Aqueous tear assessment in dogs: Impact of cephalic conformation, inter‐test correlations, and test‐retest repeatability

Objective - To characterize diagnostic findings, test‐retest repeatability, and correlations among lacrimal tests in dogs of diverse cephalic conformations. Animal studied - Fifty healthy dogs (25 brachycephalic, 25 nonbrachycephalic). Procedures - A series of diagnostics were performed in each dog, allowing for a 10‐minute interval between tests and repeating each test 24 hours later under similar conditions: corneal tactile sensation (CTS), strip meniscometry test (SMT), phenol red thread test (PRTT), endodontic absorbent paper point tear test (EAPPTT), Schirmer tear test‐1 without (STT‐1) or with nasolacrimal stimulation (NL‐STT1), and Schirmer tear test‐2 (STT‐2). Results - Mean ± SD test values were lower in brachycephalic vs. nonbrachycephalic dogs (except for SMT; 7.4 ± 2.0 mm/5 seconds vs 7.3 ± 2.4 mm/5 seconds), with statistically significant differences noted for CTS (1.8 ± 0.5 cm vs 3.4 ± 0.8 cm), PRTT (37.2 ± 4.0 mm/15 seconds vs 41.1 ± 5.5 mm/15 seconds), STT‐1 (20.1 ± 3.4 mm/min vs 23.3 ± 5.7 mm/min), STT‐2 (13.0 ± 3.4 mm/min vs 16.9 ± 3.9 mm/min), and NL‐STT1 (23.2 ± 3.6 mm/min vs 27.1 ± 5.4 mm/min), and nonsignificant differences for EAPPTT (16.6 ± 2.7 mm/15 seconds vs 17.5 ± 2.9 mm/15 seconds). Nasolacrimal stimulation increased STT‐1 values by 18% on average. Correlations among tests were generally weak to moderate (r \u3c .70) except for a strong correlation between STT‐1 and NL‐STT1 (r = .83, P \u3c .001). Test reliability was good although test‐retest repeatability was generally poor to moderate, as depicted by low intraclass correlation coefficients (ICC ≤ 0.75) and wide 95% limits of agreement, except for CTS (ICC = 0.91). Conclusions - Corneal sensitivity and aqueous tear secretion are lower in brachycephalic dogs. A comprehensive assessment of the ocular surface requires the combination of several diagnostic tests. The nasolacrimal reflex may provide a useful diagnostic and therapeutic tool in dogs

Keratin 6 is not essential for mammary gland development

INTRODUCTION: Keratin 6 (K6) has previously been identified as a marker of early mammary gland development and has also been proposed to be a marker of mammary gland progenitor cells. However, the function of K6 in the mammary gland was not known, so we examined the expression pattern of the protein during both embryonic and postnatal mammary development, as well as the mammary gland phenotype of mice that were null for both K6a and K6b isoforms. METHOD: Immunostaining was performed to determine the expression pattern of K6a throughout mammary gland development, from the embryonic mammary bud to lactation. Double immunofluorescence was used to co-localize K6 with known markers of mammary gland development. Wild-type and K6ab-null mammary tissues were transplanted into the cleared fat pads of nude mice and the outgrowths were analyzed for morphology by whole-mount staining and for markers of mammary epithelium by immunostaining. Finally, progesterone receptor (PR) and bromodeoxyuridine co-localization was quantified by double immunofluorescence in wild-type and K6ab-null mammary outgrowths. RESULTS: Here we report that K6 is expressed earlier than described previously, by embryonic day 16.5. K6a is the predominant isoform expressed in the mammary gland, localized in the body cells and luminal epithelial cells but not in the cap cells or myoepithelial cells. Co-localization studies showed that most K6a-positive cells express steroid receptors but do not proliferate. When both the K6a and K6b genes are deleted, mammary gland development appears normal, with similar expression of most molecular markers examined in both the pubertal gland and the mature gland. Loss of K6a and K6b, however, leads to an increase in the number of steroid-receptor-positive cells, and increased co-localization of steroid receptor expression and proliferation was observed. CONCLUSION: Although K6a was not essential for mammary gland development, loss of both K6a and K6b resulted in an increase in PR-positive mammary epithelial cells and decreased proliferation after exposure to steroid hormones. There was also increased co-localization of PR and bromodeoxyuridine, suggesting alterations in patterning events important for normal lobuloalveolar development

