Experimental Spinal Fusion With Recombinant Human Bone Morphogenetic Protein-2 Without Decortication of Osseous Elements

Study Design. L4-L5 intertransverse process fusions were produced with 58 μg, 230 μg, or 920 μg of recombinant human bone morphogenetic protein-2 in 20 dogs. Eleven had traditional decortication of posterior elements before insertion of the implant. Nine were left undecorticated. All animals were evaluated 3 months after surgery. Objectives. To determine whether decortication is a prerequisite for successful fusion in the presence of osteoinductive proteins such as bone morphogenetic protein-2. Summary of Background Data. Recombinant osteoinductive proteins can induce de novo bone in ectopic soft-tissue sites in the absence of bone marrow elements. Traditional methods for achieving spinal fusion rely on exposure of bone marrow through decortication to facilitate osteogenesis. It is hypothesized that the presence of an implanted osteoinductive protein obviates the need for exposure and release of host inductive factors. Methods. Recombinant human bone morphogenetic protein-2-induced intertransverse process fusions were performed with and without decortication. Fusion sites were evaluated by computed tomography imaging, high-resolution radiography, manual testing, mechanical testing, and histologic analysis. Results. One hundred percent of decorticated spines and 89% of undecorticated spines were clinically fused by 3 months. Ninety-one percent of decorticated spines and 78% of undecorticated specimens exhibited bilateral transverse process osseous bridging. The only spines that failed to achieve solid bilateral arthrodesis were in the lowest dose group. With the higher two doses, there was histologic evidence of osseous continuity between the fusion mass and undecorticated transverse processes. Conclusions. There were no statistical differences in clinical and radiographic fusion rates between decorticated and undecorticated sites. With higher doses of recombinant human bone morphogenetic protein-2, there was little histologic distinction between fusions in decorticated versus undecorticated spines

Effective Doses of Recombinant Human Bone Morphogenetic Protein-2 in Experimental Spinal Fusion

Study Design Nineteen dogs underwent L4-L5 intertransverse process fusions with either 58 μg, 115 μg, 230 μg, 460 μg, or 920 μg of recombinant human bone morphogenetic protein-2 carried by a polylactic acid polymer. A previous study (12 dogs) compared 2300 μg of recombinant human bone morphogenetic protein-2, autogenous iliac bone, and carrier alone in this model. All fusions subsequently were compared. Objectives To characterize the dose-response relationship of recombinant human bone morphogenetic protein-2 in a spinal fusion model. Summary of Background Data Recombinant osteoinductive morphogens, such as recombinant human bone morphogenetic protein-2, are effective in vertebrate diaphyseal defect and spinal fusion models. It is hypothesized that the quality of spinal fusion produced with recombinant human bone morphogenetic protein-2, above a threshold dose, does not change with increasing amounts of inductive protein. Methods After decortication of the posterior elements, the designated implants were placed along the intertransverse process space bilaterally. The fusion sites were evaluated after 3 months by computed tomography imaging, high-resolution radiography, manual testing, mechanical testing, and histologic analysis. Results As in the study using 2300 μg of recombinant human bone morphogenetic protein-2, implantation of 58–920 μg of recombinant human bone morphogenetic protein-2 successfully resulted in intertransverse process fusion in the dog by 3 months. This had not occurred in animals containing autograft or carrier alone. The cross-sectional area of the fusion mass and mechanical stiffness of the L4-L5 intersegment were not dose-dependent. Histologic findings varied but were not related to rhBMP-2 dose. Inflammatory reaction to the composite implant was proportional inversely to the volume of the fusion mass. Conclusions No mechanical, radiographic, or histologic differences in the quality of intertransverse process fusion resulted from a 40-fold variation in dose of recombinant human bone morphogenetic protein-2

Intervention psychosociale auprès des personnes infectées par le VIH

Nous décrivons ici un programme d'intervention psychosociale conçu pour mieux traiter le stress associé à l'infection du VIH. Le programme d'intervention NUCARE se fonde sur six composantes : restructuration cognitive, résolution de problèmes, relaxation, détermination d'objectifs, soutien social et utilisation de ressources et de services. Nous décrivons ici la logique et le développement de l'intervention, et présentons des exemples concrets pour illustrer les avantages de chacune de ses composantes.We describe a psychosocial intervention program designed to enhance coping with the stress associated with HIV infection. The NUCARE intervention program is based on six components of coping including: cognitive refraining, problem-solving, relaxation, goal setting, social support and use of resources and services. The rationale and development of the intervention is discussed and practical case examples illustrating the benefits of each component are presented

