Computer aided design and finite element modeling to predict bulk mechanical properties of bone scaffolds using triply periodic minimal surfaces (progettazione assistita al calcolatore ed analisi con il metodo degli elementi finiti per predire il comportamento meccanico di scaffolds ossei creati con l'uso di superfici minime periodiche in tre direzioni)

The aim of Tissue Engineering is to develop biological substitutes that will restore lost morphological and functional features of diseased or damaged portions of organs. Recently computer-aided technology has received considerable attention in the area of tissue engineering and the advance of additive manufacture (AM) techniques has significantly improved control over the pore network architecture of tissue engineering scaffolds. To regenerate tissues more efficiently, an ideal scaffold should have appropriate porosity and pore structure. More sophisticated porous configurations with higher architectures of the pore network and scaffolding structures that mimic the intricate architecture and complexity of native organs and tissues are then required. This study adopts a macro-structural shape design approach to the production of open porous materials (Titanium foams), which utilizes spatial periodicity as a simple way to generate the models. From among various pore architectures which have been studied, this work simulated pore structure by triply-periodic minimal surfaces (TPMS) for the construction of tissue engineering scaffolds. TPMS are shown to be a versatile source of biomorphic scaffold design. A set of tissue scaffolds using the TPMS-based unit cell libraries was designed. TPMS-based Titanium foams were meant to be printed three dimensional with the relative predicted geometry, microstructure and consequently mechanical properties. Trough a finite element analysis (FEA) the mechanical properties of the designed scaffolds were determined in compression and analyzed in terms of their porosity and assemblies of unit cells. The purpose of this work was to investigate the mechanical performance of TPMS models trying to understand the best compromise between mechanical and geometrical requirements of the scaffolds. The intention was to predict the structural modulus in open porous materials via structural design of interconnected three-dimensional lattices, hence optimising geometrical properties. With the aid of FEA results, it is expected that the effective mechanical properties for the TPMS-based scaffold units can be used to design optimized scaffolds for tissue engineering applications. Regardless of the influence of fabrication method, it is desirable to calculate scaffold properties so that the effect of these properties on tissue regeneration may be better understood.

Three-dimensional electron microscopy of myriapod hemocyanin, planorbid snail acetylcholine-binding protein and cyanobacterial Vipp1

Three-dimensional electron microscopy (3-D EM) provides a framework for the analysis of large protein quaternary structures. The advantage over the generally higher resolving meth- od of X-ray crystallography is the embedding of the proteins in their physiological environ- ment. However, results of the two methods can be combined to obtain superior structural information. In this work, three different protein types – (i) Myriapod hemocyanin, (ii) vesi- cle-inducing protein in plastids 1 (Vipp1) and (iii) acetylcholine-binding protein (AChBP) – were structurally analyzed by 2-D and 3-D EM and, where possible, functionally interpreted.rnMyriapod hemocyanins have been previously shown to be 6x6-meric assemblies that, in case of Scutigera coleoptrata hemocyanin (ScoHc), show two 3x6-mer planes whith a stag- gering angle of approximately 60°. Here, previously observed structural differences between oxy- and deoxy-ScoHc could be substantiated. A 4° rotation between hexamers of two dif- ferent 3x6-mer planes was measured, which originates at the most central inter-hexamer in- terface. Further information about allosteric behaviour in myriapod hemocyanin was gained by analyzing Polydesmus angustus hemocyanin (PanHc), which shows a stable 3x6-mer and divergent histidine patterns in the inter-hexamer interfaces when compared to ScoHc. Both findings would conclusively explain the very different oxygen binding properties of chilopod and diplopod hemocyanin.rnVipp1 is a protein found in cyanobacteria and higher plants which is essential for thyla- koid membrane function and forms highly variable ring-shaped structures. In the course of this study, the first 3-D analysis of Vipp1 was conducted and yielded reconstructions of six differently sized Vipp1 rings from negatively stained images at resolutions between 20 to 30 Å. Furthermore, mutational analyses identified specific N-terminal amino acids that are essential for ring formation. On the basis of these analyses and previously published results, a hypothetical model of the Vipp1 tertiary and quaternary structure was generated.rnAChBP is a water-soluble protein in the hemolymph of mollusks. It is a structural and functional homologue of the ligand-binding domain of nicotinic acetylcholine receptors. For the freshwater snail Biomphalaria glabrata, we previously described two types of AChBP (BgAChBP1 and BgAChBP2). In this work, a 6 Å 3-D reconstruction of native BgAChBP is presented, which shows a dodecahedral assembly that is unprecedented for an AChBP. Single particle analysis of recombinantely expressed BgAChBP types led to preliminary results show- ing a dodecahedral assembly of BgAChBP1 and a dipentameric assembly of BgAChBP2. This indicates divergent biological functions of the two types.

