Is zeaxanthin needed for desiccation tolerance? Sustained forms of thermal dissipation in tolerant versus sensitive bryophytes.

Desiccation tolerant (DT) plants engage and disengage sustained forms of energy dissipation in response to desiccation and rehydration. This project sought to characterize the role of zeaxanthin and thylakoid protein phosphorylation status in sustained energy dissipation during desiccation in bryophytes with varying DT. Tolerant (Polytrichum piliferum, Dicranum species, Calliergon stramineum) and sensitive (Grimmia species, Schistidium rivulare, Sphagnum species) moss were desiccated in darkness or natural light conditions for up to three weeks. Desiccation caused pronounced reductions in Fv /Fm in all cases which was enhanced by light exposure during desiccation. Desiccation in darkness resulted in no accumulation of Z in any species, however, in natural light conditions there was significant accumulation of Z in tolerant but not sensitive species. Desiccation in natural light, relative to darkness, resulted in more pronounced reductions in Fo in tolerant but not sensitive species. Recovery of Fv /Fm upon rehydration occurred in two phases, a rapid phase (minutes) and a slower phase (hours). Increased time of desiccation, and light exposure, resulted in a reduction in the rapid phase. Desiccation in light conditions resulted in some accumulation of the phosphorylated form of the major light harvesting trimer (LHCII). Data are consistent with two mechanisms of sustained quenching, neither of which requires Z. However, when desiccation occurs in natural light conditions, accumulation of Z likely contributes to one or both of the sustained forms of dissipation. Increases in LHCII phosphorylation during desiccation are consistent with increased connectivity between the photosystems. The absence of Z formation in sensitive species may contribute to their lack of desiccation tolerance.

Epigenetically mediated spontaneous reduction of NFAT1 expression causes imbalanced metabolic activities of articular chondrocytes in aged mice.

OBJECTIVE: Abnormal metabolic activities of chondrocytes may cause articular cartilage (AC) degradation, but key transcription factors regulating metabolic activities in AC of aging individuals remain unknown. This study aimed to investigate the role of transcription factor NFAT1 in regulating the expression of anabolic and catabolic molecules in AC of aged mice. METHODS: The hip, knee, and shoulder joints of BALB/c mice were harvested at 6, 12, 15, 18, and 24 months of age for histopathological and immunohistochemical (IHC) analyses. Total RNA was isolated from AC for gene expression. Genomic DNA and chromatin were prepared from AC for methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP) assays. RESULTS: NFAT1 expression in AC of mice was significantly decreased after 12 months of age, which was associated with reduced proteoglycan staining, decreased expression of chondrocyte markers, and increased expression of interleukin-1ß. Forced Nfat1 expression in chondrocytes from aged mice significantly reversed the abnormal metabolic activities. ChIP assays confirmed that NFAT1 bound to the promoter of the Acan, Col2a1, Col9a1, Col11a1, Il1b, Mmp13 and Tnfa genes in articular chondrocytes of aged mice. ChIP and MeDIP assays revealed that reduced NFAT1 expression in AC of aged mice was regulated by epigenetic histone methylation at the promoter region and was correlated with increased DNA methylation at introns 1 and 10 of the Nfat1 gene. CONCLUSION: NFAT1 is a transcriptional regulator of multiple anabolic and catabolic genes in AC of aged mice. Epigenetically mediated reduction of NFAT1 expression causes imbalanced metabolic activities of articular chondrocytes in aged mice.

Ageing modifies the effects of beetroot juice supplementation on 24-hour blood pressure variability: An individual participant meta-analysis.