Photochemical Synthesis of the Bioconjugate Folic Acid-Gold Nanoparticles

In this paper we present a rapid and simple onepot method to obtain gold nanoparticles functionalized with folic acid using a photochemistry method. The bioconjugate folic acid-gold nanoparticle was generated in one step using a photo-reduction method, mixing hydrogen tetrachloroaurate with folic acid in different ratios and varying the illumination time of a mercury lamp (λ= 255 nm). Scanning electron microscopy showed a particle size of around 40-50nm and dynamic light scattering exhibited that the zeta potential varies from -41 to -50mV with different illumination times. Storage in the dark at 4°C prolongs the stability of folic acid-gold nanoparticle suspensions to up to 26 days. Ultraviolet visible and Fourier transform infrared spectroscopy showed a surface plasmon band of around 534nm and fluorescence spectroscopy exhibited a quenching effect on gold nanoparticles in the fluorescence emission of folic acid and thus confirmed the conjugation of folic acid to the surface of gold nanoparticles. In this study we demonstrate the use of a photochemistry method to obtain folic acid-gold nanoparticles in a simple and rapid way without the use of surfactants and long reaction times. The photochemical synthesis of FA-AuNPs opens new perspectives for creating novel functional nanomaterials for biomedical applications

Attitudes Toward Breast Cancer Genetic Testing in Five Special Population Groups

Purpose: This study examined interest in and attitudes toward genetic testing in 5 different population groups. Methods: The survey included African American, Asian American, Latina, Native American, and Appalachian women with varying familial histories of breast cancer. A total of 49 women were interviewed in person. Descriptive and nonparametric statistical techniques were used to assess ethnic group differences. Results: Overall, interest in testing was high. All groups endorsed more benefits than risks. There were group differences regarding endorsement of specific benefits and risks: testing to “follow doctor recommendations” (p=0.017), “concern for effects on family” (p=0.044), “distrust of modern medicine” (p=0.036), “cost” (p=0.025), and “concerns about communication of results to others” (p=0.032). There was a significant inverse relationship between interest and genetic testing cost (p Conclusion: Cost may be an important barrier to obtaining genetic testing services, and participants would benefit by genetic counseling that incorporates the unique cultural values and beliefs of each group to create an individualized, culturally competent program. Further research about attitudes toward genetic testing is needed among Asian Americans, Native Americans, and Appalachians for whom data are severely lacking. Future study of the different Latina perceptions toward genetic testing are encouraged

The Placenta-A New Source of Bile Acids during Healthy Pregnancy? First Results of a Gene Expression Study in Humans and Mice.

Bile acids (BAs) are natural ligands for several receptors modulating cell activities. BAs are synthesized via the classic (neutral) and alternative (acidic) pathways. The classic pathway is initiated by CYP7A1/Cyp7a1, converting cholesterol to 7α-hydroxycholesterol, while the alternative pathway starts with hydroxylation of the cholesterol side chain, producing an oxysterol. In addition to originating from the liver, BAs are reported to be synthesized in the brain. We aimed at determining if the placenta potentially represents an extrahepatic source of BAs. Therefore, the mRNAs coding for selected enzymes involved in the hepatic BA synthesis machinery were screened in human term and CD1 mouse late gestation placentas from healthy pregnancies. Additionally, data from murine placenta and brain tissue were compared to determine whether the BA synthetic machinery is comparable in these organs. We found that CYP7A1, CYP46A1, and BAAT mRNAs are lacking in the human placenta, while corresponding homologs were detected in the murine placenta. Conversely, Cyp8b1 and Hsd17b1 mRNAs were undetected in the murine placenta, but these enzymes were found in the human placenta. CYP39A1/Cyp39a1 and cholesterol 25-hydroxylase (CH25H/Ch25h) mRNA expression were detected in the placentas of both species. When comparing murine placentas and brains, Cyp8b1 and Hsd17b1 mRNAs were only detected in the brain. We conclude that BA synthesis-related genes are placentally expressed in a species-specific manner. The potential placentally synthesized BAs could serve as endocrine and autocrine stimuli, which may play a role in fetoplacental growth and adaptation

Increased risk of blood transfusion in patients with diabetes mellitus sustaining non-major burn injury

Background: Due to the increased mortality and morbidity associated with blood transfusion, identifying modifiable predictors of transfusion are vital to prevent or minimise blood use. We hypothesised that burn patients with diabetes mellitus were more likely to be prescribed a transfusion. These patients tend to have increased age, number of comorbidities, infection risk and need for surgery which are all factors reported previously to be associated with blood use. Objective: To determine whether patients with diabetes mellitus who have sustained a burn ≤20% total body surface area (TBSA) are at higher risk of receiving red blood cell transfusion compared to those without diabetes mellitus. Method: This was a retrospective cohort study including patients admitted to the major Burns Unit in Western Australia for management of a burn injury. Only the first hospital admission between May 2008 to February 2017 were included. Results: Among 2,101 patients with burn injuries ≤20% TBSA, 48 (2.3%) received packed red blood cells and 169 (8.0%) had diabetes. There were 13 (7.7%) diabetic patients that were transfused versus 35 (1.8%) non-diabetic patients. Patients with diabetes were 5.2 (p=0.034) times more likely to receive packed red blood cells after adjusting for percentage TBSA, haemoglobin at admission or prior to transfusion, number of surgeries, total comorbid burden and incidence of infection. As percentage TBSA increases, the probability of packed red blood cell transfusion increases at a higher rate in DM patients. Conclusions: This study showed that diabetic patients with burn injuries ≤20% TBSA have a higher probability of receiving packed red blood cell transfusion compared to patients without diabetes. This effect was compounded in burns with higher percentage TBSA

Including random centre effects in design, analysis and presentation of multi-centre trials.

BACKGROUND: In large multicentre trials in diverse settings, there is uncertainty about the need to adjust for centre variation in design and analysis. A key distinction is the difference between variation in outcome (independent of treatment) and variation in treatment effect. Through re-analysis of the CRASH-2 trial (2010), this study clarifies when and how to use multi-level models for multicentre studies with binary outcomes. METHODS: CRASH-2 randomised 20,127 trauma patients across 271 centres and 40 countries to either single-dose tranexamic acid or identical placebo, with all-cause death at 4 weeks the primary outcome. The trial data had a hierarchical structure, with patients nested in hospitals which in turn are nested within countries. Reanalysis of CRASH-2 trial data assessed treatment effect and both patient and centre level baseline covariates as fixed effects in logistic regression models. Random effects were included to assess where there was variation between countries, and between centres within countries, both in underlying risk of death and in treatment effect. RESULTS: In CRASH-2, there was significant variation between countries and between centres in death at 4 weeks, but absolutely no differences between countries or centres in the effect of treatment. Average treatment effect was not altered after accounting for centre and country variation in this study. CONCLUSIONS: It is important to distinguish between underlying variation in outcomes and variation in treatment effects; the former is common but the latter is not. Stratifying randomisation by centre overcomes many statistical problems and including random intercepts in analysis may increase power and decrease bias in mean and standard error estimates. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86750102 , ClinicalTrials.gov NCT00375258 , and South African Clinical Trial Register DOH-27-0607-1919

Shape matters: effects of silver nanospheres and wires on human alveolar epithelial cells

<p>Abstract</p> <p>Background</p> <p>In nanotoxicology, the exact role of particle shape, in relation to the composition, on the capacity to induce toxicity is largely unknown. We investigated the toxic and immunotoxic effects of silver wires (length: 1.5 - 25 μm; diameter 100 - 160 nm), spherical silver nanoparticles (30 nm) and silver microparticles (<45 μm) on alveolar epithelial cells (A549).</p> <p>Methods</p> <p>Wires and nanoparticles were synthesized by wet-chemistry methods and extensively characterized. Cell viability and cytotoxicity were assessed and potential immunotoxic effects were investigated. To compare the effects on an activated and a resting immune system, cells were stimulated with rhTNF-α or left untreated. Changes in intracellular free calcium levels were determined using calcium imaging. Finally, ion release from the particles was assessed by ICP-MS and the effects of released ions on cell viability and cytotoxicity were tested.</p> <p>Results</p> <p>No effects were observed for the spherical particles, whereas the silver wires significantly reduced cell viability and increased LDH release from A549 cells. Cytokine promoter induction and NF-κB activation decreased in a concentration dependent manner similar to the decrease seen in cell viability. In addition, a strong increase of intracellular calcium levels within minutes after addition of wires was observed. This toxicity was not due to free silver ions, since the samples with the highest ion release did not induce toxicity and ion release control experiments with cells treated with pre-incubated medium did not show any effects either.</p> <p>Conclusions</p> <p>These data showed that silver wires strongly affect the alveolar epithelial cells, whereas spherical silver particles had no effect. This supports the hypothesis that shape is one of the important factors that determine particle toxicity.</p

Men and Women in Space: Bone Loss and Kidney Stone Risk after Long-Duration Space Flight

Bone loss on Earth is more prevalent in women than men, leading to the assumption that women may be at greater risk from bone loss during flight. Until recently, the number of women having flown long-duration missions was too small to allow any type of statistical analysis. We report here data from 42 astronauts on long-duration missions to the International Space Station, 33 men and 9 women. Bone mineral density (dual-energy X-ray absorptiometry), bone biochemistry (from blood and urine samples), and renal stone risk factors were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. The response of bone mineral density to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an Advanced Resistive Exercise Device. Bone biochemistry, specifically markers of formation and resorption, generally responded similarly in male and female astronauts. The response of urinary supersaturation risk to space flight was not significantly different between men and women, although risks were typically increased after flight in both groups and risks were generally greater in men than in women before and after flight. Overall, the bone and renal stone responses of men and women to space flight were not different