Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of Proliferative Diabetic Retinopathy in Juvenile-Onset Type I Diabetes: A 40-yr Follow-up Study

The development of proliferative diabetic retinopathy was studied in three cohorts consisting of 292 patients with recent juvenile-onset, type I (insulin-dependent) diabetes who were followed 20–40 yr beginning in 1939, 1949, and 1959. The risk of this severe eye complication was almost nonexistent during the first 10 yr of diabetes, rose abruptly to its maximum level (∼30/1000 person-years), and remained at that level for the next 25 yr. This pattern did not vary with sex, age at onset of diabetes, or level of glycemic control during the first 5 yr of diabetes. However, the risk of proliferative retinopathy was strongly related to the level of glycemic control during the several years preceding onset of this complication. This was a dose-dependent relationship, with patients in the highest quartile of the distribution of the index of frequency of hyperglycemia having a 10-fold higher risk than individuals in the lowest quartile. A virtually identical pattern was observed in patients who developed diabetes in 1959 as was observed in those who developed diabetes in 1949 or 1939. In contrast, diabetic nephropathy as evidenced by persistent proteinuria showed a lower incidence in the 1959 than in the 1939 cohort. In conclusion, these incidence data do not support the notion that the risk of proliferative retinopathy is mainly a function of duration of diabetes. Instead, the pattern of occurrence of this severe eye complication in type I diabetes suggests that the process leading to the development of proliferative retinopathy consists of two or more stages and that progression through each stage may be governed by different factors.
RNA–protein hybrid ribozymes that efficiently cleave any mRNA independently of the structure of the target RNA

Ribozyme activity in vivo depends on achieving high-level expression, intracellular stability, target colocalization, and cleavage site access. At present, target site selection is problematic because of unforeseeable secondary and tertiary RNA structures that prevent cleavage. To overcome this design obstacle, we wished to engineer a ribozyme that could access any chosen site. To create this ribozyme, the constitutive transport element (CTE), an RNA motif that has the ability to interact with intracellular RNA helicases, was attached to our ribozymes so that the helicase-bound, hybrid ribozymes would be produced in cells. This modification significantly enhanced ribozyme activity in vivo, permitting cleavage of sites previously found to be inaccessible. To confer cleavage enhancement, the CTE must retain helicase-binding activity. Binding experiments demonstrated the likely involvement of RNA helicase(s). We found that attachment of the RNA motif to our tRNA ribozymes leads to cleavage in vivo at the chosen target site regardless of the local RNA secondary or tertiary structure.
Large-Scale Targeted Proteomics Using Internal Standard Triggered-Parallel Reaction Monitoring (IS-PRM)*

Targeted high-resolution and accurate mass analyses performed on fast sequencing mass spectrometers have opened new avenues for quantitative proteomics. More specifically, parallel reaction monitoring (PRM) implemented on quadrupole-orbitrap instruments exhibits exquisite selectivity to discriminate interferences from analytes. Furthermore, the instrument trapping capability enhances the sensitivity of the measurements. The PRM technique, applied to the analysis of limited peptide sets (typically 50 peptides or less) in a complex matrix, resulted in an improved detection and quantification performance as compared with the reference method of selected reaction monitoring performed on triple quadrupole instruments. However, the implementation of PRM for the analysis of large peptide numbers requires the adjustment of mass spectrometry acquisition parameters, which affects dramatically the quality of the generated data, and thus the overall output of an experiment. A newly designed data acquisition scheme enabled the analysis of moderate-to-large peptide numbers while retaining a high performance level. This new method, called internal standard triggered-parallel reaction monitoring (IS-PRM), relies on added internal standards and the on-the-fly adjustment of acquisition parameters to drive in real-time measurement of endogenous peptides. The acquisition time management was designed to maximize the effective time devoted to measure the analytes in a time-scheduled targeted experiment. The data acquisition scheme alternates between two PRM modes: a fast low-resolution “watch mode” and a “quantitative mode” using optimized parameters ensuring data quality. The IS-PRM method exhibited a highly effective use of the instrument time. Applied to the analysis of large peptide sets (up to 600) in complex samples, the method showed an unprecedented combination of scale and analytical performance, with limits of quantification in the low amol range. The successful analysis of various types of biological samples augurs a broad applicability of the method, which is likely to benefit a wide range of proteomics experiments.
Antimanic efficacy of topiramate in 11 patients in an open trial with an on-off-on design.

