Identification of Therapeutic Targets of Inflammatory Monocyte Recruitment to Modulate the Allogeneic Injury to Donor Cornea

Purpose: We sought to test the hypothesis that monocytes contribute to the immunopathogenesis of corneal allograft rejection and identify therapeutic targets to inhibit monocyte recruitment. Methods: Monocytes and proinflammatory mediators within anterior chamber samples during corneal graft rejection were quantified by flow cytometry and multiplex protein assays. Lipopolysaccharide or IFN-γ stimulation of monocyte-derived macrophages (MDMs) was used to generate inflammatory conditioned media (CoM). Corneal endothelial viability was tested by nuclear counting, connexin 43, and propidium iodide staining. Chemokine and chemokine receptor expression in monocytes and MDMs was assessed in microarray transcriptomic data. The role of chemokine pathways in monocyte migration across microvascular endothelium was tested in vitro by chemokine depletion or chemokine receptor inhibitors. Results: Inflammatory monocytes were significantly enriched in anterior chamber samples within 1 week of the onset of symptoms of corneal graft rejection. The MDM inflammatory CoM was cytopathic to transformed human corneal endothelia. This effect was also evident in endothelium of excised human cornea and increased in the presence of monocytes. Gene expression microarrays identified monocyte chemokine receptors and cognate chemokines in MDM inflammatory responses, which were also enriched in anterior chamber samples. Depletion of selected chemokines in MDM inflammatory CoM had no effect on monocyte transmigration across an endothelial blood–eye barrier, but selective chemokine receptor inhibition reduced monocyte recruitment significantly. Conclusions: We propose a role for inflammatory monocytes in endothelial cytotoxicity in corneal graft rejection. Therefore, targeting monocyte recruitment offers a putative novel strategy to reduce donor endothelial cell injury in survival of human corneal allografts

Disentangling manual muscle testing and Applied Kinesiology: critique and reinterpretation of a literature review

Cuthbert and Goodheart recently published a narrative review on the reliability and validity of manual muscle testing (MMT) in the Journal. The authors should be recognized for their effort to synthesize this vast body of literature. However, the review contains critical errors in the search methods, inclusion criteria, quality assessment, validity definitions, study interpretation, literature synthesis, generalizability of study findings, and conclusion formulation that merit a reconsideration of the authors' findings. Most importantly, a misunderstanding of the review could easily arise because the authors did not distinguish the general use of muscle strength testing from the specific applications that distinguish the Applied Kinesiology (AK) chiropractic technique. The article makes the fundamental error of implying that the reliability and validity of manual muscle testing lends some degree of credibility to the unique diagnostic procedures of AK. The purpose of this commentary is to provide a critical appraisal of the review, suggest conclusions consistent with the literature both reviewed and omitted, and extricate conclusions that can be made about AK in particular from those that can be made about MMT. When AK is disentangled from standard orthopedic muscle testing, the few studies evaluating unique AK procedures either refute or cannot support the validity of AK procedures as diagnostic tests. The evidence to date does not support the use of MMT for the diagnosis of organic disease or pre/subclinical conditions

Illustrating risk difference and number needed to treat from a randomized controlled trial of spinal manipulation for cervicogenic headache

<p>Abstract</p> <p>Background</p> <p>The number needed to treat (NNT) for one participant to benefit is considered a useful, clinically meaningful way of reporting binary outcomes from randomized trials. Analysis of continuous data from our randomized controlled trial has previously demonstrated a significant and clinically important difference favoring spinal manipulation over a light massage control.</p> <p>Methods</p> <p>Eighty participants were randomized to receive spinal manipulation or a light massage control (n = 40/group). Improvements in cervicogenic headache pain (primary outcome), disability, and number in prior four weeks were dichotomized into binary outcomes at two thresholds: 30% representing minimal clinically important change and 50% representing clinical success. Groups were compared at 12 and 24-week follow-up using binomial regression (generalized linear models) to compute the adjusted risk difference (RD) between groups and number needed to treat (NNT) after adjusting for baseline differences between groups. Results were compared to logistic regression results.</p> <p>Results</p> <p>For headache pain, clinically important improvement (30% or 50%) was more likely for spinal manipulation: adjusted RD = 17% to 27% and NNT = 3.8 to 5.8 (p = .005 to .028). Some statistically significant results favoring manipulation were found for headache disability and number.</p> <p>Conclusion</p> <p>Spinal manipulation demonstrated a benefit in terms of a clinically important improvement of cervicogenic headache pain. The use of adjusted NNT is recommended; however, adjusted RD may be easier to interpret than NNT. The study demonstrated how results may depend on the threshold for dichotomizing variables into binary outcomes.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NLM identifier NCT00246350.</p

An investigation into the validity of cervical spine motion palpation using subjects with congenital block vertebrae as a 'gold standard'