Simultaneous bilateral hip replacement reveals superior outcome and fewer complications than two-stage procedures: a prospective study including 1819 patients and 5801 follow-ups from a total joint replacement registry

Background Total joint replacements represent a considerable part of day-to-day orthopaedic routine and a substantial proportion of patients undergoing unilateral total hip arthroplasty require a contralateral treatment after the first operation. This report compares complications and functional outcome of simultaneous versus early and delayed two-stage bilateral THA over a five-year follow-up period. Methods The study is a post hoc analysis of prospectively collected data in the framework of the European IDES hip registry. The database query resulted in 1819 patients with 5801 follow-ups treated with bilateral THA between 1965 and 2002. According to the timing of the two operations the sample was divided into three groups: I) 247 patients with simultaneous bilateral THA, II) 737 patients with two-stage bilateral THA within six months, III) 835 patients with two-stage bilateral THA between six months and five years. Results Whereas postoperative hip pain and flexion did not differ between the groups, the best walking capacity was observed in group I and the worst in group III. The rate of intraoperative complications in the first group was comparable to that of the second. The frequency of postoperative local and systemic complication in group I was the lowest of the three groups. The highest rate of complications was observed in group III. Conclusions From the point of view of possible intra- and postoperative complications, one-stage bilateral THA is equally safe or safer than two-stage interventions. Additionally, from an outcome perspective the one-stage procedure can be considered to be advantageous.

The association between early hemodynamic variables and outcome in normothermic comatose patients following cardiac arrest

Currently, few data exist on the association between post-cardiac arrest hemodynamic function and outcome. In this explorative, retrospective analysis, the association between hemodynamic variables during the first 24 h after intensive care unit admission and functional outcome at day 28 was evaluated in 153 normothermic comatose patients following a cardiac arrest.

Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall

The human airway epithelium serves as structural and functional barrier against inhaled particulate antigen. Previously, we demonstrated in an in vitro epithelial barrier model that monocyte derived dendritic cells (MDDC) and monocyte derived macrophages (MDM) take up particulate antigen by building a trans-epithelial interacting network. Although the epithelial tight junction (TJ) belt was penetrated by processes of MDDC and MDM, the integrity of the epithelium was not affected. These results brought up two main questions: (1) Do MDM and MDDC exchange particles? (2) Are those cells expressing TJ proteins, which are believed to interact with the TJ belt of the epithelium to preserve the epithelial integrity? The expression of TJ and adherens junction (AJ) mRNA and proteins in MDM and MDDC monocultures was determined by RT-PCR, and immunofluorescence, respectively. Particle uptake and exchange was quantified by flow cytometry and laser scanning microscopy in co-cultures of MDM and MDDC exposed to polystyrene particles (1 μm in diameter). MDM and MDDC constantly expressed TJ and AJ mRNA and proteins. Flow cytometry analysis of MDM and MDDC co-cultures showed increased particle uptake in MDDC while MDM lost particles over time. Quantitative analysis revealed significantly higher particle uptake by MDDC in co-cultures of epithelial cells with MDM and MDDC present, compared to co-cultures containing only epithelial cells and MDDC. We conclude from these findings that MDM and MDDC express TJ and AJ proteins which could help to preserve the epithelial integrity during particle uptake and exchange across the lung epithelium.

Prosthetic Rehabilitation, Implant Survival and Quality of Life 2 to 5 Years after Resection of Oral Tumors

Background: After oral tumor resection, structural and functional rehabilitation by means of dental prostheses is complex, and positive treatment outcome is not always predictable. Purpose: The objective of the study was to report on oral rehabilitation and quality of life 2-5 years after resection of malignant oral tumors. Materials and Methods: Data of 46 patients (57 ± 7 years) who underwent oral tumor surgery were available. More than 50% of tumors were classified T3 or T4. Open oro-nasal defects resulted in 12 patients and full mandibulary block resections in 23 patients. Comprehensive planning, implant placement, and prosthetic rehabilitation followed an interdisciplinary protocol. Analysis comprised tumor location, type of prostheses, implant survival, and quality of life. Results: Because of advanced tumor status, resections resulted in marked alteration of the oral anatomy requiring complex treatment procedures. Prosthetic rehabilitation comprised fixed and removable prostheses, with 104 implants placed in 28 patients (60%). Early implant loss was high (13%) and cumulative survival rate of loaded implants was <90% after 5 years. Prosthetic plans had to be modified because of side effects of tumor therapy, complications with implants and tumor recurrence. The majority of patients rated quality of life favorable, but some experienced impaired swallowing, dry mouth, limited mouth opening, appearance, and soreness. Conclusions: Some local effects of tumor therapy could not be significantly improved by prosthetic rehabilitation leading to functional and emotional disability. Many patients had passed away or felt too ill to fill the questionnaires. This case series confirms the complex anatomic alterations after tumor resection and the need for individual treatment approaches especially regarding prosthesis design. In spite of disease-related local and general restrictions, most patients gave a positive assessment of quality of life.

