSC medium and were able to regain their spindle-shaped morphology and adhesive capability. In addition, they maintained high viability and proliferation capacity. Rehydrated and passaged cells continued to express the characteristic hMSC surface antigen panel. Additionally, cells showed constitutive levels of mRNA for a stromal factor and, when exposed to reagents known to induce differentiation, demonstrated upregulation of two tissue-specific messages indicative of differentiation potential for fat and bone. While our preliminary findings are encouraging, we still need to address consistency and duration of storage by considering factors such as cell water content, oxygen concentration, and the presence of free radicals.

This investigation tested the hypothesis that delivering mesenchymal stem cell-seeded implants to a tendon gap model results in significantly improved repair biomechanics. Cultured, autologous, marrow-derived mesenchymal stem cells were suspended in a collagen gel delivery vehicle; the cell-gel composite was subsequently contracted onto a pretensioned suture. The resulting tissue prosthesis was then implanted into a 1-cm-long gap defect in the rabbit Achilles tendon. Identical procedures were performed on the contralateral tendon, but only the suture material was implanted. The tendon-implant constructs were evaluated 4, 8, and 12 weeks later by biomechanical and histological criteria. Significantly greater load-related structural and material properties were seen at all time intervals in the mesenchymal stem cell-treated tendons than in the contralateral, treated control repairs (p < 0.05), which contained suture alone with natural cell recruitment. The values were typically twice those for the control tissues at each time interval. Load-related material properties for the treated tissues also increased significantly over time (p < 0.05). The treated tissues had a significantly larger cross-sectional area (p < 0.05), and their collagen fibers appeared to be better aligned than those in the matched controls. The results indicate that delivering mesenchymal stem cell-contracted, organized collagen implants to large tendon defects can significantly improve the biomechanics, structure, and probably the function of the tendon after injury.

Prolonged bed rest, undertaken by volunteers or resulting from injury and disease, can impair bone and muscle function and structure; extended travel in space also induces these effects. Fluid shifts and disrupted fluid balance may also contribute to observed musculoskeletal aberrations in the weightless environment. Some molecular and cellular events involved in the loading and unloading of the musculoskeletal system are under neural and endocrine influence or control, whereas other events are influenced by local growth factors. Studies are in progress to develop interventions that preserve or improve musculoskeletal integrity in 1g. The NIAMS and NASA are interested in basic and clinical studies of the influence of microgravity on the musculoskeletal system. The interagency workshop results form the basis for new collaborative and cooperative research emphases for the biomedical community under a broad agreement between the National Institutes of Health and NASA.

Osteoporosis, a condition in which bone mass is low, represents a major public health problem in developed societies. It may affect as many as 20 to 25 million people in the United States, and it is responsible for 1.3 million fractures each year, typically fractures of the spine, wrist, and hip. Osteoporosis exacts an enormous toll in morbidity and mortality, and its cost in the United States has been estimated at 7 to 10 billion dollars in 1986 alone. Predominantly, but not exclusively, osteoporosis is a disorder of women. The frequency of osteoporosis and osteoporosis-related fractures is expected to increase, because the most susceptible population—the elderly—is expanding.

Many factors determine the scientific merit of an NIH research grant application. This paper is intended to help optimize the organization and logical development of investigators' research ideas so that grant applications will be evaluated by the reviewers in as favorable a light as possible. The ingredients of a successful grant application are good ideas, good science, and a good application. The research should be based on a significant hypothesis and, if possible, oriented towards uncovering an important biological mechanism. Specific methods should be directly related to each aim of the project. Likewise, the specific aims should be related to each hypothesis. All aspects of the application should be clear and focused. It is best to define all assumptions, limitations, and alternative approaches. In general, the best philosophy is for the applicant to address all possible problems before the reviewers do.