BACKGROUND: Although the effectiveness of manipulative therapy for treating back and neck pain has been demonstrated, the validity of many of the procedures used to detect joint dysfunction has not been confirmed. Practitioners of manual medicine frequently employ motion palpation as a diagnostic tool, despite conflicting evidence regarding its utility and reliability. The introduction of various spinal models with artificially introduced 'fixations' as an attempt to introduce a 'gold standard' has met with frustration and frequent mechanical failure. Because direct comparison against a 'gold standard' allows the validity, specificity and sensitivity of a test to be calculated, the identification of a realistic 'gold standard' against which motion palpation can be evaluated is essential. The objective of this study was to introduce a new, realistic, 'gold standard', the congenital block vertebra (CBV) to assess the validity of motion palpation in detecting a true fixation. METHODS: Twenty fourth year chiropractic students examined the cervical spines of three subjects with single level congenital block vertebrae, using two commonly employed motion palpation tests. The examiners, who were blinded to the presence of congenital block vertebrae, were asked to identify the most hypomobile segment(s). The congenital block segments included two subjects with fusion at the C2–3 level and one with fusion at C5-6. Exclusion criteria included subjects who were frankly symptomatic, had moderate or severe degenerative changes in their cervical spines, or displayed signs of cervical instability. Spinal levels were marked on the subject's skin overlying the facet joints from C1 to C7 bilaterally and the motion segments were then marked alphabetically with 'A' corresponding to C1-2. Kappa coefficients (K) were calculated to determine the validity of motion palpation to detect the congenitally fused segments as the 'most hypomobile' segments. Sensitivity and specificity of the diagnostic procedure were also calculated. RESULTS: Kappa coefficients (K) showed substantial overall agreement for identification of the segment of greatest hypomobility (K = 0.65), with substantial (K = 0.76) and moderate (K = 0.46) agreement for hypomobility at C2-3 and C5-6 respectively. Sensitivity ranged from 55% at the C5-6 CBV to 78% at the C2-3 level. Specificity of the procedure was high (91 – 98%). CONCLUSION: This study indicates that relatively inexperienced examiners are capable of correctly identifying inter-segmental fixations (CBV) in the cervical spine using 2 commonly employed motion palpation tests. The use of a 'gold standard' (CBV) in this study and the substantial agreement achieved lends support to the validity of motion palpation in detecting major spinal fixations in the cervical spine

Extragalactic Results from the Infrared Space Observatory

More than a decade ago the IRAS satellite opened the realm of external galaxies for studies in the 10 to 100 micron band and discovered emission from tens of thousands of normal and active galaxies. With the 1995-1998 mission of the Infrared Space Observatory the next major steps in extragalactic infrared astronomy became possible: detailed imaging, spectroscopy and spectro-photometry of many galaxies detected by IRAS, as well as deep surveys in the mid- and far- IR. The spectroscopic data reveal a wealth of detail about the nature of the energy source(s) and about the physical conditions in galaxies. ISO's surveys for the first time explore the infrared emission of distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is the role of star formation in the activity and evolution of galaxies.Comment: 106 pages, including 17 figures. Ann.Rev.Astron.Astrophys. (in press), a gzip'd pdf file (667kB) is also available at http://www.mpe.mpg.de/www_ir/preprint/annrev2000.pdf.g

Earliest Triassic microbialites in the South China Block and other areas; controls on their growth and distribution

Earliest Triassic microbialites (ETMs) and inorganic carbonate crystal fans formed after the end-Permian mass extinction (ca. 251.4 Ma) within the basal Triassic Hindeodus parvus conodont zone. ETMs are distinguished from rarer, and more regional, subsequent Triassic microbialites. Large differences in ETMs between northern and southern areas of the South China block suggest geographic provinces, and ETMs are most abundant throughout the equatorial Tethys Ocean with further geographic variation. ETMs occur in shallow-marine shelves in a superanoxic stratified ocean and form the only widespread Phanerozoic microbialites with structures similar to those of the Cambro-Ordovician, and briefly after the latest Ordovician, Late Silurian and Late Devonian extinctions. ETMs disappeared long before the mid-Triassic biotic recovery, but it is not clear why, if they are interpreted as disaster taxa. In general, ETM occurrence suggests that microbially mediated calcification occurred where upwelled carbonate-rich anoxic waters mixed with warm aerated surface waters, forming regional dysoxia, so that extreme carbonate supersaturation and dysoxic conditions were both required for their growth. Long-term oceanic and atmospheric changes may have contributed to a trigger for ETM formation. In equatorial western Pangea, the earliest microbialites are late Early Triassic, but it is possible that ETMs could exist in western Pangea, if well-preserved earliest Triassic facies are discovered in future work

Socioeconomic disparities in breast cancer survival: relation to stage at diagnosis, treatment and race

