Temporal and Spatial Expression of Tissue Inhibitors of Metalloproteinases 1 and 2 (TIMP-1 and -2) in the Bovine Corpus Luteum

The matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), may mediate the dramatic structural and functional changes in the corpus luteum (CL) over the course of its life span. In addition to regulating MMP activity, TIMPs are also involved in a variety of cellular processes, including cell proliferation and steroidogenesis. In a series of initial studies, we determined that matrix metalloproteinase inhibitory activity was present in protein extracts from early (4 days old, estrus = day 0), mid (10–12 days old) and late (16 days old) CL (n = 3 for each stage). Reverse zymography revealed four metalloproteinase inhibitory protein bands with relative molecular masses that are consistent with those reported for TIMP-1 to -4. In order to gain a better understanding of TIMPs and their role in luteal function, we further characterized this inhibitory activity with a particular focus on the temporal and spatial expression of TIMP-1 and TIMP-2 in the bovine CL. Northern blotting revealed that the TIMP-1 transcript (0.9 kb) was expressed at a higher (p < 0.05) level in early and mid cycle CL than in the late stage. In contrast, two TIMP-2 mRNA species, one major 1 kb species and one minor 3.5 kb species, were significantly (p < 0.05) increased in the mid and late cycle CL than in the early. Western blotting analyses demonstrated no differences in TIMP-1 (29 kDa) protein levels between early and mid stages, while its levels decreased (p < 0.05) from the mid to late stage CL. Conversely, TIMP-2 (22 kDa) protein was detected at a low level in the early CL, but significantly (p < 0.05) increased in the mid and late stages. Immunohistochemistry revealed that both TIMP-1 and -2 were localized to large luteal cells from all three ages of CL. TIMP-1 was also localized in capillary smooth muscle cells, while TIMP-2 was restricted to the endothelial cells in the capillary compartment. In conclusion, the different temporal expression patterns of TIMP-1 and TIMP-2 suggest that TIMP-1 may be important for luteal formation and development, while TIMP-2 may play significant roles during luteal development and maintenance. Furthermore, the distinct localization of these two inhibitors in the vascular compartment indicates that they may serve diverse physiological functions during different stages of luteal angiogenesis

Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial.

&lt;b&gt;Objective&lt;/b&gt;: It was hypothesized that the use of exercise limits prevents symptom increases and worsening of their health status following a walking exercise in people with Chronic Fatigue Syndrome (CFS). &lt;b&gt;Design&lt;/b&gt;: An uncontrolled clinical trial (semi-experimental design). &lt;b&gt;Setting&lt;/b&gt;: Outpatient clinic of a university department. &lt;b&gt;Subjects&lt;/b&gt;: 24 patients with CFS. &lt;b&gt;Interventions&lt;/b&gt;: Subjects undertook a walking test with the two concurrent exercise limits. Each subject walked at an &lt;i&gt;intensity&lt;/i&gt; where the maximum heart rate was determined by heart rate corresponding to the respiratory exchange ratio =1.0 derived from a previous sub-maximal exercise test and for a duration calculated from how long each patient felt they were able to walk. &lt;b&gt;Main outcome measures&lt;/b&gt;: The Short Form 36 Health Survey or SF-36, the CFS Symptom List, and the CFS-Activities and Participation Questionnaire were filled in prior to, immediately and 24 hours post-exercise. &lt;b&gt;Results&lt;/b&gt;: The fatigue increase observed immediately post-exercise (p=0.006) returned to pre-exercise levels 24 hours post-exercise. The increase in pain observed immediately post-exercise was retained at 24 hours post-exercise (p=0.03). Fourteen of 24 subjects experienced a clinically meaningful change in bodily pain (change of SF-36 bodily pain score ³10). Six of 24 participants indicated that the exercise bout had slightly worsened their health status, and 2 of 24 had a clinically meaningful decrease in vitality (change of SF-36 vitality score ³20). There was no change in activity limitations/participation restrictions. &lt;b&gt;Conclusion&lt;/b&gt;: It was shown that the use of exercise limits (limiting both the intensity and duration of exercise) prevents important health status changes following a walking exercise in people with CFS, but was unable to prevent short-term symptom increases

Absorbable versus silk sutures for surgical treatment of trachomatous trichiasis in Ethiopia: a randomised controlled trial.

BACKGROUND: Trachoma causes blindness through an anatomical abnormality called trichiasis (lashes touching the eye). Trichiasis can recur after corrective surgery. We tested the hypothesis that using absorbable sutures instead of silk sutures might reduce the risk of recurrent disease among patients with major trichiasis in a randomised trial. METHODS AND FINDINGS: 1,300 individuals with major trichiasis from rural villages in the Amhara Region of Ethiopia were recruited and assigned (1:1) by computer-generated randomisation sequence to receive trichiasis surgery using either an absorbable suture (polyglactin-910) or silk sutures (removed at 7-10 days) in an otherwise identical surgical technique. Participants were examined every 6 months for 2 years by clinicians masked to allocation. The primary outcome measure was recurrent trichiasis (≥one lash touching the eye) at 1 year. There was no difference in prevalence of recurrent trichiasis at 1 year (114 [18.2%] in the absorbable suture group versus 120 [19.7%] in the silk suture group; odds ratio = 0.90, 95% CI 0.68-1.20). The two groups also did not differ in terms of corneal opacification, visual acuity, conjunctival inflammation, and surgical complications. CONCLUSIONS: There was no evidence that use of absorbable polyglactin-910 sutures was associated with a lower prevalence of trichiasis recurrence at 1 year postsurgery than silk sutures. However, from a programmatic perspective, polyglactin-910 offers the major advantage that patients do not have to be seen soon after surgery for suture removal. The postoperative review after surgery using absorbable polyglactin-910 sutures can be delayed for 3-6 months, which might allow us to better determine whether a patient needs additional surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT00522860