BACKGROUND A series of open studies suggests that topiramate has efficacy in bipolar disorder. To further investigate the potential value of topiramate as an antimanic agent, we conducted an open trial in 11 manic patients. METHOD Eleven patients with bipolar I disorder with an acute manic episode (DSM-IV) were treated with a mood stabilizer and/or antipsychotics in sufficient and fixed doses. All had a Young Mania Rating Scale (YMRS) score of at least 24 (mean +/- SD = 33.5+/-8.1). Topiramate was added after stable plasma levels of concomitant mood stabilizers had been reached and was titrated within 1 week to a final dose in the range of 25 to 200 mg/day, depending on clinical efficacy and tolerability. Topiramate was discontinued after 10 days, while concomitant medication remained unchanged. After 5 days, topiramate was reintroduced at similar or increased dosages for another 7 days. Patients were assessed with the YMRS; the Clinical Global Impressions scale version for bipolar patients; and the 21-item Hamilton Rating Scale for Depression. RESULTS Seven of the 11 patients initially showed a good antimanic response with > 50% reduction in YMRS score. One patient showed psychotic features following rapid increase in topiramate dosage and dropped out on day 10. After discontinuation of topiramate, 7 of the remaining 10 patients worsened (increase of > or = 25% in YMRS score), 2 remained stable, and 1 discontinued follow-up after good recovery. After reintroducing topiramate, all patients improved again within a week, with 8 of 9 meeting the responder criterion of > or = 50% YMRS score reduction when comparing baseline values with those of day 22. With the exception of the patient who developed psychosis, topiramate was well tolerated. Concomitant medication did not interfere with plasma levels of drug, except for carbamazepine level in 1 patient. CONCLUSION The antimanic response among patients in this study appears reproducibly linked to the addition of topiramate.
Regional differences in gastric acidity and antacid distribution: is a single pH electrode sufficient?

UNLABELLED Accurate measurement of intragastric acidity has both clinical and investigational importance in studying gastric pathophysiology. OBJECTIVES The aims of this study were fourfold: (1) to investigate whether regional differences in intragastric acidity exist; (2) to determine intragastric acidity after a standard antacid was administered in both the fasting and fed states; (3) to monitor gastric emptying of and anatomic distribution of radiolabeled antacid during fasting and postprandial periods; and (4) to determine whether the regional effects of ingested antacid correlated with the anatomic distribution of the antacid. METHODS Eight normal male volunteers were studied after fluoroscopically guided nasogastric placement of a tube assembly containing four pH electrodes, with one electrode in each quartile of the stomach. Simultaneous pH readings were made from the four electrodes while fasting, after administration of fasting antacid (30 ml, 79 mEq buffering capacity), postprandially, and after postprandial antacid ingestion. All subjects repeated the protocol on a separate day, five of them using radiolabeled antacid. Gastric emptying and gastric distribution over time of radiolabeled antacid were determined for comparison to regional intragastric acidity. RESULTS Intragastric acidity varied regionally over time in response to meals and to fasting and postprandial antacid. In the fasting state, intragastric acidity returned to baseline after antacid ingestion in a proximal to distal (cardia to antrum) sequence, while postprandial antacid resulted in a return to baseline acidity in a distal to proximal (antrum to cardia) sequence. Radiolabeled antacid distribution paralleled intragastric pH and hydrogen ion concentration in the fasting state, with 82% of the antacid localizing in the distal half of the stomach within the first minute after antacid ingestion. Postprandially, the greatest initial and most prolonged antacid buffering effect occurred proximally, correlating with the presence of radiolabeled antacid. Postprandial antacid remained in the stomach for a longer time (T1/2 = 93.1 +/- 23.4 min) compared with fasting antacid (T1/2 = 23.6 +/- 11.1 min). CONCLUSIONS Measurement of acidity in the four quartiles of the stomach demonstrated regional variation in response to both food and a standard antacid. A single pH electrode does not detect regional intragastric pH differences.
Cyclooxygenase‐2 is induced in the endothelial cells throughout the central nervous system during carrageenan‐induced hind paw inflammation; its possible role in hyperalgesia

