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Introduction: This systematic review aims to provide an overview of predictors for failure of treatment of displaced femoral neck fracture (dFNF) with internal fixation and quantify their risk of fixation failure in a meta-analysis.Patients and Methods: PubMed, Embase, Web of Science, Cochrane Library, and EMCare were searched for original studies published from January 2000, including adult patients with an internally fixated dFNF, that reported data on predictors for fixation failure defined as revision surgery due to non-union, avascular femoral head necrosis or cut-out of implant. RevMan version 5 software was used to pool univariable Odds Ratio's (OR) for predictors of fixation failure by means of a random effects model.Results: This review included 16 articles (15 articles cohort studies and one randomised trial). Twenty-four predictors for fixation failure were identified and analysed, 16 of which were evaluated in just one study. Data of 7 predictors were pooled in a meta-analysis. Female sex (OR 1.78, 95% confidence interval [CI] 1.26-2.52), smoking (OR 3.64, 95% CI 1.68-7.91), age >50 years (OR 3.64, 95% CI 1.68-7.91), inadequate fracture reduction (OR 2.28, 95% CI 1.62-3.22), fixation with cannulated screws (CS) or pins compared to fixed angle devices (OR 2.16, 95% CI 1.03-4.54) were identified as significant predictors for fixation failure.Conclusion: This study can help surgeons to choose the preferred treatment for patients with a dFNF and substantiate future algorithms and guidelines for treatment of FNF. [ABSTRACT FROM AUTHOR]

Objective: Osteoarthritis (OA) is a chronic joint disease characterized by progressive degradation of cartilage. It affects more than 10% of the people aged over 60 years-old worldwide with a rising prevalence due to the increasingly aging population. OA is a major source of pain, disability, and socioeconomic cost. Currently, the lack of effective diagnosis and affordable imaging options for early detection and monitoring of OA presents the clinic with many challenges. Spectroscopic Photoacoustic (sPA) imaging has the potential to reveal changes in cartilage composition with different degrees of damage, based on optical absorption contrast.Design: In this study, the capabilities of sPA imaging and its potential to characterize cartilage damage were explored. To this end, 15 pieces of cartilage samples from patients undergoing a total joint replacement were collected and were imaged ex vivo with sPA imaging at a wide optical spectral range (between 500 nm and 1,300 nm) to investigate the photoacoustic properties of cartilage tissue. All the PA spectra of the cartilage samples were analyzed and compared to the corresponding histological results.Results: The collagen related PA spectral changes were clearly visible in our imaging data and were related to different degrees of cartilage damage. The results are in good agreement with histology and the current gold standard, i.e., the Mankin score.Conclusions: This study demonstrates the potential and possible clinical application of sPA imaging in OA. [ABSTRACT FROM AUTHOR]

Objective: The clinical success of focal metallic resurfacing implants depends largely on the friction between implant and opposing cartilage. Therefore, the present study determines the lubricating ability of the synovial fluid components hyaluronic acid (HA), proteoglycan 4 (PRG4) and a surface-active phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC), on the articulation between cartilage and a Cobalt Chromium Molybdenum (CoCrMo) implant surface, compared with two cartilage surfaces.Methods: A ring-on-disk geometry was used to perform repeated friction measurements at physiologically relevant velocities (6 and 60 mm/s) using lubricants with an increasing number of components present. Shear measurements were performed in order to evaluate the viscosity. To ensure that it is clinically relevant to explore the effect of these components, the presence of PRG4 in synovial fluid obtained from primary and revision knee and hip implant surgeries was examined.Results: PRG4 in the presence of HA was found to significantly reduce the coefficient of friction for both cartilage-cartilage and cartilage-CoCrMo interface. This is relevant, as it was also demonstrated that PRG4 is still present at the time of revision surgeries. The addition of POPC had no effect for either configurations. HA increased the viscosity of the lubricating fluid by one order of magnitude, while PRG4 and POPC had no effect.Conclusion: The present study demonstrates the importance of selecting the appropriate lubrication solution to evaluate implant materials with biotribology tests. Because PRG4 is a key component for reducing friction between cartilage and an opposing surface, developing coatings which bind PRG4 is recommended for cartilage resurfacing implants. [ABSTRACT FROM AUTHOR]

• Pyoderma Gangrenosum (PG) is a rare auto-inflammatory disease. • It can develop after surgery due to the pathergy phenomena. • Consider PG in the differential diagnosis of a suspected surgical wound infection. • Avoid surgical treatment as long as the disease is active to reduce morbidity. Pyoderma Gangrenosum (PG) is a rare auto-inflammatory disease, characterized by painful ulcerative skin-lesions often developing at sites of injury or surgery because of the typical pathergy phenomena. We describe an unusual case of PG after a caesarean section with excessive extra-cutaneous manifestation within internal organs. A 21-year-old Dutch primigravida developed signs of sepsis after a caesarean section. Despite antibiotic treatment, fast clinical deterioration occurred. Exploration of the wound showed necrosis of the uterus and surrounding tissues. Due to the progression of necrosis, consecutive debridement procedures were executed resulting in a substantial abdominal wall defect. The progressive clinical course of the necrosis combined with absence of positive wound cultures and histology of prominent interstitial neutrophilic infiltration, led to the diagnosis 'Pyoderma Gangrenosum'. Treatment with high dose corticosteroids led to rapid regression of the disease. After several weeks, the abdominal wall defect was surgically corrected under systemic corticosteroid therapy. This case of PG is unique due to the excessive extra-cutaneous presentation, which contributed to delayed diagnosis. Several surgical interventions in the active stage of disease resulted in expansion of PG and substantial morbidity for the patient. Post-operative PG can mimic infectious diseases, but treatment is substantially different. This case of extensive PG highlights the importance of timely recognition and treatment of the disease to reduce iatrogenic morbidity. [ABSTRACT FROM AUTHOR]