Ficaria verna Huds. extracts and their β-cyclodextrin supramolecular systems

<p>Abstract</p> <p>Background</p> <p>Obtaining new pharmaceutical materials with enhanced properties by using natural compounds and environment-friendly methods is a continuous goal for scientists. <it>Ficaria verna </it>Huds. is a widespread perennial plant with applications in the treat of haemorrhoids and to cure piles; it has also anti-inflammatory, astringent, and antibiotic properties. The goal of the present study is the obtaining and characterization of new <it>F. verna </it>extract/β-cyclodextrin complexes by using only natural compounds, solvents, and environment-friendly methods in order to increase the quality and acceptability versus toxicity indicator. Thus, the flavonoid content (as quercetin) of <it>Ficaria verna </it>Huds. flowers and leaves from the West side of Romania was determined and correlated with their antioxidant activity. Further, the possibility of obtaining β-cyclodextrin supramolecular systems was studied.</p> <p>Results</p> <p><it>F. verna </it>flowers and leaves extracts were obtained by semi-continuous solid-liquid extraction. The raw concentrated extract was spectrophotometrically analyzed in order to quantify the flavonoids from plant parts and to evaluate the antioxidant activity of these extracts. The <it>F. verna </it>extracts were used for obtaining β-cyclodextrin complexes; these were analyzed by scanning electron microscopy and Karl Fischer water titration; spectrophotometry was used in order to quantifying the flavonoids and evaluates the antioxidant activity. A higher concentration of flavonoids of 0.5% was determined in complexes obtained by crystallisation method, while only a half of this value was calculated for kneading method. The antioxidant activity of these complexes was correlated with the flavonoid content and this parameter reveals possible controlled release properties.</p> <p>Conclusions</p> <p>The flavonoid content of <it>F. verna </it>Huds. from the West side of Romania (Banat county) is approximately the same in flowers and leaves, being situated at a medium value among other studies. β-Cyclodextrin complexes of <it>F. verna </it>extracts are obtained with lower yields by crystallisation than kneading methods, but the flavonoids (as quercetin) are better encapsulated in the first case most probably due to the possibility to attain the <it>host</it>-<it>guest </it>equilibrium in the slower crystallisation process. <it>F. verna </it>extracts and their β-cyclodextrin complexes have antioxidant activity even at very low concentrations and could be used in proper and valuable pharmaceutical formulations with enhanced bioactivity.</p

Extreme rainfall events alter the trophic structure in bromeliad tanks across the Neotropics

Changes in global and regional precipitation regimes are among the most pervasive components of climate change. Intensification of rainfall cycles, ranging from frequent downpours to severe droughts, could cause widespread, but largely unknown, alterations to trophic structure and ecosystem function. We conducted multi-site coordinated experiments to show how variation in the quantity and evenness of rainfall modulates trophic structure in 210 natural freshwater microcosms (tank bromeliads) across Central and South America (18°N to 29°S). The biomass of smaller organisms (detritivores) was higher under more stable hydrological conditions. Conversely, the biomass of predators was highest when rainfall was uneven, resulting in top-heavy biomass pyramids. These results illustrate how extremes of precipitation, resulting in localized droughts or flooding, can erode the base of freshwater food webs, with negative implications for the stability of trophic dynamics

Social inequalities in self-rated health by age: Cross-sectional study of 22 457 middle-aged men and women

<p>Abstract</p> <p>Background</p> <p>We investigate the association between occupational social class and self-rated health (SRH) at different ages in men and women.</p> <p>Methods</p> <p>Cross sectional population study of 22 457 men and women aged 39–79 years living in the general community in Norfolk, United Kingdom, recruited using general practice age-sex registers in 1993–1997. The relationship between self-rated health and social class was examined using logistic regression, with a poor or moderate rating as the outcome.</p> <p>Results</p> <p>The prevalence of poor or moderate (lower) self-rated health increased with increasing age in both men and women. There was a strong social class gradient: in manual classes, men and women under 50 years of age had a prevalence of lower self-rated health similar to that seen in men and women in non-manual social classes over 70 years old. Even after adjustment for age, educational status, and lifestyle factors (body mass index (BMI), smoking, physical activity and alcohol consumption) there was still strong evidence of a social gradient in self-rated health, with unskilled men and women approximately twice as likely to report lower self-rated health as professionals (OR_men= 2.44 (95%CI 1.69, 3.50); OR_women= 1.97 (95%CI 1.45, 2.68).</p> <p>Conclusion</p> <p>There was a strong gradient of decreased SRH with age in both men and women. We found a strong cross-sectional association between SRH and social class, which was independent of education and major health related behaviors. The social class differential in SRH was similar with age. Prospective studies to confirm this association should explore social and emotional as well as physical pathways to inequalities in self reported health.</p

Is the health of people living in rural areas different from those in cities? Evidence from routine data linked with the Scottish Health Survey

<p>Abstract</p> <p>Background</p> <p>To examine the association between rurality and health in Scotland, after adjusting for differences in individual and practice characteristics.</p> <p>Methods</p> <p>Design: Mortality and hospital record data linked to two cross sectional health surveys. Setting: Respondents in the community-based 1995 and 1998 Scottish Health Survey who consented to record-linkage follow-up. Main outcome measures: Hypertension, all-cause premature mortality, total hospital stays and admissions due to coronary heart disease (CHD).</p> <p>Results</p> <p>Older age and lower social class were strongly associated with an increased risk of each of the four health outcomes measured. After adjustment for individual and practice characteristics, no consistent pattern of better or poorer health in people living in rural areas was found, compared to primary cities. However, individuals living in remote small towns had a lower risk of a hospital admission for CHD and those in very remote rural had lower mortality, both compared with those living in primary cities.</p> <p>Conclusion</p> <p>This study has shown how linked data can be used to explore the possible influence of area of residence on health. We were unable to find a consistent pattern that people living in rural areas have materially different health to that of those living in primary cities. Instead, we found stronger relationships between compositional determinants (age, gender and socio-economic status) and health than contextual factors (including rurality).</p

