Leptin Expression in Primary Trophoblast Cells in Response to Incubation with the Serum of Preeclamptic Women

Objective. We investigated whether the increase of leptin expression in preeclamptic placentas is additionally influenced by soluble maternal factors under hypoxic and nonhypoxic conditions. Methods. Term trophoblast cells were isolated and stimulated with sera from preeclamptic women under normoxic or hypoxic conditions. Levels of leptin mRNA and protein were evaluated by real-time RT-PCR or ELISA and Western blot analysis. Results. Leptin concentrations were increased in the serum of patients with preeclampsia and gestational diabetes. Hypoxia, insulin, and dexamethasone induced leptin expression in trophoblast cells. The incubation with sera from preeclamptic women led to a small, though, significant, increase of leptin gene expression. The effect of preeclamptic serum on leptin gene expression in trophoblast cells was lost under hypoxia. The serum of women with gestational diabetes did not increase leptin expression neither in normoxic nor hypoxic primary trophoblast cells. Conclusion. Our results can not exclude a soluble maternal factor in the serum of women with preeclampsia accounting for increased leptin expression in placental tissue in addition to hypoxia. However, an important biological role of this small increase in nonhypoxic conditions does not seem very likely.     

Cortical cerebral microinfarcts on 7T MRI: Risk factors,neuroimaging correlates and cognitive functioning – The Medea-7T study

We determined the occurrence and association of cortical cerebral microinfarcts (CMIs) at 7 T MRI with risk factors, neuroimaging markers of small and large vessel disease, and cognitive functioning. Within the Medea-7T study, a diverse cohort of older persons with normal cognition, patients with vascular disease, and memory clinic patients, we included 386 participants (68 ± 9 years) with available 7 T and 1.5 T/3T brain MRI, and risk factor and neuropsychological data. CMIs were found in 10% of participants and were associated with older age (RR = 1.79 per +10 years, 95%CI 1.28–2.50), history of stroke or TIA (RR = 4.03, 95%CI 2.18–7.43), cortical infarcts (RR = 5.28, 95%CI 2.91–9.55), lacunes (RR = 5.66, 95%CI 2.85–11.27), cerebellar infarcts (RR = 2.73, 95%CI 1.27–5.84) and decreased cerebral blood flow (RR = 1.35 per −100 ml/min, 95%CI 1.00–1.83), after adjustment for age and sex. Furthermore, participants with >2 CMIs had 0.5 SD (95%CI 0.05–0.91) lower global cognitive performance, compared to participants without CMIs. Our results indicate that CMIs on 7 T MRI are observed in vascular and memory clinic patients with similar frequency, and are associated with older age, history of stroke or TIA, other brain infarcts, and poorer global cognitive functioning.     

Shear Stress‐Induced Total Blood Trauma in Multiple Species

The common complications in heart failure patients with implanted ventricular assist devices (VADs) include hemolysis, thrombosis, and bleeding. These are linked to shear stress‐induced trauma to erythrocytes, platelets, and von Willebrand factor (vWF). Novel device designs are being developed to reduce the blood trauma, which will need to undergo in vitro and in vivo preclinical testing in large animal models such as cattle, sheep, and pig. To fully understand the impact of device design and enable translation of preclinical results, it is important to identify any potential species‐specific differences in the VAD‐associated common complications. Therefore, the purpose of this study was to evaluate the effects of shear stress on cells and proteins in bovine, ovine, and porcine blood compared to human. Blood from different species was subjected to various shear rates (0–8000/s) using a rheometer. It was then analyzed for complete blood counts, hemolysis by the Harboe assay, platelet activation by flow cytometry, vWF structure by immunoblotting, and function by collagen binding activity ELISA (vWF : CBA). Overall, increasing shear rate caused increased total blood trauma in all tested species. This analysis revealed species‐specific differences in shear‐induced hemolysis, platelet activation, and vWF structure and function. Compared to human blood, porcine blood was the most resilient and showed less hemolysis, similar blood counts, but less platelet activation and less vWF damage in response to shear. Compared to human blood, sheared bovine blood showed less hemolysis, similar blood cell counts, greater platelet activation, and similar degradation of vWF structure, but less impact on its activity in response to shear. The shear‐induced effect on ovine blood depended on whether the blood was collected via gravity at the abattoir or by venepuncture from live sheep. Overall, ovine abattoir blood was the least resilient in response to shear and bovine blood was the most similar to human blood. These results lay the foundations for developing blood trauma evaluation standards to enable the extrapolation of in vitro and in vivo animal data to predict safety and biocompatibility of blood‐handling medical devices in humans. We advise using ovine venepuncture blood instead of ovine abattoir blood due to the greater overall damage in the latter. We propose using bovine blood for total blood damage in vitro device evaluation but multiple species could be used to create a full understanding of the complication risk profile of new devices. Further, this study highlights that choice of antibody clone for evaluating platelet activation in bovine blood can influence the interpretation of results from different studies.     