OBJECTIVES: Abnormal circadian oscillations of blood pressure (BP) and nocturnal-diurnal BP differences (i.e., dipping) increase cardiovascular risk. Whether inorganic nitrate supplementation influences 24-hr BP variability is currently unknown. We studied the effects of high-nitrate beetroot juice supplementation on BP variability measured by 24-hr ambulatory BP monitoring (24-hr ABPM) in older subjects. METHODS: Data from four independent randomised clinical trials were collated. Eighty-five older participants (age range: 55-76 years) were included in the final database. Two trials had an open-label, parallel design and two trials had a cross-over, double-blind design. Participants were randomised to either beetroot juice or placebo. Changes in 24-hr ABPM (daily, diurnal, nocturnal), variability (weighted-SDs), night-dipping, morning surge for systolic and diastolic BP were measured. Meta-analysis was conducted to obtain pooled estimates of the effect size for each BP outcome. Sub-group analyses were conducted to evaluate the influence of age, BMI, gender, BP status and changes in nitrite concentrations on the effect size. RESULTS: The pooled effect of beetroot juice on all BP outcomes was not significant. Beetroot juice ingestion determined a significant decrease in nocturnal systolic BP variability in subjects aged less than 65 y (2.8 mmHg, -4.5 -1.0, p = 0.002) compared to the older group (≥ 65 y; 1.0 mmHg, -2.2 4.2, p = 0.54). A greater change in NO2(-) concentrations after beetroot supplementation was associated with significant differences for nocturnal mean (-3.4 mmHg, -0.6 -2.4, p = 0.02) and variability (-0.8 mmHg, -1.5 -0.06, p = 0.03) of systolic BP. CONCLUSIONS: The vascular responsiveness to inorganic nitrate may be modified by mechanisms of vascular ageing influencing the reducing capacity to convert inorganic nitrate into nitrite and tissue-specific responses to dietary nitrate supplementation.

Do contaminants compromise the use of recycled nutrients in organic agriculture? A review and synthesis of current knowledge on contaminant concentrations, fate in the environment and risk assessment.

Use of nutrients recycled from societal waste streams in agriculture is part of the circular economy, and in line with organic farming principles. Nevertheless, diverse contaminants in waste streams create doubts among organic farmers about potential risks for soil health. Here, we gather the current knowledge on contaminant levels in waste streams and recycled nutrient sources, and discuss associated risks. For potentially toxic elements (PTEs), the input of zinc (Zn) and copper (Cu) from mineral feed supplements remains of concern, while concentrations of PTEs in many waste streams have decreased substantially in Europe. The same applies to organic contaminants, although new chemical groups such as flame retardants are of emerging concern and globally contamination levels differ strongly. Compared to inorganic fertilizers, application of organic fertilizers derived from human or animal feces is associated with an increased risk for environmental dissemination of antibiotic resistance. The risk depends on the quality of the organic fertilizers, which varies between geographical regions, but farmland application of sewage sludge appears to be a safe practice as shown by some studies (e.g. from Sweden). Microplastic concentrations in agricultural soils show a wide spread and our understanding of its toxicity is limited, hampering a sound risk assessment. Methods for assessing public health risks for organic contaminants must include emerging contaminants and potential interactions of multiple compounds. Evidence from long-term field experiments suggests that soils may be more resilient and capable to degrade or stabilize pollutants than often assumed. In view of the need to source nutrients for expanding areas under organic farming, we discuss inputs originating from conventional farms vs. non-agricultural (i.e. societal) inputs. Closing nutrient cycles between agriculture and society is feasible in many cases, without being compromised by contaminants, and should be enhanced, aided by improved source control, waste treatment and sound risk assessments.

[Thalamic infarction following paradoxical embolism during total hip replacement : Case report and pathophysiological considerations]. / Thalamusinfarkt nach paradoxer Embolie bei Hüftgelenkersatz in unauffälliger Allgemeinanästhesie und Seitlagerung : Falldarstellung und pathophysiologische Überlegungen.

Because of a painful right-sided coxarthrosis a 57-year-old female patient underwent a cementless total arthroplasty under general anesthesia. Except for Asperger's syndrome and an occlusion of a vein in her left eye she stated no other diseases or complaints, especially no cardiac problems. Postoperatively she developed neurological symptoms of left-sided hemiparesis and hemihypesthesia. A cranial computer tomography was performed and a right-sided infarction of the thalamic region was found. A patent foramen ovale (PFO) and atrial septal aneurysm were detected 5 days later. The incidence of a PFO is given as 25% of the population. A paradoxical air embolism in the presence of a PFO is a feared complication in neurosurgical interventions in a semi-sitting or sitting position. Corpuscular emboli, such as bone, cement, fat or wound debris may be the reason for paradoxical embolisms in combination especially with partial or total hip replacement. The kind of embolism in the case described could not be clarified. Deep vein thrombosis or cardiac arrhythmia could be excluded. Therefore, it can be considered most likely that the operation site was the source of the embolism. The trigger for a paradoxical embolism is a reversal of the pressure difference between the right and left atria: normally the left atrial pressure exceeds the right atrial pressure by ca. 2-4 mm Hg, resulting possibly in a small clinically irrelevant left-to-right shunt. If the pulmonary arterial circulation is compromised and pulmonary vascular resistance increases, the pressure gradient between the left and right atria reverses and a right-to-left shunt can occur causing a paradoxical embolism. Positive end-expiratory pressure (PEEP) ventilation during anesthesia could be an important reason for a shunt reversal between the right and left atria and therefore favoring a paradoxical embolism but the pathophysiological role of PEEP has not yet been finally clarified.

[Meralgia paraesthetica as complication of patient positioning : A not fully controllable risk]. / Meralgia paraesthetica als Lagerungsschaden : Kein voll beherrschbares Risiko.

Meralgia paraesthetica (MP) is the consequence of an entrapment or stretch injury of the lateral femoral cutaneous nerve at the crossing region with the inguinal ligament where the nerve exits the pelvis. It results in temporary or permanent sensory loss, paraesthesia and pain in the anterolateral region of the thigh. Idiopathic forms are known for example as seat belt syndrome or jeans syndrome. An MP can also occur as a complication of surgical or intensive care patient positioning. In focus are the lithotomy position, prone position and beach chair position.We analyzed 21 complaints about MP occurring for the first time postoperatively, which had been submitted to the expert committee for medical treatment errors at the North Rhine Medical Association over the past 10 years. Among these, six cases could be identified as positioning damage after a lithotomy position. In three cases MP occurred after supine positioning but the etiology could not be clarified with certainty. In 12 cases MP was recognized as a direct surgical complication.The pathophysiology, incidence and course as well as legal implications of position-related MP are discussed. Pressure damage to the nerve at its intersection with the inguinal ligament is assumed to be the main pathomechanism. Although all the cases presented here occurred after lithotomy positioning, the complication also appears to occur with other types of positioning according to the literature data, the most common being prone positioning. This also explains the increasingly published case reports of MP after prone positioning in COVID-19 patients for respiratory treatment. Safe avoidance of the positioning-related complication does not appear to be possible due to the anatomical variability of the course of the nerve and the unclear pathomechanisms.

OARSI-FDA initiative: defining the disease state of osteoarthritis.

OBJECTIVE: To respond to a pre-specified set of questions posed by the United States Food and Drug Administration (FDA) on defining the disease state to inform the clinical development of drugs, biological products, and medical devices for the prevention and treatment of osteoarthritis (OA). METHODS: An Osteoarthritis Research Society International (OARSI) Disease State working group was established, comprised of representatives from academia and industry. The Working Group met in person and by teleconference on several occasions from the Spring of 2008 through the Autumn of 2009 to develop consensus-based, evidence-informed responses to these questions. A report was presented at a public forum in December 2009 and accepted by the OARSI Board of Directors in the Summer of 2010. RESULTS: An operational definition of OA was developed incorporating current understanding of the condition. The structural changes that characterize OA at the joint level were distinguished from the patients' experience of OA as the 'disease' and 'illness', respectively. Recommendations were made regarding the evaluation of both in future OA clinical trials. The current poor understanding of the phenotypes that characterize OA was identified as an important area for future research. CONCLUSIONS: The design and conduct of clinical trials for new OA treatments should address the heterogeneity of the disease, treatment-associated structural changes in target joints and patient-reported outcomes.

Change in regional cartilage morphology and joint space width in osteoarthritis participants versus healthy controls: a multicentre study using 3.0 Tesla MRI and Lyon-Schuss radiography.