Exposure to fine particulate matter (PM 2.5) is the leading environmental risk factor for mortality globally. Satellite-derived estimates of surface PM 2.5 developed from a combination of satellites, simulations, and ground monitor data are relied upon for health impact studies. The ability to develop satellite-derived PM 2.5 estimates requires the continued availability of aerosol optical depth (AOD) sources. This work examines the impact of the addition or loss of satellite AOD data sources on global PM 2.5 estimation and the impact of continuing the long-term record with AOD from the Visible Infrared Imaging Radiometer Suite (VIIRS) on the Suomi-National Polar orbiting Partnership (S-NPP) satellite after the loss of the MODIS (MODerate resolution Imaging Spectroradiometer) and MISR (Multi-angle Imaging Spectroradiometer) instruments on board the Terra and Aqua satellites. We find that the addition of VIIRS S-NPP AOD products to geophysical PM 2.5 estimates from satellites and simulations causes regional differences that correspond to differences in the VIIRS and MODIS Deep Blue AOD algorithms and sampling. Changes in long-term trends and timeseries due to the addition or loss of AOD data sources are generally within their uncertainties. Statistical fusion with ground monitor data partially corrects for changes due to sampling differences when introducing the VIIRS AOD products, but uncertainty remains over desert regions where ground monitor coverage is sparse. This work provides promise for the sustained development of global satellite-derived PM 2.5 estimates, despite discontinuities in instruments and retrieval methods. • Impact of changing satellite AOD sources on global PM 2.5 estimation is examined. • Algorithm inconsistencies and sampling cause regional differences in PM 2.5. • Changes in trends due to the discontinuity of AOD sources are within uncertainties. • Statistical fusion with ground monitors partially corrects for sampling impacts. • Global sat-derived PM 2.5 record is sustained despite AOD source discontinuities. [ABSTRACT FROM AUTHOR]

Exposure to ambient air pollution may affect cognitive functioning and development in children. Unfortunately, there is little evidence available for low- and middle-income countries (LMICs), where air pollution levels are highest. We analysed the association between exposure to ambient fine particulate matter (≤2.5 μm [PM 2.5 ]) and cognitive development indicators in a cross-sectional analysis of children (aged 3–4 years) in 12 LMICs. We linked Demographic and Health Survey data, conducted between 2011 and 2018, with global estimates of PM 2.5 mass concentrations to examine annual average exposure to PM 2.5 and cognitive development (literacy-numeracy and learning domains) in children. Cognitive development was assessed using the United Nations Children's Fund's early child development indicators administered to each child's mother. We used multivariable logistic regression models, adjusted for individual- and area-level covariates, and multi-pollutant models (including nitrogen dioxide and surface-level ozone). We assessed if sex and urban/rural status modified the association of PM 2.5 with the outcome. We included 57,647 children, of whom, 9613 (13.3%) had indicators of cognitive delay. In the adjusted model, a 5 μg/m3 increase in annual all composition PM 2.5 was associated with greater odds of cognitive delay (OR = 1.17; 95% CI: 1.13, 1.22). A 5 μg/m3 increase in anthropogenic PM 2.5 was also associated with greater odds of cognitive delay (OR = 1.05; 95% CI: 1.00, 1.10). These results were robust to several sensitivity analyses, including multi-pollutant models. Interaction terms showed that urban-dwelling children had greater odds of cognitive delay than rural-dwelling children, while there was no significant difference by sex. Our findings suggest that annual average exposure to PM 2.5 in young children was associated with adverse effects on cognitive development, which may have long-term consequences for educational attainment and health. [Display omitted] • The effects of ambient PM 2.5 on early cognitive development are scarcely studied. • We examined the association of PM 2.5 and cognitive delay in low-income countries. • Ambient PM 2.5 exposure is associated with significant cognitive delay in children. • The odds of cognitive delay associated with PM 2.5 was greater in urban children. [ABSTRACT FROM AUTHOR]

