Kinetics of transfemoral amputees with osseointegrated fixation performing common activities of daily living

BACKGROUND: Direct anchorage of a lower-limb prosthesis to the bone through an implanted fixation (osseointegration) has been suggested as an excellent alternative for amputees experiencing complications from use of a conventional socket-type prosthesis. However, an attempt needs to be made to optimize the mechanical design of the fixation and refine the rehabilitation program. Understanding the load applied on the fixation is a crucial step towards this goal. METHODS: The load applied on the osseointegrated fixation of nine transfemoral amputees was measured using a load transducer, when the amputees performed activities which included straight-line level walking, ascending and descending stairs and a ramp as well as walking around a circle. Force and moment patterns along each gait cycle, magnitudes and time of occurrence of the local extrema of the load, as well as impulses were analysed. FINDINGS: Managing a ramp and stairs, and walking around a circle did not produce a significant increase (P>0.05) in load compared to straight-line level walking. The patterns of the moment about the medio-lateral axis were different among the six activities which may reflect the different strategies used in controlling the prosthetic knee joint. INTERPRETATIONS: This study increases the understanding of biomechanics of bone-anchored osseointegrated prostheses. The loading data provided will be useful in designing the osseointegrated fixation to increase the fatigue life and to refine the rehabilitation protocol.     

FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue

Adipogenesis is spatiotemporally coupled to angiogenesis throughout adult life, and the interplay between these two processes is communicated by multiple factors. Here we show that in a transgenic mouse model, increased expression of forkhead box C2 (FOXC2) in the adipose tissue affects angiogenesis, vascular patterning, and functions. White and brown adipose tissues contain a considerably high density of microvessels appearing as vascular plexuses, which show redistribution of vascular smooth muscle cells and pericytes. Dysfunction of these primitive vessels is reflected by impairment of skin wound healing. We further provide a mechanistic insight of the vascular phenotype by showing that FOXC2 controls Ang-2 expression by direct activation of its promoter in adipocytes. Remarkably, an Ang-2-specific antagonist almost completely reverses this vascular phenotype. Thus, the FOXC2-Ang-2 signaling system is crucial for controlling adipose vascular function, which is part of an adaptation to increased adipose tissue metabolism.     

Cysticercosis: cellular immune responses during primary and secondary infection

Immune reactions to cysticercosis have been extensively studied in mice. The lack of significant lymphocyte infiltration into the livers of infected mice and the obvious role of antibodies in rejection has led to the general conclusion that cellular reactions do not play a role in protection against this disease. In contrast, the present study examining the immune response to cestode infections in a large animal model (sheep) revealed the presence of a massive and highly organized cellular infiltration in the livers after a secondary Taenia hydatigena infection. The majority of the infiltrating lymphocytes were of the CD4+ phenotype with much fewer CD8+ cells present. While most gamma delta-TCR+ cells in peripheral blood are SBU-T19+, the majority of gamma delta-TCR+ lymphocytes in the liver lesions are SBU-T19- suggesting selective migration of these cells into the lesions. In contrast to the diffuse distribution of T cells in the lesions, B cells were present as distinct aggregates. In primary T. hydatigena infections, host class I and class II MHC antigens were shown, for the first time in cestode infections, to be absorbed onto the surface of the metacestode bladderwall indicating their possible involvement in parasite survival. No immune reactions were observed close to the parasite although lymphocytes and eosinophils were infiltrating the adjacent portal tract areas. Most lymphocytes in both primary and secondary infections were positive for MHC class II antigens suggesting selective recruitment of activated cells to the site of infection. Significant changes in relative and absolute numbers of lymphocyte subpopulations were also observed in the draining hepatic lymph nodes dominated by a massive increase of B cells. In contrast, at the peak of local cellular infiltration, no changes in lymphocyte subpopulations were observed in peripheral blood showing the limited usefulness of this compartment in studying cellular changes in localized infections. The vigorous cellular response observed in the livers of sheep contrasts sharply with the lack of lymphocyte infiltration reported in mice indicating that small animal models may not be appropriate to study cellular responses to cysticercosis in large animals and man.     