Inflammation is often accompanied with hyperalgesia. This hyperalgesia is mediated partly by prostaglandin(s) produced in the CNS through the cyclooxygenase‐2 (COX‐2) dependent pathway. However, it remains unclear where COX‐2 is induced in the CNS during inflammation, and how it is involved in hyperalgesia. We studied the precise site of COX‐2 induction in the CNS, the relation between the time course of COX‐2 induction and that of hyperalgesia, and the effect of COX‐2‐selective inhibitor by using a carrageenan model. Carrageenan injection induced expression of COX‐2‐like immunoreactivity in vascular endothelial cells throughout the CNS. This response became evident by 3 h, and was most prominent at 6 h after carrageenan injection. This COX‐2 induction was associated with an elevation of prostaglandin E2 in the cerebrospinal fluid, being evident at 3 h, larger at 6 h, and alleviated by a COX‐2‐selective inhibitor. Thermal hyperalgesia became evident at 1 h, further increased thereafter, and remained elevated until 6 h. Intrathecal administration of COX‐2‐selective inhibitor 2 h after the carrageenan injection exerted a prominent therapeutic effect on hyperalgesia. These results demonstrate that, during carrageenan‐induced inflammation, endothelial cells are the major source of prostaglandin(s) in the CNS, and this endothelial expression of COX‐2 is involved in the inflammation‐induced hyperalgesia.
Cocaine, norcocaine, ecgonine methylester and benzoylecgonine pharmacokinetics in the rat.

We have compared the pharmacokinetics of bolus dose cocaine administration with that of its three most important metabolites; norcocaine, ecgonine methylester, and benzoylecgonine and assessed whether kinetics are dose dependent at two equimolar doses equivalent to cocaine hydrochloride 2.5 and 5 mg/kg respectively. Forty-nine male Sprague-Dawley rats were randomly divided into 8 groups to receive i.v. either high (14.7 umol/kg) (HI) or low (7.3 umol/kg) (LO) bolus doses of cocaine or one of its metabolites. Arterial blood samples for cocaine and metabolite analysis were taken repetitively over the next 3 h. Equimolar bolus doses of these congeners showed biexponential plasma concentration decay curves which were fitted to a two compartment model and subjected to noncompartmental analysis. The plasma concentration time profiles were significantly different for the HI and LO doses administered for each congener. The elimination half-lives of cocaine and norcocaine were similar (28-33 min), that for ecgonine methylester (60-71 min) was approximately twice this and for benzoylecgonine was 40-44 min. Cocaine clearance (155-158 ml/kg/min) was found to be in the range found in other rat studies. Ecgonine methylester clearance and benzoylecgonine clearance were found to be one quarter and one eighth of this value respectively. The pharmacokinetic profile of these congeners was not dose dependent when the two doses administered were compared.
The significance of a collaborative practice model in delivering care to chronically ill patients: A case study of managing diabetes mellitus in a primary health care center

Non-communicable diseases, especially diabetes mellitus type two (DM2) constitute major health problems in Lebanon that have an adverse impact on health and health resources. Collaborative practice interventions may improve quality care of DM2 and reduce or delay complications. The purpose of this paper was to evaluate the impact of collaborative practice on the quality and cost of effective care for diabetic patients in a primary health care center. A chart audit review of 375 diabetic patients attending an inner city health center in Beirut (Lebanon) was conducted after three and a half years of collaborative practice intervention, which included guidelines for an interdisciplinary health team. Evaluation of the impact of collaborative practice was conducted on the process and outcome of care. The results indicated a high level of enthusiasm, support and the development of team spirit at the process level. At the outcome level there was improvement in documentation, increase in patient recruitment, increase in continuity of care, improvement of glycemic control and decreased cost. In conclusion collaborative practice interventions improved process and outcome variables for diabetic patients. It is suggested that this model could be developed for use in the care of other chronic diseases.
Calcium-activated potassium channels – a therapeutic target for modulating nitric oxide in cardiovascular disease?

