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Purpose Lax eyelid condition (LEC) and floppy eyelid syndrome (FES) represent two distinct conditions which have been associated with several ocular and systemic comorbidities. The main aim of this systematic review and meta-analysis is to explore the available literature to estimate the prevalence rate of LEC and FES in obstructive sleep apnea (OSA). Methods The protocol of this systematic review and meta-analysis has been registered in PROSPERO. Four electronic databases (PubMed/MEDLINE, Google Scholar, Cochrane Library, Web of Science) were searched from inception to December 24, 2021. A random intercept logistic regression model was carried out for the analysis of overall proportions. Odds ratio and mean difference were reported as measures of the effect size in the presence of binary and continuous outcomes, respectively. The estimated numbers of LEC/FES patients in OSA were calculated by multiplying the prevalence rate determined by our random-effects model and the corresponding Benjafield et al.’s population prospect. Results We included 11 studies comprising 1225 OSA patients of whom 431 and 153 affected by LEC and FES, respectively. Our model estimated a pooled prevalence rate for LEC and FES in OSA patients of 40.2% (95%CI: 28.6–53.1%) and of 22.4% (95%CI: 13.8–34.2%), respectively. The number of LEC/FES affected individuals among OSA patients is expected to peak up to 376 and to 210 million, respectively. OSA patients appeared to have a 3.4 (95%CI: 2.2–5.2) and a 3.0 (95%CI: 1.7–5.5) increased risk of developing LEC and FES than the healthy counterpart. Conclusion Prevalence of LEC and FES is higher in OSA-affected patients compared to controls. More studies are warranted to investigate the mechanisms leading to the development of LEC and/or FES in OSA patients, as well as the feasibility of the adoption of these clinical findings as screening tools for OSA.

To accurately time motor responses when intercepting falling balls we rely on an internal model of gravity. However, whether and how such a model is also used to estimate the spatial location of interception is still an open question. Here we addressed this issue by asking 25 participants to intercept balls projected from a fixed location 6 m in front of them and approaching along trajectories with different arrival locations, flight durations, and gravity accelerations (0 g and 1 g). The trajectories were displayed in an immersive virtual reality system with a wide field of view. Participants intercepted approaching balls with a racket, and they were free to choose the time and place of interception. We found that participants often achieved a better performance with 1 g than 0 g balls. Moreover, the interception points were distributed along the direction of a 1 g path for both 1 g and 0 g balls. In the latter case, interceptions tended to cluster on the upper half of the racket, indicating that participants aimed at a lower position than the actual 0 g path. These results suggest that an internal model of gravity was probably used in predicting the interception locations. However, we found that the difference in performance between 1 g and 0 g balls was modulated by flight duration, the difference being larger for faster balls. In addition, the number of peaks in the hand speed profiles increased with flight duration, suggesting that visual information was used to adjust the motor response, correcting the prediction to some extent. NEW & NOTEWORTHY Here we show that an internal model of gravity plays a key role in predicting where to intercept a fast-moving target. Participants also assumed an accelerated motion when intercepting balls approaching in a virtual environment at constant velocity. We also show that the role of visual information in guiding interceptive movement increases when more time is available.

