Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychiatric Disorders in Youths With IDDM: Rates and Risk Factors

OBJECTIVE To determine prevalence rates, associated features and risk factors for psychiatric disorders subsequent to the diagnosis of IDDM in youths. RESEARCH DESIGN AND METHODS Using a longitudinal, naturalistic design, 92 youths from 8 to 13 years old at onset of IDDM were followed from their initial diagnosis. They were repeatedly assessed by semistructured interview and diagnosed by operational criteria. RESULTS By the 10th year of IDDM and the mean age of 20 years, an estimated 47.6% of the sample developed psychiatric disorder. Major depressive, conduct, and generalized anxiety disorders were the most prevalent, and major depression had a significantly higher estimated rate (27.5%) than each other disorder. The highest incidence rates were during the 1st year of the medical condition. Initial maternal psychopathology increased the risk of psychiatric disorder in the subjects, and maternal depression was a specific risk factor for depression in the subjects. Earlier psychiatric disorder in the subjects also increased the risk of later disorder. CONCLUSIONS The results converge with findings from other studies, suggesting elevated psychiatric morbidity in contemporary samples of young people with IDDM. The morbidity partly reflects the high incidence of major depression in adolescence and generalized anxiety disorder in young adulthood. Monitoring the psychological status of young patients and their mothers may help to identify diabetic children at risk for psychiatric disorder and facilitate prevention or treatment efforts. Monitoring may be particularly beneficial during the 1st year of the IDDM.
Direct effect of Ca2+–calmodulin on cGMP‐activated Ca2+‐dependent Cl−channels in rat mesenteric artery myocytes

Recently a novel cGMP‐activated Ca2+‐dependent Cl−channel has been described in rat mesenteric artery smooth muscle cells. In the present work we have investigated the actions of calmodulin (CaM) on single channel cGMP‐activated Ca2+‐dependent Cl−current (ICl(cGMP,Ca)) in inside‐out patches. When 1 μm CaM was applied to the intracellular surface of inside‐out patches bathed with 10 μm cGMP and 100 nm[Ca2+]i there was approximately a 10‐fold increase in channel open probability (NPo). This effect of CaM was not observed with lower [Ca2+]i and 100 nm[Ca2+]i with 1 μm CaM did not activate Cl−channels in the absence of cGMP. The unitary conductance, reversal potential and mean open time of the single‐channel currents were similar in the absence or presence of CaM. With 10 μm cGMP and 100 nm[Ca2+]i the relationship between NPo and CaM concentration was well fitted by the Hill equation yielding an equilibrium constant for CaM of about 1.9 nm and a Hill coefficient of 1.7. With 1 μm CaM (+10 μm cGMP) the relationship between [Ca2+]i and NPo was also fitted by the Hill equation which yielded an apparent equilibrium constant of 74 nm[Ca2+]i and a Hill coefficient of 4.8. When [Ca2+]i was increased from 300 nm to 1 μm there was a decrease in NPo. The potentiating effect of CaM was markedly reduced by the selective CaM binding peptide Trp (5 nm) but not by the Ca2+/CaM‐dependent protein kinase II (CaMKII) inhibitor autocamtide II related inhibitory peptide (AIP). It is concluded that CaM potentiates the activity of single channel ICl(cGMP,Ca) by increasing the probability of channel opening via a CaMKII‐independent mechanism.
The epidemiology of hypernatraemia in hospitalised children in Lothian: a 10-year study showing differences between dehydration, osmoregulatory dysfunction and salt poisoning