Importance of the field: Cardiovascular risk factors are often associated with endothelial dysfunction, which is also prognostic for occurrence of cardiovascular events. Endothelial dysfunction is reflected by blunted vasodilatation and reduced nitric oxide (NO) bioavailability. Endothelium-dependent vasodilatation is mediated by NO, prostacyclin, and an endothelium-derived hyperpolarising factor (EDHF), and involves small (SK) and intermediate (IK) conductance Ca2+-activated K+ channels. Therefore, SK and IK channels may be drug targets for the treatment of endothelial dysfunction in cardiovascular disease. Areas covered in this review: SK and IK channels are involved in EDHF-type vasodilatation, but recent studies suggest that these channels are also involved in the regulation of NO bioavailability. Here we review how SK and IK channels may regulate NO bioavailability. What the reader will gain: Opening of SK and IK channels is associated with EDHF-type vasodilatation, but, through increased endothelial cell Ca2+ influx, l-arginine uptake, and decreased ROS production, it may also lead to increased NO bioavailability and endothelium-dependent vasodilatation. Take home message: Opening of SK and IK channels can increase both EDHF and NO-mediated vasodilatation. Therefore, openers of SK and IK channels may have the potential of improving endothelial cell function in cardiovascular disease.
Environmental and Societal Attitudes to Working Hours in Gendered Perspective: Patterns, Preferences and Policy

ABSTRACT This article begins from the premise that environmental degradation is a profound and present threat and that work time reduction–with an associated reduction in consumption–is one of a number of strategies that can be adopted to combat it. As a precursor to looking at how such policies can be supported, our research questions whether environmental attitudes are congruent with work time patterns and preferences. Our initial hypothesis was that those who care most for the environment would work fewer hours than those who exhibit lower levels of environmental concern, and prefer to do so. However, contra our expectations, our empirical analysis of the European Social Survey shows that those who state they care most about the environment are more likely to work longer hours, and prefer to do so. Overall, men tend to be less concerned about the environment, and work longer. Caring responsibilities, in contrast, fall disproportionately on women. We argue that this reflects traditional gender roles that are a residual from the social norm of the male breadwinner model. Given work time reduction as an environmental policy, the task is to influence preferences and ‘green’ human behaviour, especially among men.
The Complex Cell Wall Composition of Syncytia Induced by Plant Parasitic Cyst Nematodes Reflects Both Function and Host Plant

Plant–parasitic cyst nematodes induce the formation of specialized feeding structures, syncytia, within their host roots. These unique plant organs serve as the sole nutrient resource for development and reproduction throughout the biotrophic interaction. The multinucleate syncytium, which arises through local dissolution of cell walls and protoplast fusion of multiple adjacent cells, has dense cytoplasm containing numerous organelles, surrounded by thickened outer cell walls that must withstand high turgor pressure. However, little is known about how the constituents of the syncytial cell wall and their conformation support its role during nematode parasitism. We used a set of monoclonal antibodies, targeted to a range of plant cell wall components, to reveal the microstructures of syncytial cell walls induced by four of the most economically important cyst nematode species, Globodera pallida, Heterodera glycines, Heterodera avenae and Heterodera filipjevi, in their respective potato, soybean, and spring wheat host roots. In situ fluorescence analysis revealed highly similar cell wall composition of syncytia induced by G. pallida and H. glycines. Both consisted of abundant xyloglucan, methyl-esterified homogalacturonan and pectic arabinan. In contrast, the walls of syncytia induced in wheat roots by H. avenae and H. filipjevi contain little xyloglucan but are rich in feruloylated xylan and arabinan residues, with variable levels of mixed-linkage glucan. The overall chemical composition of syncytial cell walls reflected the general features of root cell walls of the different host plants. We relate specific components of syncytial cell walls, such as abundant arabinan, methyl-esterification status of pectic homogalacturonan and feruloylation of xylan, to their potential roles in forming a network to support both the strength and flexibility required for syncytium function.
Telemedicine in rural care. Part 2: Assessing the wider issues.