Development of a novel fMRI compatible visual perception prototype battery to test older people with and without dementia

Background: Visuoperceptual deficits in dementia are common and can reduce quality of life. Testing of visuoperceptual function is often confounded by impairments in other cognitive domains and motor dysfunction. We aimed to develop, pilot, and test a novel visuocognitive prototype test battery which addressed these issues, suitable for both clinical and functional imaging use. Methods: We recruited 23 participants (14 with dementia, 6 of whom had extrapyramidal motor features, and 9 age-matched controls). The novel Newcastle visual perception prototype battery (NEVIP-B-Prototype) included angle, color, face, motion and form perception tasks, and an adapted response system. It allows for individualized task difficulties. Participants were tested outside and inside the 3T functional magnetic resonance imaging (fMRI) scanner. Functional magnetic resonance imaging data were analyzed using SPM8. Results: All participants successfully completed the task inside and outside the scanner. Functional magnetic resonance imaging analysis showed activation regions corresponding well to the regional specializations of the visual association cortex. In both groups, there was significant activity in the ventral occipital-temporal region in the face and color tasks, whereas the motion task activated the V5 region. In the control group, the angle task activated the occipitoparietal cortex. Patients and controls showed similar levels of activation, except on the angle task for which occipitoparietal activation was lower in patients than controls. Conclusion: Distinct visuoperceptual functions can be tested in patients with dementia and extrapyramidal motor features when tests use individualized thresholds, adapted tasks, and specialized response systems.

Predicting asthma control and exacerbations: chronic asthma as a complex dynamic model

PURPOSE OF REVIEW: Predicting asthma episodes is notoriously difficult but has potentially significant consequences for the individual, as well as for healthcare services. The purpose of this review is to describe recent insights into the prediction of acute asthma episodes in relation to classical clinical, functional or inflammatory variables, as well as present a new concept for evaluating asthma as a dynamically regulated homeokinetic system. RECENT FINDINGS: Risk prediction for asthma episodes or relapse has been attempted using clinical scoring systems, considerations of environmental factors and lung function, as well as inflammatory and immunological markers in induced sputum or exhaled air, and these are summarized here. We have recently proposed that newer mathematical methods derived from statistical physics may be used to understand the complexity of asthma as a homeokinetic, dynamic system consisting of a network comprising multiple components, and also to assess the risk for future asthma episodes based on fluctuation analysis of long time series of lung function. SUMMARY: Apart from the classical analysis of risk factor and functional parameters, this new approach may be used to assess asthma control and treatment effects in the individual as well as in future research trials.

FUNCTIONAL PRINCIPAL COMPONENTS MODEL FOR HIGH-DIMENSIONAL BRAIN IMAGING

We establish a fundamental equivalence between singular value decomposition (SVD) and functional principal components analysis (FPCA) models. The constructive relationship allows to deploy the numerical efficiency of SVD to fully estimate the components of FPCA, even for extremely high-dimensional functional objects, such as brain images. As an example, a functional mixed effect model is fitted to high-resolution morphometric (RAVENS) images. The main directions of morphometric variation in brain volumes are identified and discussed.

Health risk appraisal in older people 3: prevalence, impact, and context of pain and their implications for GPs

BACKGROUND: Pain is a common experience in later life. There is conflicting evidence of the prevalence, impact, and context of pain in older people. GPs are criticised for underestimating and under-treating pain. AIM: To assess the extent to which older people experience pain, and to explore relationships between self-reported pain and functional ability and depression. DESIGN OF STUDY: Secondary analysis of baseline data from a randomised controlled trial of health risk appraisal. SETTING: A total of 1090 community-dwelling non-disabled people aged 65 years and over were included in the study from three group practices in suburban London. METHOD: Main outcome measures were pain in the last 4 weeks and the impact of pain, measured using the 24-item Geriatric Pain Measure; depression symptoms captured using the 5-item Mental Health Inventory; social relationships measured using the 6-item Lubben Social Network Scale; Basic and Instrumental Activities of Daily Living and self-reported symptoms. RESULTS: Forty-five per cent of women and 34% of men reported pain in the previous 4 weeks. Pain experience appeared to be less in the 'oldest old': 27.5% of those aged 85 years and over reported pain compared with 38-53% of the 'younger old'. Those with arthritis were four times more likely to report pain. Pain had a profound impact on activities of daily living, but most of those reporting pain described their health as good or excellent. Although there was a significant association between the experience of pain and depressed mood, the majority of those reporting pain did not have depressed mood. CONCLUSION: A multidimensional approach to assessing pain is appropriate. Primary care practitioners should also assess the impact of pain on activities of daily living.