Studies examining long-term effects of ambient air pollution exposure, measured as annual averages, on pulmonary tuberculosis (TB) incidence are scarce, particularly in endemic, rural settings. We performed a small-area study in Ningxia Hui Autonomous Region (NHAR), a high TB-burden area in rural China, using township-level (n = 358 non-overlapping townships) annual TB notification data (2005–2017). We aimed to determine if annual average concentrations of ambient air pollution (particulate matter <2·5 μm [PM 2·5 ], nitrogen dioxide [NO 2 ] ozone [O 3 ]) were associated with TB notification rates (as a proxy for incidence). Air pollution effects on TB notification rates at township-level were estimated as incidence rate ratios (IRR), fitted using a generalised estimating equation (GEE) adjusted for covariates (age, sex, occupation, education, ethnicity, remoteness [urban or rural], household crowding and solid fuel use). A total of 38,942 TB notifications were reported in NHAR between 2005 and 2017. The mean annual TB notification rate was 67 (standard deviation [SD]; 7) per 100,000 people. Median concentrations of PM 2·5 , NO 2 , and O 3 were 42 μg/m3 (interquartile range [IQR]; 38–48 μg/m3), 15 ppb (IQR; 12–16 ppb), and 56 ppb (IQR; 56–57 ppb), respectively. In single pollutant models, adjusted for covariates, an interquartile range (IQR) increase (10 μg/m3) in PM 2·5 was significantly associated with higher TB notification rates (IRR: 1∙35; 95% CI: 1·25–1·48). Comparable effects on notifications of TB were observed for increases in NO 2 exposure (IRR: 1·20 per IQR (4 ppb) increase; 95% CI: 1·08–1·31). Ground-level ozone was not associated with TB notification rate in any models. The observed effects were consistent over time, in multi-pollutant models, and appeared robust to additional adjustment for indicators of household crowding, solid fuel use and remoteness. More rigorous study designs are needed to understand if improving air quality has population-level benefits on TB disease incidence in endemic settings. [Display omitted] • Annual average PM 2.5 and NO 2 exposure contributed to higher TB notifications rates. • Ground-level ozone exposure was not associated with TB notification rates. • Improvements in air quality could help alleviate the burden of TB. [ABSTRACT FROM AUTHOR]

Cartilage defects occur frequently and can lead to osteoarthritis. Hydrogels are a promising regenerative strategy for treating such defects, using their ability of mimicking the native extracellular matrix. However, commonly used hydrogels for tissue regeneration are too soft to resist load-bearing in the joint. To overcome this, an implant is being developed in which the mechanical loadbearing function originates from the osmotic pressure generated by the swelling potential of a charged hydrogel, which is restricted from swelling by a textile spacer fabric. This study aims to quantify the relationship between the swelling potential of the hydrogel and the compressive stiffness of the implant. [ABSTRACT FROM AUTHOR]

The exergetic performance of beer produced by the conventional malting and brewing process is compared with that of beer produced using an enzyme-assisted process. The aim is to estimate if the use of an exogenous enzyme formulation reduces the environmental impact of the overall brewing process. The exergy efficiency of malting was 77%. The main exergy losses stem from the use of natural gas for kilning and from starch loss during germination. The exergy efficiency of the enzyme production process ranges between 20% and 42% depending on if the by-product was considered useful. The main exergy loss was due to high power requirement for fermentation. The total exergy input in the enzyme production process was 30 times the standard chemical exergy of the enzyme, which makes it exergetically expensive. Nevertheless, the total exergy input for the production of 100 kg beer was larger for the conventional process (441 MJ) than for the enzyme-assisted process (354 MJ). Moreover, beer produced using enzymes reduced the use of water, raw materials and natural gas by 7%, 14% and 78% respectively. Consequently, the exergy loss in the enzyme production process is compensated by the prevention of exergy loss in the total beer brewing process. [ABSTRACT FROM AUTHOR]

When studying the glass-to-rubber transition inside natural materials, it is important to take into account not only the moisture content but also the moisture distribution over the components in the material. We measured the T g of protein and starch isolated from barley at different moisture contents using differential scanning calorimetry (DSC) (heating rate 10 °C/min) and by thermo mechanical compression tests (TMCT) (heating rate 2 °C/min). The measurement of the T g of partially crystalline materials, such as barley starch, is more difficult using TMCT because the mechanical effect of expansion of these materials is smaller. For both measurement sets the glass transition lines were modeled using the Gordon–Taylor equation. The lines were adapted for the differences in moisture content over the endosperm by using the sorption isotherms of isolated barley starch and protein and whole barley endosperm. The glass transition lines measured by TMCT were closer together than the ones measured by DSC. [ABSTRACT FROM AUTHOR]

Partly replacing malt with unmalted barley is a trend in brewing. The use of unmalted barley, however, leads to issues such as haze and high mash viscosity, due to its higher content of undesired components. Pearling, an abrasive method to remove the outer layers of the barley kernels has been shown to reduce the content of insoluble fibre, ash, protein and polyphenols; the β-amylase activity and starch content of the remaining kernel were hardly affected. Removing the outer 5% of the kernel, for example, results in a 15% reduction of insoluble arabinoxylans, 23% of the insoluble fibre content and 25% of the water holding capacity of the non-starch components. It also reduces the ash content by 19% and the polyphenol content by 11%, but only 0.20% of the starch is pearled off. A relation was found between the insoluble fibre content and the water holding capacity of a fraction. Lower fibre content reduces the water holding capacity and thus the volume of the spent grains, which implies that less wort and sugar are lost during filtration. In addition, that the bran fraction remains dry, implies a reduction in energy required to dry the spent grains. [ABSTRACT FROM AUTHOR]