BACKGROUND The first article about this development (Macduff et al 2001) described the evolution of a nurse-led telemedicine service in the village of Hamlet (population 1,600), north-east Scotland, and presented the findings of an evaluation study. In this second article, those findings are discussed in relation to the wider picture of nursing involvement in teleconsultation. The village has no medical practice or pharmacy and the majority of Hamlet's residents aged over 65 are registered with the Bradieslea Road surgery, one of three general practices six miles away in the town of Bradieslea. The community nursing service is based in small rooms at a sheltered housing complex in the village. This service covers all patients in the Hamlet area. It is staffed by one full-time district nurse/health visitor (who acts as team leader) and one part-time district nurse. Both are qualified nurse prescribers. CONCLUSION Opportunities now exist for nurses to use teleconsultation for the benefit of their patients. A systematic development of this type of nursing role through integration with broader service development would be valuable.
Coplanar 122-GHz Antenna Array With Air Cavity Reflector for Integration in Plastic Packages

This letter introduces the concept of a surface-mountable millimeter-wave radar sensor, which becomes possible by integrating the complete radar front end including the antennas into a single plastic package. The packaging concept is based on a matched coplanar wire-bond interconnect between the semiconductor die and the off-chip antenna. A 122-GHz antenna design is presented that uses an air cavity within the center die pad to improve the bandwidth-efficiency product. The antenna is designed in an array configuration to reduce the effect of surface waves. Measurements of the antenna prototype in the package, as well as a study on the influence of the package lid on the antenna performance, are given.
Depth estimation to manage visual signal loss during visual servoing with a 3 DOF camera

This paper deals with the problem of estimating the visual features during a vision-based navigation task when a temporary total occlusion occurs. The proposed approach relies on an existent specific algorithm. However, to be efficient, this algorithm requires highly precise initial values for both the image features and their depth. Thus, our objective is to design a predictor/estimator pair able to provide an accurate estimation of the depth value, even when the visual data are noisy. We also aim at obtaining a method reducing the implementation complexity while preserving performances. The obtained results show the efficiency and the interest of our technique.
The inevitable deservingness gap: A study into the insurmountable immigrant penalty in perceived welfare deservingness

As the asylum crisis hit Europe in tandem with the Great Recession, concerns about declining support for equal welfare provision to immigrants grow. Although studies on welfare deservingness show that immigrants are deemed least entitled to welfare compared to other target groups, they have fallen short of isolating welfare claimants’ identity (i.e. foreign origin) with competing deservingness criteria that might explain the immigrant deservingness gap. This article studies the importance of welfare claimants’ foreign origins relative to other theoretically relevant deservingness criteria via a unique vignette experiment among 23,000 Dutch respondents about their preferred levels of unemployment benefits. We show that foreign origin is among the three most important conditions for reduced solidarity, after labour market reintegration behaviour (reciprocity) and culpability for unemployment (control). Furthermore, favourable criteria do not close the gap between immigrants and natives in perceived deservingness, emphasizing the difficulty of overcoming the immigrant penalty in perceived welfare deservingness. We conclude our findings in the light of ongoing theoretical and political debates.
Cloning, nucleotide sequence determination and expression of the genes encoding cytochrome P‐450soy and ferredoxinsoy (soyB) from Streptomyces griseus

Xenobiotic transformation by Streptomyces griseus (ATCC13273) is catalysed by a cytochrome P‐450, designated cytochrome P‐450soy A DNA segment carrying the structural gene encoding P‐450soy (soyC) was cloned using an oligonucleotide probe constructed from the protein sequence of a tryptic peptide. Following DNA sequencing the deduced amino acid sequence of P‐450soy was compared with that for P‐450cam, revealing conservation of important structural components including the haem pocket. Expression of the cloned soyC gene product was demonstrated in Streptomyces lividans by reduced CO:difference spectral analysis and Western blotting. Downstream of soyC, a gene encoding a putative [3Fe‐4S] ferredoxin (soyB), named ferredoxinsoy, was identified.