The neurophysiological time pattern of illusionary visual perceptual transitions: a simultaneous EEG and fMRI study

Several divergent cortical mechanisms generating multistability in visual perception have been suggested. Here, we investigated the neurophysiologic time pattern of multistable perceptual changes by means of a simultaneous recording with electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Volunteers responded to the subjective perception of a sudden change between stable patterns of illusionary motion (multistable transition) during a stroboscopic paradigm. We found a global deceleration of the EEG frequency prior to a transition and an occipital-accentuated acceleration after a transition, as obtained by low-resolution electromagnetic tomography analysis (LORETA) analysis. A decrease in BOLD response was found in the prefrontal cortex before, and an increase after the transitions was observed in the right anterior insula, the MT/V5 regions and the SMA. The thalamus and left superior temporal gyrus showed a pattern of decrease before and increase after transitions. No such temporal course was found in the control condition. The multimodal approach of data acquisition allows us to argue that the top-down control of illusionary visual perception depends on selective attention, and that a diminution of vigilance reduces selective attention. These are necessary conditions to allow for the occurrence of a perception discontinuity in absence of a physical change of the stimulus.

Influence of preoperative functional status on outcome after total hip arthroplasty

BACKGROUND: International registries with large, heterogeneous patient populations provide excellent research opportunities for studying factors that influence treatment outcomes after total hip arthroplasty. In the present study, we used a European multinational database to investigate whether there is an association between three functional variables (preoperative pain, mobility, and motion) and functional outcome. METHODS: We performed a retrospective cohort study on preoperative and follow-up clinical data that were prospectively entered into the International Documentation and Evaluation System European hip registry between 1967 and 2002. The inclusion criteria for this study were an age of more than twenty years, an underlying diagnosis of osteoarthritis, and a Charnley class-A functional designation at the time of surgery. A total of 12,925 patients (13,766 total hip arthroplasties) who met these criteria were entered into the analysis. Three functional variables (pain, mobility, and motion) that were assessed preoperatively were evaluated postoperatively at various follow-up examinations for a maximum of ten years. RESULTS: Six thousand four hundred and one patients could walk longer than ten minutes preoperatively; of these, 57.1% had a walking capacity of more than sixty minutes at the time of the most recent follow-up. In comparison, 6896 patients had a preoperative walking capacity of less than ten minutes and only 38.9% of these patients could walk more than sixty minutes at the time of the most recent follow-up. The difference was significant (p < 0.01). Similarly, 10,375 patients had a preoperative hip flexion range of >70 degrees ; of these, 74.7% had a flexion range of >90 degrees at the time of the most recent follow-up. In comparison, 2793 patients had a preoperative hip flexion range of <70 degrees and only 62.6% of these patients had a flexion range of >90 degrees at the time of the most recent follow-up. The difference was also significant (p < 0.01). Lasting, complete, or almost complete pain relief was achieved by >80% of the patients following total hip arthroplasty regardless of their preoperative categorization of pain. CONCLUSIONS: Patients with poor preoperative walking capacity and hip flexion are less likely to achieve an optimal outcome with regard to walking and motion. In contrast, there is no correlation between the preoperative pain level and pain alleviation, which is generally good and long-lasting after total hip arthroplasty.