Horizontal visibility measured at ground meteorological stations provides an under-exploited source of information for studying the interdecadal variation of aerosols and their climatic impacts. Here we propose to use a 3-hourly visibility dataset to infer aerosol optical depth (AOD) over East China, using the nested GEOS-Chem chemical transport model to interpret the spatiotemporally varying relations between columnar and near-surface aerosols. Our analysis is focused in 2006 under cloud-free conditions. We evaluate the visibility-inferred AOD using MODIS/Terra and MODIS/Aqua AOD datasets, after validating MODIS data against three ground AOD measurement networks (AERONET, CARSNET and CSHNET). We find that the two MODIS datasets agree with ground-based AOD measurements, with negative mean biases of 0.05-0.08 and Reduced Major Axis regression slopes around unity. Visibility-inferred AOD roughly capture the general spatiotemporal patterns of the two MODIS datasets with negligible mean differences. The inferred AOD reproduce the seasonal variability (correlation exceeds 0.9) and the slight AOD growth from the late morning to early afternoon shown in the MODIS datasets, suggesting the validity of our AOD inference method. Future research will extend the visibility-based AOD inference to study the long-term variability of AOD. [ABSTRACT FROM AUTHOR]

Summary: Objective: Proteoglycan (PG) loss and surface roughening, early signs of osteoarthritis (OA), are likely preceded by softening of the ground substance and the collagen network. Insight in their relative importance to progression of OA may assist the development of treatment strategies for early OA. To support interpretation of experimental data, a numerical model is proposed that can predict damage progression in cartilage over time, as a consequence of excessive mechanical loading. The objective is to assess the interaction between ground substance softening and collagen fiber damage using this model. Design: An established cartilage mechanics model is extended with the assumption that excessive strains may damage the ground substance or the collagen network, resulting in softening of the overstrained constituent. During subsequent loading cycles the strain may or may not cross a threshold, resulting in damage to stabilize or to progress. To evaluate how softening of the ground substance and collagen may interact, damage progression is computed when either one of them, or both together are allowed to occur during stepwise increased loading. Results: Softening in the ground substance was predicted to localize in the superficial and transitional zone and resulted in cartilage softening. Collagen damage was most prominent in the superficial zone, with more diffuse damage penetrating deeper into the tissue, resulting in adverse strain gradients. Effects were more pronounced if both constituents developed damage in parallel. Conclusion: Ground substance softening and collagen damage have distinct effects on cartilage mechanopathology, and damage in either one of them may promote each other. [Copyright &y& Elsevier]

Summary: Objective: Osteoarthritis (OA) is characterized by loss of cartilage and alterations in subchondral bone architecture. Changes in cartilage and bone tissue occur simultaneously and are spatially correlated, indicating that they are probably related. We investigated two hypotheses regarding this relationship. According to the first hypothesis, both wear and tear changes in cartilage, and remodeling changes in bone are a result of abnormal loading conditions. According to the second hypothesis, loss of cartilage and changes in bone architecture result from endochondral ossification. Design: With an established bone adaptation model, we simulated adaptation to high load and endochondral ossification, and investigated whether alterations in bone architecture between these conditions were different. In addition, we analyzed bone structure differences between human bone samples with increasing degrees of OA, and compared these data to the simulation results. Results: The simulation of endochondral ossification led to a more refined structure, with a higher number of trabeculae in agreement with the finding of a higher trabecular number in osteochondral plugs with severe OA. Furthermore, endochondral ossification could explain the presence of a “double subchondral plate” which we found in some human bone samples. However, endochondral ossification could not explain the increase in bone volume fraction that we observed, whereas adaptation to high loading could. Conclusion: Based on the simulation and experimental data, we postulate that both endochondral ossification and adaptation to high load may contribute to OA bone structural changes, while both wear and tear and the replacement of mineralized cartilage with bone tissue may contribute cartilage thinning. [ABSTRACT FROM AUTHOR]

Summary: Objective: Because collagen damage and cartilage softening have not yet been determined simultaneously in one study for the very early onset of osteoarthritis (OA), it remains questionable whether they are associated. The aim of the present study is therefore to evaluate whether indeed, initial collagen damage can be found when tissue softening occurs as a result of excessive mechanical loading. Methods: To investigate this aim, a series of specific indentation loading protocols were designed to induce and monitor cartilage softening in osteochondral explants of bovine carpometacarpal joints. The experiment contained one control group (n = 6) in which no damage was induced and four experimental groups in which samples received either a constant load of 3 (n = 5), 6 (n = 5) or 15 N (n = 6), or an increasing load (n = 7) from 2 to 13 N in 11 steps. Moreover, to determine mechanically induced collagen damage, Col2-3/4M (cumulative collagen damage) and Col2-3/4Cshort (only enzymatic damage) staining were compared. Results: The normalized peak and equilibrium reaction forces decreased in the groups that received increasing and 15 N peak loading. However, Col2-3/4M staining was negative in all samples, while enzymatic damage (Col2-3/4Cshort) appeared similar in experiments and in unloaded control groups. Conclusion: It was shown that a loading magnitude threshold exists above which softening occurs in cartilage. However, in samples that did show softening, we were unable to detect collagen damage. Thus, our results demonstrate that cartilage softening most likely precedes collagen damage. [Copyright &y& Elsevier]