OBJECTIVE: Cartilage morphology displays sensitivity to change in osteoarthritis (OA) with quantitative MRI (qMRI). However, (sub)regional cartilage thickness change at 3.0 Tesla (T) has not been directly compared with radiographic progression of joint space narrowing in OA participants and non-arthritic controls. METHODS: A total of 145 women were imaged at 7 clinical centres: 86 were non-obese and asymptomatic without radiographic OA and 55 were obese with symptomatic and radiographic OA (27 Kellgren-Lawrence grade (KLG)2 and 28 KLG3). Lyon-Schuss (LS) and fixed flexion (FF) radiographs were obtained at baseline, 12 and 24 months, and coronal spoiled gradient echo MRI sequences at 3.0 T at baseline, 6, 12 and 24 months. (Sub)regional, femorotibial cartilage thickness and minimum joint space width (mJSW) in the medial femorotibial compartment were measured and the standardised response means (SRMs) determined. RESULTS: At 6 months, qMRI demonstrated a -3.7% "annualised" change in cartilage thickness (SRM -0.33) in the central medial femorotibial compartment (cMFTC) of KLG3 subjects, but no change in KLG2 subjects. The SRM for mJSW in 12-month LS/FF radiographs of KLG3 participants was -0.68/-0.13 and at 24 months was -0.62/-0.20. The SRM for cMFTC changes measured with qMRI was -0.32 (12 months; -2.0%) and -0.48 (24 months; -2.2%), respectively. CONCLUSIONS: qMRI and LS radiography detected significant change in KLG3 participants at high risk of progression, but not in KLG2 participants, and only small changes in controls. At 12 and 24 months, LS displayed greater, and FF less, sensitivity to change in KLG3 participants than qMRI.

Varus malalignment negates the structure-modifying benefits of doxycycline in obese women with knee osteoarthritis.

OBJECTIVE: To estimate the extent to which varus malalignment, a source of abnormal intra-articular stresses in the medial tibiofemoral compartment and risk factor for progression of knee osteoarthritis (OA), may have diminished the structure-modifying benefit of doxycycline in knee OA. METHODS: Post hoc treatment group comparisons from a randomized, placebo-controlled trial of the effect of doxycycline (100mg, twice daily) on medial joint space narrowing (JSN) in subgroups of varus and non-varus OA knees. Subjects (N=379 with X-ray follow-up) were obese 45-64-year-old women with unilateral knee OA at baseline. JSN was measured manually in semiflexed anteroposterior (AP) radiographs acquired with standardized fluoroscopic positioning. The anatomic-axis angle (AAA) was measured in each baseline radiograph and transformed to an estimate of the mechanical-axis angle (MAA(est)) using a validated regression equation. Knees with MAA(est)<178 degrees were classified as varus. RESULTS: In our original comparison with placebo, doxycycline slowed the rate of medial JSN in OA knees by 38% at 16 months and by 33% at 30 months. Among non-varus OA knees, 16-month JSN in the doxycycline group was 44% slower than in the placebo group (0.09 vs 0.16 mm/year, P=0.080), and 39% slower at month 30 (0.10 vs 0.17 mm/year, P=0.026). JSN in varus knees (0.20-0.27 mm/year) was more rapid than in non-varus knees (P=0.083) and unaffected by doxycycline. CONCLUSION: Varus malalignment negated the slowing of structural progression of medial-compartment OA by doxycycline. To our knowledge, this is the first report documenting that static varus angulation can negate a pharmacologic structure-modifying effect.

Alignment of the medial tibial plateau affects the rate of joint space narrowing in the osteoarthritic knee.

OBJECTIVE: To determine, in serial fixed-flexion (FF) radiographs of subjects with knee osteoarthritis (KOA), the importance of, and basis for, the effect of alignment of the medial tibial plateau (MTP), as determined by the inter-margin distance (IMD), on joint space narrowing (JSN). METHODS: Baseline and 12-month X-rays of 590 knees with Kellgren and Lawrence grade (KLG) 2/3 OA from the public-release dataset of the Osteoarthritis Initiative (OAI) were assigned to subgroups based upon IMD at baseline (IMD(BL)) and the difference between IMD(BL) and IMD(12 mos). Relationships of JSN to IMD(BL) and to the difference between IMD(BL and) IMD(12 mos) were evaluated. RESULTS: In all 590 knees, mean JSN was 0.13 ± 0.51 mm (P<0.0001) and MTP alignment and replication of IMD(BL) in the 12-month film were, in general, poor. JSN was significantly (P=0.012) more rapid in Subgroup A (IMD≤1.70 mm at both time points) than in Subgroup B (both IMDs>1.70 mm): 0.15 ± 0.43; 0.08 ± 0.47. Within Subgroup B we identified a subset, Subgroup B1, in which, although alignment was poor at both time points, the large IMD(BL) was, by chance, highly reproduced by IMD(12 mos) (difference between the two IMDs=0.01 ± 0.27 mm, NS). JSN in Subgroup B1 was 0.06 ± 0.41 mm and did not differ from that in other knees of Subgroup B (P=0.87). The standardized response mean (SRM) in all 590 knees and Subgroups A, B and B1 was 0.25, 0.34, 0.17 and 0.06, respectively. Independent of IMD(BL), JSN correlated significantly with the difference between the IMDs in the two radiographs (r=0.17, P=0.0001). CONCLUSION: Skewed MTP alignment in serial films and poor replication of IMD(BL) in the follow-up exam affect JSN measurement. The magnitude of change in joint space width (JSW) related to the poor quality of alignment that is common with the FF view jeopardizes accurate evaluation of JSN.