Introduction The relative frequencies of the causes of hypernatraemia in children after the neonatal period are unknown. Salt poisoning and osmoregulatory dysfunction are extremely rare and potentially fatal. In this retrospective 10-year study, the incidence, causes and differential biochemistry of hypernatraemia in children is examined. Methods Children with hypernatraemia (sodium ≥150 mmol/litre) aged >2 weeks to 17 years were identified from laboratory data of two paediatric departments serving the Lothian region of Scotland. A review of patient notes established time of onset and cause. Denominator data were available from the Scottish Health Service. Results On admission to hospital, 1 in 2288 children (1:1535 admitted as an emergency) had hypernatraemia. This is 1 in 30 563 Lothian children <17 years. Overall 0.04% hospital stays had an episode of hypernatraemia. In 45 children admitted with 64 separate episodes (11 from a case of salt poisoning), the commonest cause was dehydration secondary to either gastroenteritis or systemic infection; 31% had an underlying chronic neurological disorder. A total of 177 further cases developed hypernatraemia after admission. The commonest causes were dehydration secondary to severe systemic infection and postoperative cardiac surgery. Urine sodium:creatinine ratio and fractional excretion of sodium were both much higher in the salt poisoning case than in a child with osmoregulatory dysfunction or children with simple dehydration. Conclusions Hypernatraemia after 2 weeks of age is uncommon, and on admission is usually associated with dehydration. Salt poisoning and osmoregulatory dysfunction are rare but should be considered in cases of repeated hypernatraemia without obvious cause. Routine measurement of urea, creatinine and electrolytes on paired urine and plasma on admission will differentiate these rare causes.
Thrombosis risk in systemic lupus erythematosus: the role of thrombophilic risk factors

Objectives: Thromboembolic episodes are frequent manifestations of systemic lupus erythematosus (SLE). Although the presence of anti‐phospholipid antibodies (aPL) is known to contribute to thromboembolism (TE), the relative contribution of other TE risk factors is unknown. The aim of this study was to determine the prevalence of TE in a Caucasian SLE population, to identify the risk factors of highest importance, and to assess the clinical value of thrombophilia screening among SLE patients. Methods: Samples from 105 patients were analysed with a screen including aPL, activated protein C resistance, factor V Leiden (FVL) and prothrombin G20210A mutations; protein C, protein S and antithrombin activity; factor VIII (FVIII) and von Willebrand factor (vWF), and homocysteine (Hcy) levels. Results: The annual incidence of arterial and venous TE events in our SLE population was 5.4 and 12.4 per 1000, respectively. The highest risk of thrombosis was carried by the simultaneous presence of lupus anticoagulant (LA) and anti‐cardiolipin (aCL) [relative risk (RR) = 4.03, 95% confidence interval (CI) 2.06–7.86] or anti‐β2‐glycoprotein I antibodies (aβ2‐GPI) (RR = 5.10, 95% CI 2.58–10.1). Positivity for the individual aPL tests all carried an elevated TE risk. The presence of other risk factors seemed to be of less importance. Conclusions: In SLE patients, the presence of aPL is a more significant risk factor for the development of thrombosis than the known inherited deficiencies. Based on these data, routine screening for additional hereditary risk factors seems to be unwarranted.
Schistosoma mansoni egg antigens induce Treg that participate in diabetes prevention in NOD mice

Schistosoma mansoni soluble egg antigens (SEA) profoundly regulate the infected host's immune system. We previously showed that SEA prevents type 1 diabetes in NOD mice and that splenocytes from SEA‐treated mice have reduced ability to transfer diabetes to NOD.scid recipients. To further characterize the mechanism of diabetes prevention we examined the cell types involved and showed that CD25+ T‐cell depletion of splenocytes from SEA‐treated donors restored their ability to transfer diabetes. Furthermore, SEA treatment increased the number and proportional representation of Foxp3+ T cells in the pancreas of NOD mice. We have used in vitro systems to analyze the effect of SEA on the development of NOD Foxp3+ T cells. We find that SEA can induce Foxp3 expression in naïve T cells in a TGF‐β‐dependent manner. Foxp3 induction requires the presence of DC, which we also show are modified by SEA to upregulate C‐type lectins, IL‐10 and IL‐2. Our studies show that SEA can have a direct effect on CD4+ T cells increasing expression of TGF‐β, integrin β8 and galectins. These effects of SEA on DC and T cells may act in synergy to induce Foxp3+ Treg in the NOD mouse.
Population pharmacokinetics of piperaquine in adults and children with uncomplicated falciparum or vivax malaria.