Abstract: For many years, pharmaceutical therapies for osteoarthritis (OA) were focused on cartilage. However, it has been theorized that bone changes such as increased bone volume fraction and decreased bone matrix mineralization may play an important role in the initiation and pathogenesis of OA as well. The mechanisms behind the bone changes are subject of debate, and a better understanding may help in the development of bone-targeting OA therapies. In the literature, the increase in bone volume fraction has been hypothesized to result from mechanoregulated bone adaptation in response to decreased mineralization. Furthermore, both changes in bone volume fraction and mineralization have been reported to be highest close to the cartilage, and bone volume fraction has been reported to be correlated with cartilage degeneration. These data indicate that cartilage degeneration, bone volume fraction, and bone matrix mineralization may be related in OA. In the current study, we aimed to investigate the relationships between cartilage degeneration, bone matrix mineralization and bone volume fraction at a local level. With microCT, we determined bone matrix mineralization and bone volume fraction as a function of distance from the cartilage in osteochondral plugs from human OA tibia plateaus with varying degrees of cartilage degeneration. In addition, we evaluated whether mechanoregulated bone adaptation in response to decreased bone matrix mineralization may be responsible for the increase in bone volume fraction observed in OA. For this purpose, we used the experimentally obtained mineralization data as input for bone adaptation simulations. We simulated the effect of mechanoregulated bone adaptation in response to different degrees of mineralization, and compared the simulation results to the experimental data. We found that local changes in subchondral bone mineralization and bone volume fraction only occurred underneath severely degenerated cartilage, indicating that bone mineralization and volume fraction are related to cartilage degeneration at a local level. In addition, both the experimental data and the simulations indicated that a depth-dependent increase in bone volume fraction could be caused by decreased bone matrix mineralization. However, a quantitative comparison showed that decreased mineralization can only explain part of the subchondral sclerosis observed in OA. [Copyright &y& Elsevier]

Background: Serotonin (5-hydroxytryptamine; 5-HT), a tryptophan metabolite, plays an important regulatory role in the human central nervous system and in the gastrointestinal tract. Acute tryptophan depletion (ATD) is currently the most widely established method to investigate 5-HT metabolism. Objective: The aim of this study was to assess the effect of an acute decrease in the systemic availability of tryptophan on intestinal 5-HT metabolism and permeability. Design: Thirty-three healthy volunteers (17 with ATD, 3 of whom dropped out; 16 placebo), participated in this randomized placebo- controlled study. Plasma and duodenal mucosal concentrations of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and kynurenic acid (KA) were measured by HPLC-mass spectrometry. Intestinal barrier function was assessed with a multisugar plasma test, and analysis of tight junction transcription was performed in duodenal biopsy samples obtained by gastroduodenoscopy. Results: Mucosal 5-HT, 5-HIAA, and KA concentrations remained unaltered by ATD. In contrast, ATD significantly decreased plasma 5-HT (P < 0.05) and 5-HIAA (P < 0.0001) concentrations. After endoscopy, a significant increase in plasma 5-HT concentrations was observed in the placebo group (P = 0.029) compared with the ATD group. Moreover, a significant increase in plasma KA concentrations over time was found in the placebo group (P < 0.05). No changes in intestinal barrier function were observed. Conclusions: An acute decrease in precursor availability does not affect mucosal concentrations of serotonergic metabolites, in contrast with systemic concentrations. ATD alters biochemical responses to acute stress from the endoscopic examination reflected by lower 5-HT concentrations. Changes in 5-HT concentrations were paralleled by alterations in KA concentrations, which suggest competition between the 2 metabolic pathways for the mutual precursor. This trial was registered at clinicaltrials.gov as NCT00731003. [ABSTRACT FROM AUTHOR]

Abstract: We estimate fine particulate matter (PM2.5) concentrations daily using MODIS satellite observations of aerosol optical depth (AOD) for a major biomass burning event around Moscow during summer 2010. Evaluation of MODIS AOD with the Moscow AERONET site supports a MODIS-AOD error estimate of ±(0.05+0.2×AOD) for this event. However, since the smoke was often thick (AOD>4.0) and spatially variable, the standard MODIS algorithm incorrectly identifies some aerosol as cloud. We test relaxed cloud screening criteria that increase MODIS coverage by 21% and find excellent agreement with coincident operational retrievals (r 2 =0.994, slope=1.01) with no evidence of false aerosol detection. We relate the resultant MODIS AOD to PM2.5 using aerosol vertical profiles from the GEOS-Chem chemical transport model. Our estimates are in good agreement with PM2.5 values estimated from in-situ PM10 (r 2 =0.85, slope=1.06), and we find that the relationship between AOD and PM2.5 is insensitive to uncertainties in biomass burning emissions. The satellite-derived and in-situ values both indicate that peak daily mean concentrations of approximately 600μgm−3 occurred on August 7, 2010 in the Moscow region of the Russian Federation. We estimate that exposure to air pollution from the Moscow wildfires may have caused hundreds of excess deaths. [Copyright &y& Elsevier]

Summary: Objective: There are strong indications that subchondral bone may play an important role in osteoarthritis (OA), making it an interesting target for medical therapies. The subchondral bone structure changes markedly during OA, and it has long been assumed that this occurs secondary to cartilage degeneration. However, for various conditions that are associated with OA, it is known that they may also induce bone structural changes in the absence of cartilage degeneration. We therefore aimed to investigate if OA bone structural changes can result from mechanoregulated bone adaptation, independent of cartilage degeneration. Method: With a bone adaptation model, we simulated various conditions associated with OA –without altering the articular cartilage– and we evaluated if mechanoregulated bone remodeling by itself could lead to OA-like bone structural changes. Results: For each of the conditions, the predicted changes in bone structural parameters (bone fraction, trabecular thickness, trabecular number, and trabecular separation) were similar to those observed in OA. Conclusion: This indicates that bone adaptation in OA can be mechanoregulated with structural changes occurring independent of cartilage degeneration. [ABSTRACT FROM AUTHOR]