Mobile app for treatment of stress urinary incontinence: A randomized controlled trial

Aims

To evaluate the effect of a mobile app treatment for stress urinary incontinence (SUI) in women.

Methods

Randomized controlled trial, conducted 2013‐2014 in Sweden. Community‐dwelling adult women with ≥1 SUI episode/week recruited through our website and randomized to app treatment (n = 62) or control group (postponed treatment, n = 61). One participant from each group was lost to follow‐up. Intervention was the mobile app Tät^® with a treatment program focused on pelvic floor muscle training (PFMT), and information about SUI and lifestyle factors. Primary outcomes, 3 months after randomization: symptom severity (International Consultation on Incontinence Modular Questionnaire Urinary Incontinence Short Form [ICIQ‐UI SF]); and condition‐specific quality of life (ICIQ Lower Urinary Tract Symptoms Quality of Life [ICIQ‐LUTSqol]).

Results

One hundred and twenty‐three women were included (mean age 44.7), with moderate/severe SUI (97.5%, 120/123), mean ICIQ‐UI SF score 11.1 (SD 2.8) and mean ICIQ‐LUTSqol score 34.4 (SD 6.1) at baseline. At follow‐up, the app group reported improvements in symptom severity (mean ICIQ‐UI SF score reduction: 3.9, 95% confidence interval 3.0‐4.7) and condition‐specific quality of life (mean ICIQ‐LUTSqol score reduction: 4.8, 3.4‐6.2) and the groups were significantly different (mean ICIQ‐UI SF score difference: ?3.2, ?4.3to ?2.1; mean ICIQ‐LUTSqol score difference: ?4.6, ?7.8 to ?1.4). In the app group, 98.4% (60/61) performed PFMT at follow‐up, and 41.0% (25/61) performed it daily.

Conclusions

The mobile app treatment was effective for women with SUI and yielded clinically relevant improvements. This app may increase access to first‐line treatment and adherence to PFMT.

     

Anti‐ACSA‐2 defines a novel monoclonal antibody for prospective isolation of living neonatal and adult astrocytes

Astrocytes are the most abundant cell type of the central nervous system and cover a broad range of functionalities. We report here the generation of a novel monoclonal antibody, anti‐astrocyte cell surface antigen‐2 (Anti‐ACSA‐2). Flow cytometry, immunohistochemistry and immunocytochemistry revealed that Anti‐ACSA‐2 reacted specifically with a not yet identified glycosylated surface molecule of murine astrocytes at all developmental stages. It did not show any labeling of non‐astroglial cells such as neurons, oligodendrocytes, NG2⁺ cells, microglia, endothelial cells, leukocytes, or erythrocytes. Co‐labeling studies of GLAST and ACSA‐2 showed largely overlapping expression. However, there were also notable differences in protein expression levels and frequencies of single‐positive subpopulations of cells in some regions of the CNS such as cerebellum, most prominently at early postnatal stages. In the neurogenic niches, the dentate gyrus of the hippocampus and the subventricular zone (SVZ), again a general overlap with slight differences in expression levels were observed. ACSA‐2 was unlike GLAST not sensitive to papain‐based tissue dissociation and allowed for a highly effective, acute, specific, and prospective purification of viable astrocytes based on a new rapid sorting procedure using Anti‐ACSA‐2 directly coupled to superparamagnetic MicroBeads. In conclusion, ACSA‐2 appears to be a new surface marker for astrocytes, radial glia, neural stem cells and bipotent glial progenitor cells which opens up the possibility of further dissecting the characteristics of astroglial subpopulations and lineages.     

Trabecular bone structure of the distal radius, the calcaneus, and the spine: which site predicts fracture status of the spine best?