In rat striatum A(2A) adenosine receptors activate adenylyl cyclase through coupling to G(s)-like proteins, mainly G(olf) that is expressed at high levels in this brain region. In this study we report that the sulfhydryl alkylating reagent, N-ethylmaleimide (NEM), causes a concentration- and time-dependent inhibition of [3H] 2-p-(2-carboxyethyl)phenylethylamino)-5'-N-ethylcarboxamido adenosine ([3H]CGS21680) binding to rat striatal membranes. Membrane treatment with [14C]N-ethylmaleimide ([14C]NEM) labels numerous proteins while addition of 5'-guanylylimidodiphosphate (Gpp(NH)p) reduces labeling of only three protein bands that migrate in SDS-polyacrylamide gel electrophoresis with apparent molecular masses of approximately 52, 45 and 39 kDa, respectively. The 52- and 45-kDa labeled bands show electrophoretic motilities as Galpha(s)-long and Galpha(s)-short/Galpha(olf) subunits. An anti-Galpha(s/olf) antiserum immunoprecipitates two 14C labeled bands of 44 and 39 kDa. The band density decreases by 21-26% when membranes are treated with NEM in the presence of Gpp(NH)p. An anti-A(2A) receptor antibody also immunoprecipitates two 14C labeled bands of 40 and 38 kDa, respectively. However, such protein bands do not show any decrease of their density upon membrane treatment with NEM plus Gpp(NH)p. These results indicate that in rat striatal membranes NEM alkylates sulfhydryl groups of both Galpha(s/olf) subunits and A(2A) adenosine receptors. In addition, cysteine residues of Galpha(s/olf) are easily accessible to modification when the subunit is in the GDP-bound form. The 39- and 38-kDa labeled proteins may represent proteolytic fragments of Galpha(s/olf) and A(2A) adenosine receptor, respectively.

The pharmacological properties of endothelin receptors (ETR) were investigated in guinea-pig bronchus by comparing binding and functional results. In binding assays, both the ETB agonists, endothelin-3 (ET-3) and N-suc-[Glu9,Ala11,15]ET-1(8–21) (IRL 1620), and the antagonist, N-cis-2,6-dimethylpiperidinocarbonyl-L-γ-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine (BQ 788), showed biphasic inhibition curves of [125I]-endothelin-1 (ET-1) binding to bronchus membranes prepared from intact or epithelium-deprived tissue. IRL 1620 did not completely displace specifically [125I]-ET-1 bound to these tissue preparations. In the presence of the ETA-selective antagonist, cyclo(-D-Trp-D-Asp-L-Pro-D-Val-L-Leu) (BQ 123, 1 μM), IRL 1620 displacement curves were shallow but a complete inhibition was reached at a concentration of 1 μM. Both curves were better represented by two-site models. In addition, BQ 788 competition curves became monophasic when binding experiments were performed in the presence of 1 μM BQ 123. The non-selective agonist, ET-1, and BQ 123 inhibited [125I]-ET binding to bronchus membranes in dose-dependent fashions with monophasic curves. The contracting activity of IRL 1620 (0.55 nM–1.6 μM) was tested on multiple-ring bronchial preparations pretreated with peptidase and cyclo-oxygenase inhibitors. BQ 788 shifted IRL1620 concentration-response curves to the right while BQ 123 did not influence bronchial responsiveness. In addition, a potentiation of the maximal response to the agonist was observed in BQ 788 treated bronchial rings. This effect was abolished by tissue pretreatment with Nω-nitro-L-argininemethylester (L-NAME) or epithelium removal but not by pretreatment with atropine or iberiotoxin. Our results demonstrate that guinea-pig bronchus contains two populations of ETB receptors with different affinities for the ETB-selective agonist, IRL 1620. One ETB receptor population appears to activate bronchial muscle contraction while another on epithelial cells causes muscle relaxation through the release of nitric oxide (NO). Keywords: Endothelin receptors, ETB receptors, endothelins, guinea-pig bronchus Introduction Endothelins (ETs)1, a family of three closely related peptide hormones, endothelin-1, -2, and -3 (ET-1, ET-2, and ET-3), were originally recognized as potent modulators of vascular functions participating in both vasoconstriction and vasodilatation. Thereafter, the presence of ETs was demonstrated in several other tissues of different species including humans, where they exert various physiological effects (for a review see: Rubanyi & Polokoff, 1994; Webb et al., 1998). All activities of ETs are mediated through the interaction with specific cell surface receptors (for a review see: Bax & Saxena, 1994; Ohlstein et al., 1996; Pollock et al., 1995). Two ETR subtypes, termed ETA and ETB, have been identified, cloned and