Abstract: The mechanism by which fibrous tissues adapt upon alterations in their mechanical environment remains unresolved. Here, we determine that periosteum in chick embryos resides in an identical mechanical state, irrespective of the developmental stage. This state is characterized by a residual tissue strain that corresponds to the strain in between the pliant and stiffer region of the force-strain curve. We demonstrate that periosteum is able to regain that mechanical equilibrium state in vitro, within three days upon perturbation of that equilibrium state. This adaptation process is not dependent on protein synthesis, because the addition of cycloheximide did not affect the response. However, a functional actin filament network is required, as is illustrated by a lack of adaptation in the presence of cytochalasin D. This led us to hypothesize that cells actively reduce collagen fiber crimp after tissue shortening, i.e. that in time the number of recruited fibers is increased via cell contraction. Support for this mechanism is found by visualization of fiber crimp with multiphoton microscopy before the perturbation and at different time points during the adaptive response. [ABSTRACT FROM AUTHOR]

Summary: Objective: In this study, we aim at tuning the differentiation of periosteum in an organ culture model towards cartilage, rich in collagen type II, using combinations of biochemical and mechanical stimuli. We hypothesize that addition of TGF-β will stimulate chondrogenesis, whereas sliding indentation will enhance collagen synthesis. Design: Periosteum was dissected from the tibiotarsus of 15-day-old chick embryos. Explants were embedded in between two agarose layers, and cultured without stimulation (control), with biochemical stimulation (10ng/ml TGF-β1), with mechanical stimulation (sliding indentation), or both biochemical and mechanical stimulations. Sliding indentation was introduced as a method to induce tensile tissue strain. Analysis included quantification of DNA, collagen and GAG content, conventional histology, and immunohistochemistry for collagen type I and II at 1 or 2 weeks of culture. Results: Embedding the periosteal explants in between agarose layers induced cartilage formation, confirmed by synthesis of sGAG and collagen type II. Addition of TGF-β1 to the culture medium did not further enhance this chondrogenic response. Applying sliding indentation only to the periosteum in between agarose layers enhanced the production of collagen type I, leading to the formation of fibrous tissue without any evidence of cartilage formation. However, when stimulated by both TGF-β1 and sliding indentation, collagen production was still enhanced, but now collagen type II, while sGAG was found to be similar to TGF-β1 or unloaded samples. Conclusions: The type of tissue produced by periosteal explants can be tuned by combining mechanical stimulation and soluble factors. TGF-β1 stimulated a chondrocyte phenotype and sliding indentation stimulated collagen synthesis. Such a combination may be valuable for improvement of the quality of tissue-engineered cartilage. [Copyright &y& Elsevier]

Abstract: Acute tryptophan depletion is extensively used to investigate the implication of serotonin in the onset of depressive disorders. In rats, it lowers peripheral tryptophan and decreases central serotonin concentrations. We aimed to establish the rat model of acute tryptophan depletion in the mouse for potential application as serotonin challenge tool in genetic mouse models of depression. Pharmacokinetic and behavioural effects of a tryptophan-free diet were examined in Swiss and C57BL/6 mice. Peripheral amino acids were measured and central tryptophan and serotonin concentrations were compared with anxiety and depression-like behaviour in the elevated zero-maze, forced swimming test or tail suspension test. While acute tryptophan depletion resulted in a 74% reduction of the plasma ratio tryptophan to the sum of other large neutral amino acids in Swiss mice 1h after administration (2×10ml/kg, 30min interval), there was only a 40% reduction in C57BL/6 mice. The latter did not show anxiety in the elevated zero-maze or increased immobility in the forced swimming test or tail suspension test. A higher dose (2×20ml/kg) with a longer interval (60min) reduced the ratio with 68% in C57BL/6 mice, lowered hippocampal serotonin turnover and had no functional effect when tested in the elevated zero-maze and forced swimming test. These findings have important implications for the use of acute tryptophan depletion in general and in particular for its application in mice. Although in healthy mice no clear central serotonin or functional effects were observed, further research is indicated using mice with pre-existing serotonin dysfunction, as they might be more vulnerable to acute tryptophan depletion. [Copyright &y& Elsevier]

Abstract: Acute tryptophan depletion (ATD) decreases the 5-HT precursor tryptophan (TRP) in blood and is used both clinically and preclinically to investigate the involvement of 5-HT in the development of depressive symptomatology. Depression is associated with both central 5-HT dysfunction and abnormalities in the normal relationship between regional cerebral blood flow (CBF) and glucose metabolism (CMRG). In this study, ATD was applied in Wistar rats to investigate the cerebrovascular effects of acute changes in peripheral TRP. Rats were orally fed with a protein–carbohydrate mixture, either containing or lacking TRP. Four hours later, CBF or CMRG was measured by quantitative autoradiographic imaging in 43 brain regions of interest (ROI). In plasma, ATD resulted in a 40% reduction in the ratio of TRP to the sum of other large neutral amino acids, but had no measurable effect upon TRP or 5-HT levels in hippocampus or prefrontal cortex. Nevertheless, ATD significantly reduced local CBF in 11 of the 43 brain ROIs, while local CMRG remained unchanged. Global analysis of all 43 ROIs revealed a close correlation between CBF and CMRG within both treatment groups. However, the overall ratio (=slope) after ATD (m=1.07) was significantly decreased compared to the control group (m=1.27), indicating a state of relative cerebral oligaemia. Since ATD induced a significant lowering of peripheral TRP, without affecting central TRP or 5-HT concentrations, the decrease in CBF and global change in the flow-metabolism relationship cannot be directly attributed to decreases in brain TRP availability. This could be explained if the raphe were selectively vulnerable to ATD, but the exact mechanism remains unknown. Nevertheless, these data suggest that cerebrovascular disturbances should be considered as a potential contributory factor in studies of serotonergic dysfunction, including depression, with important implications for imaging studies that use CBF alone as a measure of neuronal function. [Copyright &y& Elsevier]

