Longitudinal assessment of cyst-like lesions of the knee and their relation to radiographic osteoarthritis and MRI-detected effusion and synovitis in patients with knee pain

Introduction\ud The purpose of the present study was to determine the prevalence of cystic lesions and cyst-like bursitides in subjects with frequent knee pain and to assess their relation to radiographic osteoarthritis (OA) severity; to describe bilaterality and size fluctuation of the lesions over 6 months; and to assess relations between the prevalence of synovium-lined lesions communicating with the joint capsule and severity of magnetic resonance imaging (MRI)-detected effusion and synovitis.\ud \ud Methods\ud One hundred and sixty-three subjects (total 319 knees) aged 35 to 65 with chronic, frequent knee pain were included. Imaging with 3 Tesla MRI was performed at baseline and 6-month follow-up with the same protocols as those used in the Osteoarthritis Initiative. Severity of radiographic OA was assessed using the Kellgren-Lawrence grade (0 to 4). Severity of effusion and synovitis was graded 0 to 3 based on the Whole Organ Magnetic Resonance Imaging Score system. The associations of cysts and cyst-like bursitides and severity of radiographic OA, MRI-detected effusion and synovitis were analyzed using logistic regression controlling for clustering by person. The Wilcoxon signed-rank test was used to determine whether there was a significant change in the size of lesions between baseline and follow-up.\ud \ud Results\ud At least one lesion (any type) was present in 222 (70%) knees. The most prevalent lesions were popliteal cysts (40%, 128/319), followed by subgastrocnemius bursitis (15%, 49/319) and proximal tibiofibular joint cysts (8%, 26/319). Bilateral lesions were seen in 49% of the subjects. Only popliteal cysts and subgastrocnemius bursitis showed a significant change in size (P < 0.001). No trend was observed between prevalence of any of the cyst-like lesions analyzed and the increasing radiographic OA severity. Increasing prevalence of subgastrocnemius bursitis was associated with increasing severity of effusion (P = 0.0072) and synovitis (P = 0.0033).\ud \ud Conclusions\ud None of the cyst-like lesions analyzed seems to be a marker of radiographic OA severity in knees with chronic frequent pain. Subgastrocnemius bursitis may be used as a marker of effusion/synovitis severity. Bilateral cyst-like lesions are relatively commonly observed in people with chronic knee pain

Environmental Effects in Clusters: Modified Far-Infrared--Radio Relations within Virgo Cluster Galaxies

(abridged) We present a study on the effects of the intracluster medium (ICM) on the interstellar medium (ISM) of 10 Virgo cluster spiral galaxies using {\it Spitzer} far-infrared (FIR) and VLA radio continuum imaging. Relying on the FIR-radio correlation within normal galaxies, we use our infrared data to create model radio maps which we compare to the observed radio images. For 6 of our sample galaxies we find regions along their outer edges that are highly deficient in the radio compared with our models. We believe these observations are the signatures of ICM ram pressure. For NGC 4522 we find the radio deficit region to lie just exterior to a region of high radio polarization and flat radio spectral index, although the total 20 cm radio continuum in this region does not appear strongly enhanced. These characteristics seem consistent for other galaxies with radio polarization data in the literature. The strength of the radio deficit is inversely correlated with the time since peak pressure as inferred from stellar population studies and gas stripping simulations, suggesting the strength of the radio deficit is good indicator of the strength of the current ram pressure. We also find that galaxies having {\it local} radio {\it deficits} appear to have {\it enhanced global} radio fluxes. Our preferred physical picture is that the observed radio deficit regions arise from the ICM wind sweeping away cosmic-ray (CR) electrons and the associated magnetic field, thereby creating synchrotron tails as observed for some of our galaxies. We propose that CR particles are also re-accelerated by ICM-driven shocklets behind the observed radio deficit regions which in turn enhances the remaining radio disk brightness.Comment: 19 pages, 10 figures; Astrophysical Journa

Genome-wide screening of mouse knockouts reveals novel genes required for normal integumentary and oculocutaneous structure and function.

Oculocutaneous syndromes are often due to mutations in single genes. In some cases, mouse models for these diseases exist in spontaneously occurring mutations, or in mice resulting from forward mutatagenesis screens. Here we present novel genes that may be causative for oculocutaneous disease in humans, discovered as part of a genome-wide screen of knockout-mice in a targeted single-gene deletion project. The International Mouse Phenotyping Consortium (IMPC) database (data release 10.0) was interrogated for all mouse strains with integument abnormalities, which were then cross-referenced individually to identify knockouts with concomitant ocular abnormalities attributed to the same targeted gene deletion. The search yielded 307 knockout strains from unique genes with integument abnormalities, 226 of which have not been previously associated with oculocutaneous conditions. Of the 307 knockout strains with integument abnormalities, 52 were determined to have ocular changes attributed to the targeted deletion, 35 of which represent novel oculocutaneous genes. Some examples of various integument abnormalities are shown, as well as two examples of knockout strains with oculocutaneous phenotypes. Each of the novel genes provided here are potentially relevant to the pathophysiology of human integumentary, or oculocutaneous conditions, such as albinism, phakomatoses, or other multi-system syndromes. The novel genes reported here may implicate molecular pathways relevant to these human diseases and may contribute to the discovery of novel therapeutic targets

Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?