The efficacy of intranasal fluticasone propionate in the relief of ocular symptoms associated with seasonal allergic rhinitis.

Intranasal corticosteroids have been shown to decrease ocular symptoms associated with allergic rhinitis as well as nasal symptoms. The primary objective of this retrospective analysis was to evaluate the efficacy of fluticasone propionate (FP) aqueous nasal spray in the treatment of ocular symptoms in patients with seasonal allergic rhinitis (SAR). We pooled efficacy data from seven multicenter, randomized, double-blind, placebo-controlled studies of similar design. Each study evaluated the efficacy of intranasal FP, 200 micrograms, given once daily in the treatment of nasal and ocular symptoms associated with SAR. At baseline and after 7 and 14 days of treatment, clinicians rated the severity of four individual ocular symptoms (itching, tearing, redness, and puffiness) via visual analog scales of 0-100, where 0 = no symptoms and 100 = worst symptoms. The four ratings were added to form the total ocular symptom score (TOSS). Patients rated the overall severity of their ocular symptoms (all symptoms evaluated with a single score) daily on diary cards in a similar fashion. The primary outcome was the mean change from baseline in the clinician-rated TOSS. A between-group difference of 25 points in the mean change from baseline TOSS by day 14 was considered clinically relevant. The FP group had greater mean changes from baseline in the TOSS and in all four individual symptom scores compared with placebo at days 7 and 14. At day 7, mean decreases from baseline in the TOSS were 76.0 points for the FP group and 50.9 points for the placebo group (p < 0.001), a difference between groups of 25.1. At day 14, mean decreases from baseline in the TOSS were 91.8 points for the FP group and 60.2 points for the placebo group (p < 0.001), a difference between groups of 31.6. Consistent with the clinician-rated data, patient-rated data showed a significantly greater reduction in the overall ocular symptom score for the FP group compared with placebo for both weeks 1 and 2 (p < 0.001). Intranasal FP provides safe and effective relief of ocular symptoms associated with SAR. Patients with allergic rhinitis who also have ocular symptoms as a component of their disease may benefit from intranasal FP monotherapy without the addition of topical ophthalmologic agents or oral antihistamines. Such an approach may have advantages regarding compliance and cost-effectiveness of treatment.     

Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study

Obesity is a risk factor for colorectal cancer. Yet, some research indicates that weight-reducing bariatric surgery also increases colorectal cancer risk. Our study was undertaken because current evidence examining bariatric surgery and risk of colorectal cancer is limited and inconsistent. This population-based cohort study included adults with a documented obesity diagnosis in Denmark, Finland, Iceland, Norway or Sweden in 1980–2015. The incidence of colorectal cancer in participants with obesity who had and had not undergone bariatric surgery was compared to the incidence in the corresponding background population by calculating standardized incidence ratios (SIR) with 95% confidence intervals (CI). Additionally, operated and nonoperated participants with obesity were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs adjusted for confounders. Among 502,772 cohort participants with an obesity diagnosis, 49,931(9.9%) underwent bariatric surgery. The overall SIR of colon cancer was increased after bariatric surgery (SIR 1.56; 95% CI 1.28–1.88), with higher SIRs ≥10 years postsurgery. The overall HR of colon cancer in operated compared to nonoperated participants was 1.13 (95% CI 0.92–1.39) and 1.55 (95% CI 1.04–2.31) 10–14 years after bariatric surgery. Bariatric surgery did not significantly increase the risk of rectal cancer (SIR 1.14, 95% CI 0.83–1.52; HR 1.08, 95% CI 0.79–1.49), but the risk estimates increased with longer follow-up periods. Our study suggests that bariatric surgery is associated with an increased risk of colon cancer, while the support for an increased risk of rectal cancer was weaker.