<p>Abstract</p> <p>Background</p> <p>Previous studies have documented lower breast cancer survival among women with lower socioeconomic status (SES) in the United States. In this study, I examined the extent to which socioeconomic disparity in breast cancer survival was explained by stage at diagnosis, treatment, race and rural/urban residence using the Surveillance, Epidemiology, and End Results (SEER) data.</p> <p>Methods</p> <p>Women diagnosed with breast cancer during 1998-2002 in the 13 SEER cancer registry areas were followed-up to the end of 2005. The association between an area-based measure of SES and cause-specific five-year survival was estimated using Cox regression models. Six models were used to assess the extent to which SES differences in survival were explained by clinical and demographical factors. The base model estimated the hazard ratio (HR) by SES only and then additional adjustments were made sequentially for: 1) age and year of diagnosis; 2) stage at diagnosis; 3) first course treatment; 4) race; and 5) rural/urban residence.</p> <p>Results</p> <p>An inverse association was found between SES and risk of dying from breast cancer (p < 0.0001). As area-level SES falls, HR rises (1.00 → 1.05 → 1.23 → 1.31) with the two lowest SES groups having statistically higher HRs. This SES differential completely disappeared after full adjustment for clinical and demographical factors (p = 0.20).</p> <p>Conclusion</p> <p>Stage at diagnosis, first course treatment and race explained most of the socioeconomic disparity in breast cancer survival. Targeted interventions to increase breast cancer screening and treatment coverage in patients with lower SES could reduce much of socioeconomic disparity.</p

Effects of whole-body vibration on postural control in elderly: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>This systematic review was performed to summarize the current evidence for whole body vibration (WBV) interventions on postural control in elderly.</p> <p>Methods</p> <p>English and German language papers in Medline, PEDro, Cinahl and the Cochrane databases were searched. Two reviewers extracted data on patients' characteristics, type of WBV intervention and outcomes. Two independent reviewers rated the methodological quality of these studies. Data were pooled using random-effects meta-analysis.</p> <p>Results</p> <p>Fifteen papers reporting quantitative data were included. Results from 15 papers could be pooled for a meta-analysis. The studies involved 933 participants. In 7 studies the authors investigated the effects of vibration plates generating vertical sinusoidal vibrations (VS-WBV) and 7 papers described the use of side-alternating sinusoidal vibrations (SS-WBV). One study investigated both VS-WBV and SS-WBV.</p> <p>Weak to moderate evidence of an overall effect as a result of VS-WBV and SS-WBV was observed for (a) static balance for post-intervention values with a standardized mean difference (SMD) -0.06, 95% CI -0.31 to 0.18 and for change values SMD -0.26, 95% CI -1.09 to 0.57, and (b) dynamic balance for post-intervention-values SMD -0.34, 95% CI -0.60 to -0.08. For functional balance (c) an overall outcome for post-intervention values with SMD of 0.34, 95% CI -0.19 to 0.87 was found.</p> <p>Conclusions</p> <p>The 15 studies reviewed were of moderate methodological quality. In summary, SS-WBV seems to have a beneficial effect on dynamic balance in elderly individuals. However, the current results should be interpreted with caution because of the observed heterogeneity of training parameters and statistical methods. Future studies are warranted to evaluate the effects of WBV on postural control in an elderly population.</p

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

Biology and conservation of freshwater bivalves : past, present and future perspectives

Freshwater bivalves have been highly threatened by human activities, and recently their global decline has been causing conservational and social concern. In this paper, we review the most important research events in freshwater bivalve biology calling attention to the main scientific achievements. A great bias exists in the research effort, with much more information available for bivalve species belonging to the Unionida in comparison to other groups. The same is true for the origin of these studies, since the publishing pattern does not always correspond to the hotspots of biodiversity but is concentrated in the northern hemisphere mainly in North America, Europe and Russia, with regions such as Africa and Southeast Asia being quite understudied. We also summarize information about past, present and future perspectives concerning the most important research topics that include taxonomy, systematics, anatomy, physiology, ecology and conservation of freshwater bivalves. Finally, we introduce the articles published in this Hydrobiologia special issue related with the International Meeting on Biology and Conservation of Freshwater Bivalves held in 2012 in Braganc¸a, Portugal.We would like to express our gratitude to our sponsors and institutions, especially to the Polytechnic Institute of Braganca for all the logistic support. We acknowledge all keynote speakers, authors, session chairpersons and especially to all attendees whose contributions were fundamental for the success of this meeting. We would also like to thank all referees of this special issue and to Koen Martens, Editor-in-Chief of Hydrobiologia, for all the valuable comments and suggestions. The chronogram was built with the help of the expert opinion of fellow colleagues Rafael Araujo, Arthur Bogan, Kevin Cummings, Dan Graf, Wendell Haag, Karl-Otto Nagel and David Strayer to whom we are very grateful. The authors acknowledge the support provided by Portuguese Foundation for Science and Technology (FCT) and COMPETE funds-projects CONBI (Contract: PTDC/AAC-AMB/117688/2010) and ECO-IAS (Contract: PTDC/AAC-AMB/116685/2010), and by the European Regional Development Fund (ERDF) through the COMPETE, under the project "PEst-C/MAR/LA0015/2011"