BACKGROUND: Early identification of patients with drug-resistant tuberculosis (DR-TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss. METHODS: A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB. RESULTS: Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9). CONCLUSIONS: Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority

Semiquantitative assessment of subchondral bone marrow edema-like lesions and subchondral cysts of the knee at 3T MRI: A comparison between intermediate-weighted fat-suppressed spin echo and Dual Echo Steady State sequences

Background\ud Choice of appropriate MR pulse sequence is important for any research studies using imaging-derived data. The aim of this study was to compare semiquantitative assessment of subchondral bone marrow edema-like lesions and subchondral cysts using intermediate-weighted (IW) fat-suppressed (fs) spin echo and Dual Echo Steady State (DESS) sequences on 3 T MRI.\ud \ud Methods\ud Included were 201 subjects aged 35-65 with frequent knee pain. 3T MRI was performed with the same sequence protocol as in the Osteoarthritis Initiative (OAI). In a primary reading subchondral bone marrow edema-like lesions were assessed according to the WORMS system. Two hundred subregions with such lesions were randomly chosen. The extent of subchondral bone marrow edema-like lesions was re-evaluated separately using sagittal IW fs and DESS sequences according to WORMS. Lesion size and confidence of the differentiation between subchondral bone marrow edema-like lesions and subchondral cysts located within or adjacent to them was rated from 0 to 3. Wilcoxon signed-rank tests and chi-square statistics were used to examine differences between the two sequences.\ud \ud Results\ud Of 200 subchondral bone marrow edema-like lesions detected by IW fs sequence, 93 lesions (46.5%) were not depicted by the DESS sequence. The IW fs sequence depicted subchondral bone marrow edema-like lesions to a larger extent than DESS (p < 0.0001), and the opposite was true for subchondral cysts. Confidence scores for differentiation of the two types of lesions were not significantly different between the two sequences.\ud \ud Conclusions\ud In direct comparison the IW fs sequence depicts more subchondral bone marrow edema-like lesions and better demonstrate the extent of their maximum size. The DESS sequence helps in the differentiation of subchondral bone marrow edema-like lesions and subchondral cysts. The IW fs sequence should be used for determination of lesion extent whenever the size of subchondral bone marrow edema-like lesions is the focus of attention

Pitch strength of normal and dysphonic voices

Two sounds with the same pitch may vary from each other based on saliency of their pitch sensation. This perceptual attribute is called “pitch strength.” The study of voice pitch strength may be important in quantifying of normal and pathological qualities. The present study investigated how pitch strength varies across normal and dysphonic voices. A set of voices (vowel /a/) selected from the Kay Elemetrics Disordered Voice Database served as the stimuli. These stimuli demonstrated a wide range of voice quality. Ten listeners judged the pitch strength of these stimuli in an anchored magnitude estimation task. On a given trial, listeners heard three different stimuli. The first stimulus represented very low pitch strength (wide-band noise), the second stimulus consisted of the target voice and the third stimulus represented very high pitch strength (pure tone). Listeners estimated pitch strength of the target voice by positioning a continuous slider labeled with values between 0 and 1, reflecting the two anchor stimuli. Results revealed that listeners can judge pitch strength reliably in dysphonic voices. Moderate to high correlations with perceptual judgments of voice quality suggest that pitch strength may contribute to voice quality judgments

Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants

BACKGROUND During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation. METHODS Kidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24h after birth. Using image analysis, nephrogenic zone width, the number of glomerular generations, renal corpuscle cross-sectional area and the cellular composition of glomeruli were examined. Kidneys from female and male infants were analysed separately. FINDINGS The number of glomerular generations formed within the fetal kidneys was directly proportional to gestational age, body weight and kidney weight, with variability between individuals in the ultimate number of generations (8 to 12) and in the timing of the cessation of nephrogenesis (still ongoing at 37weeks gestation in one infant). There was a slight but significant (r2=0.30, P=0.001) increase in renal corpuscle cross-sectional area from mid gestation to term in females, but this was not evident in males. The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation. INTERPRETATION These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.This study was supported by funding from the National Health and Medical Research Council (NHMRC) (1011136) of Australia and National Institutes of Health (NIH) USA grant 3U01DK094526-04S1 (PI A P McMahon). Author Danica Ryan was the recipient of the Biomedicine Discovery Scholarship from Monash University and author Megan R. Sutherland was supported by a NHMRC CJ Martin Fellowship