Depression, the metabolic syndrome and cardiovascular risk

BACKGROUND: The relationship between depression and the metabolic syndrome is unclear, and whether metabolic syndrome explains the association between depression and cardiovascular disease (CVD) risk is unknown. METHODS: We studied 652 women who received coronary angiography as part of the Women's Ischemia Syndrome Evaluation (WISE) study and completed the Beck Depression Inventory (BDI). Women who had both elevated depressive symptoms (BDI > or =10) and a previous diagnosis of depression were considered at highest risk, whereas those with one of the two conditions represented an intermediate group. The metabolic syndrome was defined according to the ATP-III criteria. The main outcome was incidence of adverse CVD events (hospitalizations for myocardial infarction, stroke, congestive heart failure, and CVD-related mortality) over a median follow-up of 5.9 years. RESULTS: After adjusting for demographic factors, lifestyle and functional status, both depression categories were associated with about 60% increased odds for metabolic syndrome compared with no depression (p = .03). The number of metabolic syndrome risk factors increased gradually across the three depression categories (p = .003). During follow-up, 104 women (15.9%) experienced CVD events. In multivariable analysis, women with both elevated symptoms and a previous diagnosis of depression had 2.6 times higher risk of CVD. When metabolic syndrome was added to the model, the risk associated with depression only decreased by 7%, and both depression and metabolic syndrome remained significant predictors of CVD. CONCLUSIONS: In women with suspected coronary artery disease, the metabolic syndrome is independently associated with depression but explains only a small portion of the association between depression and incident CVD.

Within-subject comparison of two rigid bar designs connecting two interforaminal implants: patients' satisfaction and prosthetic results

BACKGROUND: There is evidence for the superiority of two-implant overdentures over complete dentures in the mandible. Various anchorage devices were used to provide stability to overdentures. The aim of the present study was to compare two designs of a rigid bar connecting two mandibular implants. MATERIALS AND METHODS: Completely edentulous patients received a new denture in the maxilla and an implant-supported overdenture in the mandible. They were randomly allocated to two groups (A or B) with regard to the bar design. A standard U-shaped bar (Dolder bar) was used connecting the two implants in a straight line. For comparison, precision attachments were soldered distal to the bar copings. Group A started the study with the standard bar (S-bar), while group B started with the attachment-bar (A-bar). After 3 months, they had to answer a questionnaire (visual analogue scale [VAS]); then the bar design was changed in both groups. After a period of another 3 months, the patients had to answer the same questions; then they had the choice to keep their preferred bar. Now the study period was extended to another year of observation, and the patients answered again the same questionnaire. In vivo force measurements were carried out with both bar types at the end of the test periods. The prosthetic maintenance service carried out during the 6-month period was recorded for both bar types in both groups. Statistical analysis as performed with the SPSS statistical package (SPSS Inc., Chicago, IL, USA). RESULTS: Satisfaction was high in both groups. Group B, who had entered the study with the attachment bar, gave slightly better ratings to this type for four items, while in group A, no differences were found. At the end of the 6-month comparison period, all but one patient wished to continue to wear the attachment bar. Prosthetic service was equal in groups A and B, but the total number of interventions is significantly higher in the attachment bar. Force patterns of maximum biting were similar in both bar designs, but exhibited significantly higher axial forces in the attachment bar. CONCLUSIONS: Both bar designs provide good retention and functional comfort. High stability appears to be an important factor for the patients' satisfaction and oral comfort. Rigid retention results in a higher force impact and appears to evoke the need for the retightening of occlusal screws, resulting in more maintenance service.

The relationship between pain intensity and severity and depression in older people: exploratory study

BACKGROUND: Pain and depression are known to be associated in later life, and both have a negative effect on physical performance both separately and in combination. The nature of the relationships between pain intensity and depression in elderly persons experiencing pain is less clear. The objectives of this study were to explore which factors are associated with depressed mood in older people experiencing pain, and to test the hypothesis that older people experiencing pain are at risk of depressed mood according to the severity or frequency of their pain. In addition we explored whether other potentially modifiable factors might increase the risk of depressed mood in these persons. METHODS: The study is a secondary analysis of baseline data for four hundred and six community-dwelling non-disabled people aged 65 and over registered with three group practices in suburban London who had experienced pain in the past 4 weeks. Intensity and frequency of pain was measured using 24 item Geriatric Pain Measure (GPM) and the presence of depressive symptoms using the 5 item Mental Health Inventory. Risk for social isolation was measured using the 6 item Lubben Social Network scale and instrumental activities of daily living (IADL) were also measured. RESULTS: Overall 76 (19%) had depressed mood. Pain frequency and severity were not statistically significantly associated with depressed mood in this population. In multivariate analyses, significant predictors of the presence of depressive symptoms were difficulties with basic ADLs (OR 2.8, 95% CI 1.1.7.8), risk for social isolation (OR 4.1, 95% CI 1.8-9.3), and basic education only (OR 2.2, 95% CI 1.1-4.4). CONCLUSION: Older people experiencing pain are also likely to experience depression. Among those experiencing pain, social network and functional status seem to be more important predictors of depressive symptoms than the severity of pain. Further studies should evaluate whether improvement of social network and functional status might reduce depressive symptoms in older patients.