OARSI recommendations for the management of hip and knee osteoarthritis: part III: Changes in evidence following systematic cumulative update of research published through January 2009.

OBJECTIVE: To update evidence for available therapies in the treatment of hip and knee osteoarthritis (OA) and to examine whether research evidence has changed from 31 January 2006 to 31 January 2009. METHODS: A systematic literature search was undertaken using MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index and the Cochrane Library. The quality of studies was assessed. Effect sizes (ESs) and numbers needed to treat were calculated for efficacy. Relative risks, hazard ratios (HRs) or odds ratios were estimated for side effects. Publication bias and heterogeneity were examined. Sensitivity analysis was undertaken to compare the evidence pooled in different years and different qualities. Cumulative meta-analysis was used to examine the stability of evidence. RESULTS: Sixty-four systematic reviews, 266 randomised controlled trials (RCTs) and 21 new economic evaluations (EEs) were published between 2006 and 2009. Of 51 treatment modalities, new data on efficacy have been published for more than half (26/39, 67%) of those for which research evidence was available in 2006. Among non-pharmacological therapies, ES for pain relief was unchanged for self-management, education, exercise and acupuncture. However, with new evidence the ES for pain relief for weight reduction reached statistical significance, increasing from 0.13 [95% confidence interval (CI) -0.12, 0.36] in 2006 to 0.20 (95% CI 0.00, 0.39) in 2009. By contrast, the ES for electromagnetic therapy which was large in 2006 (ES=0.77, 95% CI 0.36, 1.17) was no longer significant (ES=0.16, 95% CI -0.08, 0.39). Among pharmacological therapies, the cumulative evidence for the benefits and harms of oral and topical non-steroidal anti-inflammatory drugs, diacerhein and intra-articular (IA) corticosteroid was not greatly changed. The ES for pain relief with acetaminophen diminished numerically, but not significantly, from 0.21 (0.02, 0.41) to 0.14 (0.05, 0.22) and was no longer significant when analysis was restricted to high quality trials (ES=0.10, 95% CI -0.0, 0.23). New evidence for increased risks of hospitalisation due to perforation, peptic ulceration and bleeding with acetaminophen >3g/day have been published (HR=1.20, 95% CI 1.03, 1.40). ES for pain relief from IA hyaluronic acid, glucosamine sulphate, chondroitin sulphate and avocado soybean unsponifiables also diminished and there was greater heterogeneity of outcomes and more evidence of publication bias. Among surgical treatments further negative RCTs of lavage/debridement were published and the pooled results demonstrated that benefits from this modality of therapy were no greater than those obtained from placebo. CONCLUSION: Publication of a large amount of new research evidence has resulted in changes in the calculated risk-benefit ratio for some treatments for OA. Regular updating of research evidence can help to guide best clinical practice.

Copper toxicity to bioluminescent Nitrosomonas europaea in soil is explained by the free metal ion activity in pore water.

The terrestrial biotic ligand model (BLM) for metal toxicity in soil postulates that metal toxicity depends on the free metal ion activity in solution and on ions competing for metal sorption to the biotic ligand. Unequivocal evidence for the BLM assumptions is most difficult to obtain for native soil microorganisms because the abiotic and biotic compartments cannot be experimentally separated. Here, we report copper (Cu) toxicity to a bioluminescent Nitrosomonas europaea reporter strain that was used in a solid phase-contact assay and in corresponding soil extracts and artificial soil solutions. The Cu(2+) ion activities that halve bioluminescence (EC50) in artificial solutions ranged 10(-5) to 10(-7) M and increased with increasing activities of H(+), Ca(2+) and Mg(2+) according to the BLM concept. The solution based Cu(2+) EC50 values of N. europaea in six contaminated soils ranged 2 × 10(-6) to 2 × 10(-9) M and these thresholds for both solid phase or soil extract based assays were well predicted by the ion competition model fitted to artificial solution data. In addition, solution based Cu(2+) EC50 of the solid phase-contact assay were never smaller than corresponding values in soil extracts suggesting no additional solid phase toxic route. By restricting the analysis to the same added species, we show that the Cu(2+) in solution represents the toxic species to this bacterium.