The velocity function in the local environment from LCDM and LWDM constrained simulations

Using constrained simulations of the local Universe for generic cold dark matter and for 1keV warm dark matter, we investigate the difference in the abundance of dark matter halos in the local environment. We find that the mass function within 20 Mpc/h of the Local Group is ~2 times larger than the universal mass function in the 10^9-10^13 M_odot/h mass range. Imposing the field of view of the on-going HI blind survey ALFALFA in our simulations, we predict that the velocity function in the Virgo-direction region exceeds the universal velocity function by a factor of 3. Furthermore, employing a scheme to translate the halo velocity function into a galaxy velocity function, we compare the simulation results with a sample of galaxies from the early catalog release of ALFALFA. We find that our simulations are able to reproduce the velocity function in the 80-300 km/s velocity range, having a value ~10 times larger than the universal velocity function in the Virgo-direction region. In the low velocity regime, 35-80 km/s, the warm dark matter simulation reproduces the observed flattening of the velocity function. On the contrary, the simulation with cold dark matter predicts a steep rise in the velocity function towards lower velocities; for V_max=35 km/s, it forecasts ~10 times more sources than the ones observed. If confirmed by the complete ALFALFA survey, our results indicate a potential problem for the cold dark matter paradigm or for the conventional assumptions about energetic feedback in dwarf galaxies.Comment: 24 pages, 14 figures, 1 table, accepted for publication in Ap

Comparative Field Evaluation of Combinations of Long-Lasting Insecticide Treated Nets and Indoor Residual Spraying, Relative to Either Method Alone, for Malaria Prevention in an Area where the main Vector is Anopheles Arabiensis.

Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used together in the same households to improve malaria control despite inconsistent evidence on whether such combinations actually offer better protection than nets alone or IRS alone. Comparative tests were conducted using experimental huts fitted with LLINs, untreated nets, IRS plus untreated nets, or combinations of LLINs and IRS, in an area where Anopheles arabiensis is the predominant malaria vector species. Three LLIN types, Olyset®, PermaNet 2.0® and Icon Life® nets and three IRS treatments, pirimiphos-methyl, DDT, and lambda cyhalothrin, were used singly or in combinations. We compared, number of mosquitoes entering huts, proportion and number killed, proportions prevented from blood-feeding, time when mosquitoes exited the huts, and proportions caught exiting. The tests were done for four months in dry season and another six months in wet season, each time using new intact nets. All the net types, used with or without IRS, prevented >99% of indoor mosquito bites. Adding PermaNet 2.0® and Icon Life®, but not Olyset® nets into huts with any IRS increased mortality of malaria vectors relative to IRS alone. However, of all IRS treatments, only pirimiphos-methyl significantly increased vector mortality relative to LLINs alone, though this increase was modest. Overall, median mortality of An. arabiensis caught in huts with any of the treatments did not exceed 29%. No treatment reduced entry of the vectors into huts, except for marginal reductions due to PermaNet 2.0® nets and DDT. More than 95% of all mosquitoes were caught in exit traps rather than inside huts. Where the main malaria vector is An. arabiensis, adding IRS into houses with intact pyrethroid LLINs does not enhance house-hold level protection except where the IRS employs non-pyrethroid insecticides such as pirimiphos-methyl, which can confer modest enhancements. In contrast, adding intact bednets onto IRS enhances protection by preventing mosquito blood-feeding (even if the nets are non-insecticidal) and by slightly increasing mosquito mortality (in case of LLINs). The primary mode of action of intact LLINs against An. arabiensis is clearly bite prevention rather than insecticidal activity. Therefore, where resources are limited, priority should be to ensure that everyone at risk consistently uses LLINs and that the nets are regularly replaced before being excessively torn. Measures that maximize bite prevention (e.g. proper net sizes to effectively cover sleeping spaces, stronger net fibres that resist tears and burns and net use practices that preserve net longevity), should be emphasized

Characterization of five members of the actin gene family in the sea urchin

Hybridization of an actin cDNA clone (pSA38) to restriction enzyme digests of Strongylocentrotus purpuratus DNA indicates that the sea urchin genome contains at least five different actin genes. A sea urchin genomic clone library was screened for recombinants which hydridize to pSA38 and four genomic clones were isolated. Restriction maps were generated which indicate that three of these recombinants contain different actin genes, and that the fourth may be an allele to one of these. The restriction maps suggest that one clone contains two linked actin genes. This fact, which was confirmed by heteroduplex analysis, indicates that the actin gene family may be clustered. The linked genes are oriented in the same direction and spaced about 8.0 kilobases apart. In heteroduplexes between genomic clones two intervening sequences were seen. Significant homology is confined to the actin coding region and does not include any flanking sequence. Southern blot analysis reveals that repetitive DNA sequences are found in the region of the actin genes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24164/1/0000422.pd