RATIONALE AND OBJECTIVES: To compare trabecular bone structure measures obtained in magnetic resonance images of the distal radius and the calcaneus as well as computed tomographic images of the spine versus bone mineral density (BMD) of the spine and the calcaneus in the prediction of osteoporotic spine fracture status. MATERIAL AND METHODS: High-resolution magnetic resonance images of the calcaneus and the distal radius and thin-section computed tomographic images of thoracic and lumbar vertebrae were obtained from 74 cadavers. Structure analysis was performed using parameters analogous to standard histomorphometry. BMD of the spine was determined by using quantitative computed tomography and of the calcaneus by using dual x-ray absorptiometry. Spine radiographs of these cadavers were assessed concerning vertebral deformities. RESULTS: The diagnostic performance in differentiating fracture and nonfracture subjects was highest for structure parameters in the spine and slightly lower for these parameters in the distal radius and for BMD of the spine. CONCLUSION: In this study structure parameters in the spine were best suited to predict the osteoporotic fracture status of the spine.     

The stentless freestyle bioprosthesis: impact of age over 80 years on quality of life, perioperative, and mid-term outcome

Abstract Background: The steadily increasing life expectancy of the population in the Western World, together with the progress in noninvasive diagnostic methods and operating techniques lead to an increase in aortic valve surgery in elderly people. Aim of the study: Is there an increased risk of adverse perioperative and mid‐term outcome for octogenarians and do they benefit from aortic valve replacement (AVR) with stentless bioprostheses?Methods: Between 1996 and 2002, 503 patients older than 60 years underwent AVR with a stentless Freestyle bioprosthesis. Seventy‐six of them were older than 80 years. The risk of operative mortality, perioperative complications, valve‐related morbidity for octogenarians was determined by multivariate logistic regression. Results: In general, risk‐adjusted analyses did not reveal an increased risk of operative mortality (p = 0.4), postoperative atrial fibrillation (p = 0.2), prolonged ventilation (p = 0.5), prolonged stay in the intensive care unit (p = 0.3), or mid‐term valve‐related morbidity as prosthetic valve endocarditis (p = 0.2), reoperation (p = 0.4), bleeding events (p = 0.1), and stroke (p = 0.8) for octogenarians. Continuously increasing age was an independent risk factor for postoperative neurological complications (OR = 1.8 per 10 years, p = 0.04). Quality of life was equal to or better than the general population of the same age. Median survival time of octogenarians was 5.2 ± 0.5 years. Conclusions: Except for postoperative neurological complications, octogenarians receiving stentless bioprostheses had no increased risk of adverse perioperative and mid‐term outcome in comparison to younger patients. As quality of life and life expectancy after AVR with stentless valves were equal to the general population, AVR with stentless bioprostheses should not be withheld from octogenarians.     

Compression strapping: the development of a novel compression technique to enhance compression therapy and healing for 'hard-to-heal' leg ulcers

Non healing wounds of the lower limb continue to be a significant issue for both practitioners and patients. Failure of gold-standard management demands a creative response. This article describes the development of a novel and intuitive strapping technique overlying the compression bandage that appears to have an influence in healing complex lower limb ulcers. A retrospective audit of 17 patients with 25 ulcers allows further analysis and discussion. The strapping technique uses cohesive inelastic compression bandaging; narrow strips of bandages are layered in a fan distribution over the ulcer and oedema. This approach seems to offer an intuitive response to these complex wounds, allowing management to be tailored to the site of the ulcer and oedema. Tolerance for this less bulky compression therapy regime is excellent, thereby aiding healing and reducing all costs associated with non healing leg ulcers.     

Primary tumor dependent inhibition of tumor growth,angiogenesis, and perfusion of secondary breast cancer in bone

The systemic balance of angiogenic and anti‐angiogenic factors has been proposed to play a key‐role in primary tumor growth dependent growth suppression of secondary tumors. Despite the importance of the organ microenvironment to angiogenesis and microcirculation, the influence of a primary tumor on secondary bone tumors has not been investigated so far. Since breast cancer has a high propensity to spread to bone, we used an in vivo xenograft model to determine the impact of growing breast cancer cells (MCF‐7) in the mammary fat pad on the microvascular properties of subsequently inoculated secondary breast cancer tumors in bone. Mice were either treated with a resection of the primary tumor (n = 10) or no surgery (n = 9) and intravital microscopy was performed over 25 days in bone tumors. Tumor growth in bone was temporarily suppressed by the primary tumor on days 10 and 14. While microvascular permeability and vascular diameter decreased in both groups over time, the presence of the primary tumor was accompanied by a decreased tumor perfusion on days 8 and 10 through a reduction in vessels with diameters between 5 and 20 µm. The results imply a potential benefit of a therapeutic regime in which the resection of the primary tumor is combined with an anti‐angiogenic therapy in the perioperative or direct postoperative period. This might result in reduced progression of bone metastasis subsequent to excision of the primary tumor. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1251–1258, 2011