Abstract: Computational models are employed as tools to investigate possible mechano-regulation pathways for tissue differentiation and bone healing. However, current models do not account for the uncertainty in input parameters, and often include assumptions about parameter values that are not yet established. The aim was to clarify the importance of the assumed tissue material properties in a computational model of tissue differentiation during bone healing. An established mechano-biological model was employed together with a statistical approach. The model included an adaptive 2D finite element model of a fractured long bone. Four outcome criteria were quantified: (1) ability to predict sequential healing events, (2) amount of bone formation at specific time points, (3) total time until healing, and (4) mechanical stability at specific time points. Statistical analysis based on fractional factorial designs first involved a screening experiment to identify the most significant tissue material properties. These seven properties were studied further with response surface methodology in a three-level Box–Behnken design. Generally, the sequential events were not significantly influenced by any properties, whereas rate-dependent outcome criteria and mechanical stability were significantly influenced by Young''s modulus and permeability. Poisson''s ratio and porosity had minor effects. The amount of bone formation at early, mid and late phases of healing, the time until complete healing and the mechanical stability were all mostly dependent on three material properties; permeability of granulation tissue, Young''s modulus of cartilage and permeability of immature bone. The consistency between effects of the most influential parameters was high. To increase accuracy and predictive capacity of computational models of bone healing, the most influential tissue mechanical properties should be accurately quantified. [Copyright &y& Elsevier]

Abstract: Silsupadol P, Shumway-Cook A, Lugade V, van Donkelaar P, Chou LS, Mayr U, Woollacott MH. Effects of single-task versus dual-task training on balance performance in older adults: a double-blind, randomized controlled trial. Objective: To compare the effect of 3 different approaches to balance training on dual-task balance performance in older adults with balance impairment. Design: A double-blind, randomized controlled trial. Setting: University research laboratory. Participants: Older adults (N=23) with balance impairment (mean age, 74.8y). They scored 52 or less on the Berg Balance Scale (BBS) and/or walked with a self-selected gait speed of 1.1m/s or less. Interventions: Participants were randomly assigned to 1 of 3 interventions: single-task training, dual-task training with fixed-priority instructions, and dual-task training with variable-priority instructions. Participants received 45-minute individualized training sessions, 3 times a week for 4 weeks. Main Outcome Measures: Gait speed under single-task and dual-task conditions was obtained at baseline, the second week, the end of training, and the twelfth week after the end of training. Other measures, including the BBS and the Activities-specific Balance Confidence (ABC) Scale, were collected at baseline and after training. Results: Participants in all groups improved on the BBS (P<.001; effect size [ES]=.72), and walked significantly faster after training (P=.02; ES=.27). When a cognitive task was added, however, only participants who received dual-task training with fixed-priority instructions and dual-task training with variable-priority instructions exhibited significant improvements in gait speed (P<.001, ES=.57; and P<.001, ES=.46, respectively). In addition, only the dual-task training with variable-priority instructions group demonstrated a dual-task training effect at the second week of training and maintained the training effect at the 12-week follow-up. Only the single-task training group showed a significant increase on the ABC after training (P<.001; ES=.61). Conclusions: Dual-task training is effective in improving gait speed under dual-task conditions in elderly participants with balance impairment. Training balance under single-task conditions may not generalize to balance control during dual-task contexts. Explicit instruction regarding attentional focus is an important factor contributing to the rate of learning and the retention of the dual-task training effect. [Copyright &y& Elsevier]

Abstract: Periosteal incision is one of the less severe interventions used to correct mild long bone growth pathologies. The mechanism responsible for this growth modulation is still unclear. A generally adopted hypothesis is that incision releases compressive force created by tensioned periosteum. We set out to evaluate the feasibility of this hypothesis by quantifying the stress level imposed on cartilage by periosteum tension in the rapid growth phase of chick embryos and evaluating if tension release could be responsible for modulating growth. Residual force in embryonic periosteum was measured in a tensile tester. A finite element model was developed, based on geometry determined using optical projection tomography in combination with histology. This model was then used to calculate the stress-distribution throughout the cartilage imposed by the periosteum force and to evaluate its possible contribution in modulating growth. Residual periosteal force in e17 chick tibiotarsi resulted in compressive stresses of 6kPa in the proliferative zone and tensile stresses up to 9kPa in the epiphyseal cartilage. Based on the literature, these compressive stresses are estimated to reduce growth rates by 1.1% and calculated tensile stresses increase growth rates by 1.7%. However, growth rate modulations between 8% and 28% are reported in the literature upon periosteum release. We therefore conclude that the increased growth, initiated by periosteal incision, is unlikely to be predominantly the result of mechanical release of cartilage compression by periosteum tension. However, increased epiphyseal growth rates due to periosteal tension, may contribute to bone morphogenesis by widening the epiphysis. [Copyright &y& Elsevier]