Correlation of mass fractal dimension and cluster size of silica in styrene butadiene rubber composites.

The morphology of the precipitated silica VN3 filled in styrene butadiene rubber was studied as a function of the volume fraction Φ by means of small-angle X-ray scattering experiments. The wide q-range of 0.008 nm(-1)

Do the effects of cannabis on the hippocampus and striatum increase risk for psychosis?

Cannabis use is associated with increased risk of psychotic symptoms and in a small number of cases it can lead to psychoses. This review examines the neurobiological mechanisms that mediate the link between cannabis use and psychosis risk. We use an established preclinical model of psychosis, the methylazoxymethanol acetate (MAM) rodent model, as a framework to examine if psychosis risk in some cannabis users is mediated by the effects of cannabis on the hippocampus, and this region's role in the regulation of mesolimbic dopamine. We also examine how cannabis affects excitatory neurotransmission known to regulate hippocampal neural activity and output. Whilst there is clear evidence that cannabis/cannabinoids can affect hippocampal and medial temporal lobe function and structure, the evidence that cannabis/cannabinoids increase striatal dopamine function is less robust. There is limited evidence that cannabis use affects cortical and striatal glutamate levels, but there are currently too few studies to draw firm conclusions. Future work is needed to test the MAM model in relation to cannabis using multimodal neuroimaging approaches.

Progressive increase in body mass index is not associated with a progressive increase in joint space narrowing in obese women with osteoarthritis of the knee.

OBJECTIVE: Given that obesity is a risk factor for osteoarthritis (OA) of the knee, a study was undertaken to determine whether progressively higher body mass index (BMI) among obese women is associated with progressive increases in joint space narrowing (JSN). METHODS: Medial compartment JSN over 12 months in Lyon Schuss radiographs of 60 obese women (BMI 30.0-50.5 kg/m(2)) with radiographic and symptomatic OA was compared with that in 81 non-obese women (BMI <28 kg/m(2)) with normal radiographs and minimal or no symptoms of knee OA. RESULTS: Among the patients with OA, higher BMI tended to be associated with a higher Kellgren and Lawrence (KL) grade of OA severity. JSN in the non-obese controls was negligible, but in the 30 patients with KL grade 2 and KL grade 3 knees, mean (SD) JSN was 0.12 (0.31) mm and 0.32 (0.50) mm, respectively (p<0.005 and p<0.001). No association was seen between baseline BMI and 12-month JSN in patients with OA; indeed, the regression plot suggested a slight inverse relationship between the two. CONCLUSIONS: In obese patients with OA, progressively higher BMI values were not accompanied by a progressively increasing rate of JSN. Joint loading was not evaluated, but it is possible that marked obesity limited the functional capacity of some subjects with OA, protecting their knees from loading. For investigators considering eligibility criteria for a trial of a structure-modifying OA drug, these data suggest that recruitment of patients with a BMI much higher than 30 kg/m(2) will not enrich the sample of subjects who will have more rapid JSN than those with a BMI of only 30 kg/m(2).

Reproducibility and sensitivity to change of a new method of computer measurement of joint space width in hip osteoarthritis. Performance of three radiographic views obtained at a 3-year interval.