Interactions between downslope flows and a developing cold-air pool

A numerical model has been used to characterize the development of a region of enhanced cooling in an alpine valley with a width of order (Formula presented.) km, under decoupled stable conditions. The region of enhanced cooling develops largely as a region of relatively dry air which partitions the valley atmosphere dynamics into two volumes, with airflow partially trapped within the valley by a developing elevated inversion. Complex interactions between the region of enhanced cooling and the downslope flows are quantified. The cooling within the region of enhanced cooling and the elevated inversion is almost equally partitioned between radiative and dynamic effects. By the end of the simulation, the different valley atmospheric regions approach a state of thermal equilibrium with one another, though this cannot be said of the valley atmosphere and its external environment.Peer reviewe

How liquid are banks : some evidence from the United Kingdom

This paper uses quantitative balance sheet liquidity analysis, based upon modified versions of the BCBS 1 and Moody’s 2 models, to provide indicators which would alarm the UK banks’ short and long-term liquidity positions respectively. These information will also underpin other research related liquidity risk to banks’ lending and performance. Our framework accurately reflect UK banks’ liquidity positions under both normal and stress scenarios based on the consistent accounting information under IFRS. It has significant contribution on Basel III liquidity ratios calculation. The study also presents fundamental financial information to facilitate analysis of banks’ business models and funding strategies. Using data for the period 2005-2010, we provide evidence that there have been variable liquidity strains across the UK banks in our sample. The estimated results show that Barclays Bank was the only bank to maintain a healthy short-term liquidity position throughout the sample period; while HSBC remained liquid in the short term, in both normal and stress conditions, except in 2008 and 2010. RBS, meanwhile, maintained healthy long-term liquidity positions from 2008 after receiving government injections of capital. And Santander UK was also able to post healthy long-term liquidity positions, except in 2009. However, the other four banks, the Bank of Scotland, Lloyds TSB, Natwest, and Standard Chartered, proved illiquid, on both a short-term and long-term basis, throughout the six-year period, with Natwest being by far the worst performer

Defining Seropositivity Thresholds for Use in Trachoma Elimination Studies.

BACKGROUND: Efforts are underway to eliminate trachoma as a public health problem by 2020. Programmatic guidelines are based on clinical signs that correlate poorly with Chlamydia trachomatis (Ct) infection in post-treatment and low-endemicity settings. Age-specific seroprevalence of anti Ct Pgp3 antibodies has been proposed as an alternative indicator of the need for intervention. To standardise the use of these tools, it is necessary to develop an analytical approach that performs reproducibly both within and between studies. METHODOLOGY: Dried blood spots were collected in 2014 from children aged 1-9 years in Laos (n = 952) and Uganda (n = 2700) and from people aged 1-90 years in The Gambia (n = 1868). Anti-Pgp3 antibodies were detected by ELISA. A number of visual and statistical analytical approaches for defining serological status were compared. PRINCIPAL FINDINGS: Seroprevalence was estimated at 11.3% (Laos), 13.4% (Uganda) and 29.3% (The Gambia) by visual inspection of the inflection point. The expectation-maximisation algorithm estimated seroprevalence at 10.4% (Laos), 24.3% (Uganda) and 29.3% (The Gambia). Finite mixture model estimates were 15.6% (Laos), 17.1% (Uganda) and 26.2% (The Gambia). Receiver operating characteristic (ROC) curve analysis using a threshold calibrated against external reference specimens estimated the seroprevalence at 6.7% (Laos), 6.8% (Uganda) and 20.9% (The Gambia) when the threshold was set to optimise Youden's J index. The ROC curve analysis was found to estimate seroprevalence at lower levels than estimates based on thresholds established using internal reference data. Thresholds defined using internal reference threshold methods did not vary substantially between population samples. CONCLUSIONS: Internally calibrated approaches to threshold specification are reproducible and consistent and thus have advantages over methods that require external calibrators. We propose that future serological analyses in trachoma use a finite mixture model or expectation-maximisation algorithm as a means of setting the threshold for ELISA data. This will facilitate standardisation and harmonisation between studies and eliminate the need to establish and maintain a global calibration standard

Anthropometric Comparison Of Cephalic Indices Between The Urhobo And Itsekiri Ethnic Groups Of Nigeria

Cephalic index is an important parameter for classifying populations. In the present study, one thousand students with age ranging from 18 to 25 years of Urhobo and Itsekiri origin from rural and urban areas of Delta State of Nigeria were measured. The study was aimed at determining possible similarities and differences in the cephalic indices of the Urhobos and Itsekiris. The subjects were measured for head length and head breadth and cephalic index was worked out by dividing the head breadth by head length and multiplying by 100. Five hundred subjects comprising 250 males and 250 females for each tribe were measured. The cephalic indices for both groups were calculated and the result analyzed using z-test. On the average, the mean cephalic index in the two groups was >80 which puts them in the brachycephalic population. The z-test analysis indicated that there was significant difference between the Itsekiri males and Urhobo males and between the Itsekiri males and Urhobo females-However there was no significant difference between the two groups in general (P>0.05). The result of this study will be of importance in forensic medicine, anthropology and in genetics

Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci

African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda) and Southern (Malawi) Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics