Harmonizing Disability Data To Improve Disability Research And Policy.

Disability is complex and multifaceted, complicating governments' efforts to collect the high-quality, comprehensive data necessary for developing, implementing, and monitoring policies. Yet data are needed to obtain information on functioning in the population, to identify the population with disabilities, and to disaggregate indicators of well-being by disability to determine whether people with disabilities are participating in society to the same extent as those without disabilities. In this article we discuss the need for data harmonization to improve disability research and policy.

The Influence of Positive End-Expiratory Pressure on Leakage and Oxygenation Using a Laryngeal Mask Airway: A Randomized Trial.

Background: The value of positive end-expiratory pressure (PEEP) in maintaining oxygenation during ventilation with a laryngeal mask airway (LMA) mask is unclear. To clarify the potential benefit or harm to PEEP application during positive pressure ventilation with a ProSeal LMA® mask, we compared the effect of PEEP versus zero end-expiratory pressure (ZEEP) on gas leakage and oxygenation. We hypothesized that a PEEP of 8 mbar (8.

Children Living in Households That Experienced Food Insecurity: United States, 2019-2020.

Food insecurity, which affects an estimated 15 million Americans (1), is the limited or uncertain availability of safe and nutritionally adequate foods, or the limited or uncertain ability to acquire acceptable foods in socially acceptable ways (2). Food insecurity has been consistently associated with poor health outcomes in children, including poorer overall health status, acute and chronic health problems, and limited healthcare access (3). This report describes the percentage of children aged 0-17 years living in food-insecure households during the past 30 days by selected sociodemographic and family characteristics using 2019-2020 National Health Interview Survey data.

Stressful Life Events Among Children Aged 5-17 Years by Disability Status: United States, 2019.

Children with disabilities are at increased risk of experiencing stressful life events (1,2). These events include various forms of abuse, neglect, and household instability, such as exposure to violence, parental or guardian incarceration, and living with someone with mental illness or alcohol or drug problems (3). Stressful life events experienced in childhood may have lifelong effects on physical and mental health outcomes (4-11), as well as socioeconomic outcomes, including educational attainment and employment (12).

Disparities in Stressful Life Events Among Children Aged 5-17 Years: United States, 2019.

Stressful life events in childhood include various forms of abuse, neglect, and household instability, such as violence exposure, parental incarceration, or living with someone with mental health, alcohol, or drug problems (1). These events are key social determinants of a child's well-being and can have lifelong impacts on physical and mental health (2-9). This report presents sociodemographic disparities in stressful life events as reported by a knowledgeable adult, usually a parent, among children aged 5-17 years using the 2019 National Health Interview Survey data.

Addressing health inequalities in Latin America: the role of social protection.

After more than a decade of progress in various areas of social development, since 2015 poverty has increased, labor market indicators have deteriorated, and the reduction of income inequality has stagnated in Latin America. These trends are of concern as they can affect health indicators and exacerbate profound health inequalities. This situation demands integrated policy responses that can create synergies between different sectors.

Synthesis and structure-activity relationships of suramin-derived P2Y11 receptor antagonists with nanomolar potency.

Selective and potent P2Y(11) receptor antagonists have yet to be developed, thus impeding an evaluation of this G protein-coupled receptor mainly expressed on immune cells. Taking suramin with moderate inhibitory potency as a template, 18 ureas with variations of the methyl groups of suramin and their precursors were functionally tested at P2Y(11), P2Y(1), and P2Y(2) receptors. Fluorine substitution of the methyl groups of suramin led to the first nanomolar P2Y(11) antagonist (8f, NF157, pK(i): 7.

The novel suramin analogue NF864 selectively blocks P2X1 receptors in human platelets with potency in the low nanomolar range.

The role of ATP-stimulated P2X1 receptors in human platelets is still unclear. They may act alone or in synergy with other pathways, such as P2Y1 or P2Y12 receptors, to accelerate and enhance calcium mobilisation, shape change and aggregation. To date very few pharmacological means of selectively inhibiting platelet P2X1 receptors have been described, although recent work has shown that suramin is a useful lead compound for the development of high-affinity P2X1 antagonists.

Use-dependent inhibition of the skeletal muscle ryanodine receptor by the suramin analogue NF676.

The skeletal muscle Ca2+ release channel, the ryanodine receptor, is activated by the trypanocidal drug suramin via the calmodulin-binding site. As calmodulin activates and inhibits the ryanodine receptor depending on whether Ca2+ is absent or present, suramin analogues were screened for inhibition of the ryanodine receptor. Up to 300 microM, the novel suramin analogue, 4,4'-(carbonyl-bis(imino-4,1-phenylene-(2,5-benzimidazolylene)carbonylimino))-bis-benzenesulfonic acid disodium salt (NF676) was not able to significantly inhibit the basal [3H]ryanodine binding.

Inhibition of platelet functions and thrombosis through selective or nonselective inhibition of the platelet P2 receptors with increasing doses of NF449 [4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis-(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid octasodium salt].

Our aim was to determine whether the newly described P2X1 antagonist NF449 [4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid octasodium salt] could selectively antagonize the platelet P2X1 receptor and how it affected platelet function. NF449 inhibited alpha,beta-methyleneadenosine 5'-triphosphate-induced shape change (IC50 = 83 +/- 13 nM; n = 3) and calcium influx (pA2 = 7.2 +/- 0.

Profiling at recombinant homomeric and heteromeric rat P2X receptors identifies the suramin analogue NF449 as a highly potent P2X1 receptor antagonist.

P2X receptors are cation channels gated by extracellular ATP and related nucleotides. Because of the widespread distribution of P2X receptors and the high subtype diversity, potent and selective antagonists are needed to dissect their roles in intact tissues. Based on suramin as a lead compound, several derivates have been described that block recombinant P2X receptors with orders of magnitude higher potency than suramin.

Structure-activity relationships of analogues of NF449 confirm NF449 as the most potent and selective known P2X1 receptor antagonist.

NF449 [4,4',4",4"'-(carbonylbis(imino-5,1,3-benzenetriyl-bis(carbonylimino)))tetrakisbenzene-1,3-disulfonic acid-octasodiumsalt)] was recently described to inhibit recombinant rP2X(1) receptors (Naunyn Schmiedeberg's Arch. Pharmacol. 364 (2001) 285).

Structure-activity relationships of suramin and pyridoxal-5'-phosphate derivatives as P2 receptor antagonists.

Extracellular adenine and uracil 5'-nucleotides are important signalling molecules that exert a great variety of effects in numerous tissues and cell types through the activation of P2 receptors. In the past eight years, an extended series of P2 receptors (P2X(17), ionotropic subunits; P2Y(1,2,4,6,11,12), metabotropic receptors) has been cloned from vertebrate tissues. In this rapidly expanding field, one of the main current challenges is to relate the cloned P2 receptor subtypes to the diverse physiological responses mediated by the pharmacological phenotypes of native P2 receptors.

NF449: a subnanomolar potency antagonist at recombinant rat P2X1 receptors.

Antagonistic effects of the novel suramin analogue 4,4',4",4"'-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid (NF449) were studied on contractions of the rat vas deferens elicited by alpha,beta-methylene ATP (alphabetameATP; mediated by P2X1 receptors), contractions of the guinea-pig ileal longitudinal smooth muscle elicited by alphabetameATP (mediated by P2X3 receptors) or adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS; mediated by P2Y1 receptors), ATP-induced increases of [Ca2+]i in human embryonic kidney (HEK) 293 cells (mediated by P2Y2 receptors), inward currents evoked by ATP in follicle cell-free Xenopus laevis oocytes expressing rP2X1 or rP2X3 receptors and degradation of ATP by ecto-nucleotidases in folliculated Xenopus laevis oocytes. In addition, NF449 was examined for its P2 receptor specificity in rat vas deferens (alpha1A-adrenoceptors) and guinea-pig ileum (histamine H1 and muscarinic M3 receptors). At native (pIC50=7.

Pathophysiologic role of contact activation in bleeding followed by thromboembolic complications after implantation of a ventricular assist device.

The time period after implantation of a ventricular assist device in patients with end-stage heart disease is complicated by hemorrhage in the early postoperative period and by thromboembolism in the later course. To investigate the pathophysiologic role of contact activation in 12 bridging patients (10 patients with a paracorporeal Berlin Heart [Berlin Heart GmbH, Berlin, Germany], 2 patients with an intracorporeal Novacor system [Novacor N100; Baxter, Oakland, CA]), hemostatic parameters were determined until heart transplantation or at least up to the 51st postoperative day. The following were observed: 1) In the early postoperative period, until day 15, levels of contact factors XI, XII, and prekallikrein were below normal, whereas levels of plasmin-a2-antiplasmin (PAP) complexes were elevated.