BACKGROUND: Measurement of radiographic joint space width (JSW) and of joint space narrowing (JSN) is the currently recommended method for assessment of anatomical severity and structural progression of osteoarthritis (OA), respectively. A standard radiographic view of the pelvis is commonly used for measurement of hip OA but other views are available. OBJECTIVES: To evaluate the inter-intra reader reproducibility and the sensitivity to change of a new automated method of measurement of the hip JSW and to assess which radiographic view [pelvis anteroposterior (AP) view, hip AP view, hip oblique view] provides the greatest accuracy for JSW and JSN measurements. MATERIAL AND METHODS: An AP pelvis radiograph, an AP radiograph centered on the target hip (AP hip) and an oblique view were performed at baseline (M0) and 3 years later (M36) in 50 hip OA patients. Two readers, blinded to each other's results and time sequence, measured twice, at a minimum 15 day interval, the six radiographs of each patient, using a novel version of a previously validated software program whose edge-based algorithm automatically detects the joint space contours. Inter-observer cross-sectional (M0+M36) and longitudinal (M0-M36) reproducibility of JSW measurement was assessed by the intra-class correlation coefficient (ICC) and the Bland-Altman method. Sensitivity to change was estimated by the standardized response mean (SRM). An ANOVA was used to analyze differences related to the observer and the view. RESULTS: Intra-observer reproducibility: For JSW measurement, the ICC value, for observers 1 and 2 respectively, were 0.92 and 0.83 for the pelvic view, 0.96 and 0.88 for the hip AP view, and 0.90 and 0.86 for the oblique view. For JSN, ICC was 0.94 and 0.82 for the pelvic view, 0.97 and 0.78 for the hip AP view, and 0.95 and 0.86 for the oblique view. Inter-observer reproducibility: For JSW measurement, ICC was 0.87 for the pelvic view, 0.98 for the hip AP view, and 0.87 for the oblique view. The mean inter-observer difference (SD) was 0.0 (0.31), -0.01 (0.15) and -0.04 (0.4)mm for pelvic, AP and oblique views respectively. For JSN, ICC was 0.91 for the pelvic view, 0.93 for the hip AP view, and 0.90 for the oblique view. Sensitivity to change: SRM values were 0.61 (observer 1) and 0.65 (observer 2) for the pelvic view, 0.68 and 0.75, respectively, for the hip AP view, 0.64 and 0.66, respectively, for the oblique view. JSN did not vary significantly with the observer and the view. In 27% of cases intervention by the observer was necessary to correct the computer's identification of the acetabular edge in the area of interest. CONCLUSION: Computer measurement of the radiographic hip joint space provided good intra- and inter-observer reproducibility and good sensitivity to change. However, it was necessary for the observer to intervene frequently to select the area of interest and adjust detection of the bone edge. The hip AP view performed better than the pelvis and oblique views, but not significantly so.

Relation of regional articular cartilage morphometry and meniscal position by MRI to joint space width in knee radiographs.

OBJECTIVE: To ascertain the contribution of articular cartilage morphometry and meniscal position on MRI to joint space width (JSW) measured in the Lyon schuss radiograph of the knee. DESIGN: 62 obese women with knee OA and 99 non-obese female controls (mean age 56.6 years) were imaged using 3T MRI and coronal water excitation spoiled gradient echo sequences. Segmentation of femorotibial cartilage morphology and regional morphometric analysis was performed using custom software. Meniscal position was measured quantitatively in sagittal and coronal planes. Minimum space width (mJSW) was measured in the Lyon Schuss knee radiograph; Kellgren and Lawrence grades (KLG) were assigned on standing anteroposterior knee films. The relative contribution of regional cartilage thickness and meniscal position to mJSW was assessed initially in univariate models and subsequently with multivariable modelling. RESULTS: 65% of the variation in mJSW was explained by regional cartilage thickness measures, different KLG and meniscal coverage. Of these measures the medial tibia cartilage thickness measures and central region of the central medial femur (ccMF) play a consistent role in variations in mJSW observed across all KLG. Further ccMF and the addition of percent meniscal coverage to this model explains the remaining differences in mean mJSW found between those subjects with definite joint space narrowing (KLG3) and those without OA. CONCLUSION: The variation in radiographic mJSW is best described by five regional cartilage thickness measures and percent meniscal coverage. The magnitude of each measures contribution differs according to radiographic severity with more variability explained by cartilage thickness of ccMF cartilage thickness and percent meniscal coverage with more severe disease.

OARSI-OMERACT definition of relevant radiological progression in hip/knee osteoarthritis.