Abstract: Reilly DS, Woollacott MH, van Donkelaar P, Saavedra S. The interaction between executive attention and postural control in dual-task conditions: children with cerebral palsy. Objective: To investigate the interference between a secondary task and a postural task in children with cerebral palsy (CP). Design: In this exploratory study, a dual-task paradigm was used in which children stood in either a wide or a narrow stance position while simultaneously performing a visual working memory task calibrated to be of equitable attentional demand between groups. Setting: Study data were gathered in a university motor control laboratory. Participants: Children with CP (n=8; age range, 10−14y) were compared with typically developing older children (n=6; age range, 7−12y), and typically developing young children (n=5; age range, 4−6y). Interventions: Not applicable. Main Outcome Measures: Proficiency in postural control was measured by the range and root mean square of the velocity of center of pressure displacement in the mediolateral and anteroposterior directions, calculated from forceplate data. Accuracy of response was used as a measure of cognitive task performance. Capacity of the executive attention system was determined by assessing visual working memory capacity. Results: Children with CP, like the typically developing young children, were more unstable and had less executive attention capacity compared with older children, and like the typically developing young children, experienced dual-task interference in postural control in both stance positions. Children with ataxic CP also experienced decreased cognitive task performance in narrow stance. Conclusions: In designing therapeutic interventions for children with CP, it would be beneficial for clinicians to assess postural control in both single- and dual-task environments. [Copyright &y& Elsevier]

We investigate how a recently suggested pathway for production of secondary organic aerosol (SOA) affects the consistency of simulated organic aerosol (OA) mass in a global three-dimensional model of oxidant-aerosol chemistry (GEOS-Chem) versus surface measurements from the interagency monitoring of protected visual environments (IMPROVE) network. Simulations in which isoprene oxidation products contribute to SOA formation, with a yield of 2. 0% by mass reduce a model bias versus measured OA surface mass concentrations. The resultant increase in simulated OA mass concentrations during summer of 0. 6–1. 0μgm−3 in the southeastern United States reduces the regional RMSE to 0. 88μgm−3 from 1. 26μgm−3. Spring and fall biases are also reduced, with little change in winter when isoprene emissions are negligible. [Copyright &y& Elsevier]

Abstract: Endochondral ossification is the process of differentiation of cartilaginous into osseous tissue. Parathyroid hormone related protein (PTHrP), Indian hedgehog (Ihh) and vascular endothelial growth factor (VEGF), which are synthesized in different zones of the growth plate, were found to have crucial roles in regulating endochondral ossification. The aim of this study was to evaluate whether the three growth factors PTHrP, Ihh and VEGF, together, could regulate longitudinal growth in a normal human, fetal femur. For this purpose, a one-dimensional finite element (FE) model, incorporating growth factor signaling, was developed of the human, distal, femoral growth plate. It included growth factor synthesis in the relevant zones, their transport and degradation and their effects. Simulations ran from initial hypertrophy in the center of the bone until secondary ossification starts at approximately 3.5 months postnatal. For clarity, we emphasize that no mechanical stresses were considered. The FE model showed a stable growth plate in which the bone growth rate was constant and the number of cells per zone oscillated around an equilibrium. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates resulted, respectively, in more and less cells per zone and in increased and decreased bone growth rates. The FE model correctly reflected the development of a growth plate and the rate of bone growth in the femur. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates reflected growth plate pathologies and growth plates in PTHrP-/- and Ihh-/- mice. The three growth factors, PTHrP, Ihh and VEGF, could potentially together regulate tissue differentiation. [Copyright &y& Elsevier]

Objective: Tissue engineering is a promising method to treat damaged cartilage. So far it has not been possible to create tissue-engineered cartilage with an appropriate structural organization. It is envisaged that cartilage tissue engineering will significantly benefit from knowledge of how the collagen fiber orientation is directed by mechanical conditions. The goal of the present study is to evaluate whether a collagen remodeling algorithm based on mechanical loading can be corroborated by the collagen orientation in healthy cartilage.Methods: According to the remodeling algorithm, collagen fibrils align with a preferred fibril direction, situated between the positive principal strain directions. The remodeling algorithm was implemented in an axisymmetric finite element model of the knee joint. Loading as a result of typical daily activities was represented in three different phases: rest, standing and gait.Results: In the center of the tibial plateau the collagen fibrils run perpendicular to the subchondral bone. Just below the articular surface they bend over to merge with the articular surface. Halfway between the center and the periphery, the collagen fibrils bend over earlier, resulting in a thicker superficial and transitional zones. Near the periphery fibrils in the deep zone run perpendicular to the articular surface and slowly bend over to angles of -45 degrees and +45 degrees with the articular surface.Conclusion: The collagen structure as predicted with the collagen remodeling algorithm corresponds very well with the collagen structure in healthy knee joints. This remodeling algorithm is therefore considered to be a valuable tool for developing loading protocols for tissue engineering of articular cartilage. [ABSTRACT FROM AUTHOR]