Chemical Magnetoreception: Bird Cryptochrome 1a Is Excited by Blue Light and Forms Long-Lived Radical-Pairs

Cryptochromes (Cry) have been suggested to form the basis of light-dependent magnetic compass orientation in birds. However, to function as magnetic compass sensors, the cryptochromes of migratory birds must possess a number of key biophysical characteristics. Most importantly, absorption of blue light must produce radical pairs with lifetimes longer than about a microsecond. Cryptochrome 1a (gwCry1a) and the photolyase-homology-region of Cry1 (gwCry1-PHR) from the migratory garden warbler were recombinantly expressed and purified from a baculovirus/Sf9 cell expression system. Transient absorption measurements show that these flavoproteins are indeed excited by light in the blue spectral range leading to the formation of radicals with millisecond lifetimes. These biophysical characteristics suggest that gwCry1a is ideally suited as a primary light-mediated, radical-pair-based magnetic compass receptor

Understanding the context of balanced scorecard implementation: a hospital-based case study in pakistan

Background: As a response to a changing operating environment, healthcare administrators are implementing modern management tools in their organizations. The balanced scorecard (BSC) is considered a viable tool in high-income countries to improve hospital performance. The BSC has not been applied to hospital settings in low-income countries nor has the context for implementation been examined. This study explored contextual perspectives in relation to BSC implementation in a Pakistani hospital. Methods: Four clinical units of this hospital were involved in the BSC implementation based on their willingness to participate. Implementation included sensitization of units towards the BSC, developing specialty specific BSCs and reporting of performance based on the BSC during administrative meetings. Pettigrew and Whipp\u27s context (why), process (how) and content (what) framework of strategic change was used to guide data collection and analysis. Data collection methods included quantitative tools (a validated culture assessment questionnaire) and qualitative approaches including key informant interviews and participant observation.Results: Method triangulation provided common and contrasting results between the four units. A participatory culture, supportive leadership, financial and non-financial incentives, the presentation of clear direction by integrating support for the BSC in policies, resources, and routine activities emerged as desirable attributes for BSC implementation. The two units that lagged behind were more involved in direct inpatient care and carried a considerable clinical workload. Role clarification and consensus about the purpose and benefits of the BSC were noted as key strategies for overcoming implementation challenges in two clinical units that were relatively ahead in BSC implementation. It was noted that, rather than seeking to replace existing information systems, initiatives such as the BSC could be readily adopted if they are built on existing infrastructures and data networks. Conclusion: Variable levels of the BSC implementation were observed in this study. Those intending to apply the BSC in other hospital settings need to ensure a participatory culture, clear institutional mandate, appropriate leadership support, proper reward and recognition system, and sensitization to BSC benefits

Phenotypic and Functional Characterization of Human Mammary Stem/Progenitor Cells in Long Term Culture

Background: Cancer stem cells exhibit close resemblance to normal stem cells in phenotype as well as function. Hence, studying normal stem cell behavior is important in understanding cancer pathogenesis. It has recently been shown that human breast stem cells can be enriched in suspension cultures as mammospheres. However, little is known about the behavior of these cells in long-term cultures. Since extensive self-renewal potential is the hallmark of stem cells, we undertook a detailed phenotypic and functional characterization of human mammospheres over long-term passages. Methodology: Single cell suspensions derived from human breast `organoids' were seeded in ultra low attachment plates in serum free media. Resulting primary mammospheres after a week (termed T1 mammospheres) were subjected to passaging every 7th day leading to the generation of T2, T3, and T4 mammospheres. Principal Findings: We show that primary mammospheres contain a distinct side-population (SP) that displays a CD24(low)/CD44(low) phenotype, but fails to generate mammospheres. Instead, the mammosphere-initiating potential rests within the CD44(high)/CD24(low) cells, in keeping with the phenotype of breast cancer-initiating cells. In serial sphere formation assays we find that even though primary (T1) mammospheres show telomerase activity and fourth passage T4 spheres contain label-retaining cells, they fail to initiate new mammospheres beyond T5. With increasing passages, mammospheres showed an increase in smaller sized spheres, reduction in proliferation potential and sphere forming efficiency, and increased differentiation towards the myoepithelial lineage. Significantly, staining for senescence-associated beta-galactosidase activity revealed a dramatic increase in the number of senescent cells with passage, which might in part explain the inability to continuously generate mammospheres in culture. Conclusions: Thus, the self-renewal potential of human breast stem cells is exhausted within five in vitro passages of mammospheres, suggesting the need for further improvisation in culture conditions for their long-term maintenance