expressed from rat (Lin et al., 1991; Sakurai et al., 1990; Sugiura et al., 1989), bovine (Arai et al., 1990; Saito et al., 1991), and human tissues (Adachi et al., 1991; Cyr et al., 1991; Ogawa et al., 1991; Sakamoto et al., 1991). Both receptor subtypes belong to the large receptor family characterized by seven transmembrane-spanning regions which regulate distinct intracellular signalling pathways through the activation of G proteins. The two subtypes can be distinguished by different rank orders of affinity toward the three ET isopeptides. The ETA receptor binds ET-1, ET-2 and ET-3 with decreasing affinities whereas the ETB receptor shows a similar affinity for all three isopeptides. An additional classification of both receptor subtypes as ETA1, ETA2, ETB1, and ETB2 has been proposed on the basis of their affinities for agonists or antagonists (Karaki et al., 1994; Sudjarwo et al., 1994). The ETA receptor mediates contraction of arterial smooth muscles, while the ETB receptor exhibits either contractile or relaxing effects depending on the vascular bed examined (Pollock et al., 1995). Selective activation of ETB receptors on endothelial cells causes relaxation of rat aorta through the release of nitric oxide (Karaki et al., 1993). However, activation of ETB receptors on venous smooth muscles gives rise to vasoconstriction (Moreland et al., 1994). ETs modulate airway activities of different species including humans (Hay et al., 1993; Knott et al., 1995). These peptides are potent constrictors of airways both in vivo and in vitro (Hay et al., 1993; Touvay et al., 1990). In guinea-pig trachea and bronchus, the contraction induced by ET-1 appears to involve a mixed population of ETRs (Hay et al., 1993). In addition, regional differences of ETR subtype distribution seem to exist in guinea-pig airways, with bronchus expressing mainly ETB receptor subtypes (Hay et al., 1993). In guinea-pig trachea, functional (Battistini et al., 1993) and autoradiographic studies (Tschirhart et al., 1991) have shown the presence of ETRs on the epithelium. Functional data reported by Battistini et al. (1993) have also indicated that in guinea-pig trachea, ET-1 activates ETA receptors on epithelial cells, inducing the release of prostanoids, while airway contraction is mediated via ETB receptors probably present on smooth muscles. Recently, it has been suggested (Yoneyama et al., 1995b) that ETs modulate the airway tone by acting not only directly on airway smooth muscle, but also on the cholinergic nerve, to modulate acetylcholine (ACh) release. The pathophysiological role of ETs in asthma and other respiratory disorders has received some attention (Hay et al., 1993). The presence of ETB receptors in guinea-pig and human bronchus mediating smooth muscle contraction is well established (Battistini et al., 1994; Hay et al., 1993; 1998; Hay & Luttman, 1997). However, in guinea-pig this receptor population has not been characterized for its biochemical and pharmacological features. Two subtypes of ETA and ETB receptors seem to mediate smooth muscle contraction of rabbit trachea (Yoneyama et al., 1995a). Similarly, the ETB receptor population in guinea-pig bronchus cannot be homogeneous. As guinea-pig bronchus is frequently used as an experimental model to test the activity of new anti-asthmatic drugs, characterization of its ETB receptor population is pivotal for elucidating the pathophysiological significance of ETs in asthma. Thus, we investigated the biochemical and pharmacological properties of ETRs in guinea-pig bronchus using selective agonist and antagonist ligands.

Increased expression of urokinase (uPA), a member of the serine protease family, is an effector of metastatic cascade and has been reported in various malignancies, including breast cancer. uPA overexpression in cancer tissues was correlated with a more aggressive phenotype and it is considered a strong and independent unfavorable prognostic factor in breast cancer. Using real-time PCR assay, we analyzed uPA expression of malignant and benign breast nodular lesions versus healthy tissues (normal breast and lymphocytes). We found that besides breast cancer nodule, normal mammary gland and lymphocytes overexpressed uPA too. Tissues obtained from women with benign lesions expressed homogeneous and lower uPA. In conclusion, although uPA overexpression is typical of cancer tissues, it could be considered as a feature of the whole organism affected by cancer. On the basis of these first results, uPA could be considered for further studies as a possible useful therapeutic target in breast cancer.