BACKGROUND: Joint space width (JSW) evaluated in millimeters on plain X-rays is the currently optimal recognized technique to evaluate osteoarthritis (OA) structural progression. Data obtained can be presented at the group level (e.g., mean+/-standard deviation of the changes). Such presentation makes difficult the interpretation of the clinical relevance of the reported results. Therefore, a presentation at the individual level (e.g., % progressors) seems more attractive but requires to determining a cut-off. Several methodologies have been proposed to define cut-offs in JSW: arbitrary chosen cut-off, cut-off based on the validity to predict a relevant end-point such as the requirement of total articular replacement or cut-off based on the measurement error such as smallest detectable difference (SDD). OBJECTIVES: The objective of this OARSI-OMERACT initiative was to define a cut-off evaluated in millimeters on plain X-rays above which a change in JSW could be considered as relevant in patients with hip and knee OA. METHODS: The first step consisted in a systematic literature research performed using Medline database up to July 2007 to obtain all manuscripts published between 1990 and 2007 reporting a cut-off value in JSW evaluated in millimeters at either the knee or hip level. The second step consisted in a consensus based on the best knowledge of the 11 experts with the support of the available evidence. RESULTS: Among the 506 articles selected by the search, 47 articles reported cut-off of JSW in millimeters. There was a broad heterogeneity in cut-off values, whatever the methodologies or the OA localization considered (e.g., from 0.12 to 0.84 mm and from 0.22 to 0.78 mm for Knee (seven studies) and hip (seven studies), respectively when considering the data obtained based on the reliability). Based on the data extracted in the literature, the expert committee proposed a definition of relevant change in JSW based on plain X-rays, on an absolute change of JSW in millimeters and on the measurement error e.g., calculation of the SDD using the Bland and Altman technique. The results of the analysis of JSW should be expressed in terms of a dichotomous variable (e.g., progressors yes/no): a patient with a change in JSW during the study over such SDD will fulfill the definition of "progressor". Moreover, the pilot study aimed at evaluating the measurement error should be designed to reflect the different characteristics of the primary study in which the analysis of the radiological findings will be based on (patient's characteristics, centers characteristics, readers). CONCLUSION: This initiative based on both an Evidence Based Medicine (Systematic Literature Research) and Expert Opinion approach resulted in a proposal of definition of relevant radiological progression in OA to be used as end-point in clinical trials and also recommendations on the conduct of the reliability study allowing such definition.

Subregional femorotibial cartilage morphology in women--comparison between healthy controls and participants with different grades of radiographic knee osteoarthritis.

OBJECTIVE: To identify subregional differences in femorotibial cartilage morphology between healthy controls and women with different grades of radiographic knee osteoarthritis (OA). DESIGN: 158 women aged > or =40 years were studied. Weight-bearing extended anterior-posterior (AP) and Lyon schuss radiographs were obtained and the Kellgren Lawrence grade (KLG) determined. 97 women had a body mass index (BMI)< or =28, no symptoms, and were AP KLG0. 61 women had a BMI> or =30, symptoms in the target knee, and mild (KLG2=31) to moderate (KLG3=30) medial femorotibial radiographic OA in the AP views. Coronal spoiled gradient echo water excitation sequences were acquired at 3.0 Tesla. Total plate and regional measures of cartilage morphology of the weight-bearing femorotibial joint were quantified. RESULTS: KLG2 participants displayed, on average, thicker cartilage than healthy controls in the medial femorotibial compartment (particularly anterior subregion of the medial tibia (MT) and peripheral [external, internal] subregions of the medial femur), and in the lateral femur. KLG3 participants displayed significantly thinner cartilage than KLG0 participants in the medial weight-bearing femur (central subregion), in the external subregion of the MT, and in the internal subregion of the lateral tibia. These differences were generally unaffected when possible effects of demographic covariates were considered. CONCLUSIONS: The results indicate that in femorotibial OA regional cartilage thickening and thinning may occur, dependent on the (radiographic) disease status of the joint. These changes appear to display a heterogeneous spatial pattern, where certain subregions are more strongly affected than others.

[The 100th anniversary of the birthday of Virginia Apgar. In honor of the developer of the Apgar score]. / Zum 100. Geburtstag von Virginia Apgar. Würdigung der Entwicklerin des Apgar-Scores.

The 7th of June 2009 marks the 100th anniversary of the birthday of the American anaesthesiologist Virginia Apgar. The Apgar score for evaluation of the newborn created by her in 1952 and later named after her is one of the most popular and most often used medical scoring systems.