AIMS To study the population pharmacokinetics of piperaquine after co-administration with dihydroartemisinin in uncomplicated malaria. METHODS The disposition of piperaquine was studied in 85 Cambodian patients with uncomplicated falciparum or vivax malaria treated with the piperaquine-dihydroartemisinin coformulation Artekin. All patients were given Artekin orally at 0, 6, 24 and 32 h with a total piperaquine dose of 32-35 mg base kg-1. Adults were given tablets while children received either tablets or a dispersible granule formulation. Patients underwent either intensive (17-19 samples) or sparse (2-5 samples) blood sampling schedules over 35 days and clinical/parasitological follow-up over > 28 days. Piperaquine in plasma was quantified by high performance liquid chromatography. RESULTS All patients achieved fever clearance within 24 h and parasite clearance within 72 h. The 28-day cure rate was 97% in adults and 98% in children. A covariate-free two-compartment population model with first-order absorption and elimination gave the most robust representation of the plasma concentration-time data in both adults and children. In adults (n = 38), the median (interquartile range) derived pharmacokinetic descriptors CL/F, Vss/F and t1/2,z were 0.9 l h-1 kg-1 (0.79-1.02 l h-1 kg-1), 574 l kg-1(371-711 l kg-1) and 23 days (19-28 days), respectively. In children (n = 47), corresponding values were 1.8 l h-1 kg-1 (1.29-2.3 l h-1 kg-1), 614 l kg-1 (332-1205 l kg-1) and 14 days (10-18 days), respectively. CONCLUSIONS Piperaquine is a highly lipid-soluble drug with a large Vss/F, long t1/2,z and a clearance that is markedly higher in children than in adults.
The Evolutionary Conserved Oil Body Associated Protein OBAP1 Participates in the Regulation of Oil Body Size1[W][OPEN]

A new family of oil body associated proteins present in plants, fungi, and bacteria are involved in determining oil body size and shape. A transcriptomic approach has been used to identify genes predominantly expressed in maize (Zea mays) scutellum during maturation. One of the identified genes is oil body associated protein1 (obap1), which is transcribed during seed maturation predominantly in the scutellum, and its expression decreases rapidly after germination. Proteins similar to OBAP1 are present in all plants, including primitive plants and mosses, and in some fungi and bacteria. In plants, obap genes are divided in two subfamilies. Arabidopsis (Arabidopsis thaliana) genome contains five genes coding for OBAP proteins. Arabidopsis OBAP1a protein is accumulated during seed maturation and disappears after germination. Agroinfiltration of tobacco (Nicotiana benthamiana) epidermal leaf cells with fusions of OBAP1 to yellow fluorescent protein and immunogold labeling of embryo transmission electron microscopy sections showed that OBAP1 protein is mainly localized in the surface of the oil bodies. OBAP1 protein was detected in the oil body cellular fraction of Arabidopsis embryos. Deletion analyses demonstrate that the most hydrophilic part of the protein is responsible for the oil body localization, which suggests an indirect interaction of OBAP1 with other proteins in the oil body surface. An Arabidopsis mutant with a transfer DNA inserted in the second exon of the obap1a gene and an RNA interference line against the same gene showed a decrease in the germination rate, a decrease in seed oil content, and changes in fatty acid composition, and their embryos have few, big, and irregular oil bodies compared with the wild type. Taken together, our findings suggest that OBAP1 protein is involved in the stability of oil bodies.
Expression of E-cadherin, alpha-catenin and beta-catenin in normal ovarian surface epithelium and epithelial ovarian cancers.

AIMS To study the expression of the epithelial adhesion molecule E-cadherin and its associated proteins alpha and beta catenin in paraffin sections of normal ovaries, benign cystadenomas and ovarian carcinomas, and in immortalized normal ovarian surface epithelial cells and ovarian carcinoma cells in culture. METHODS AND RESULTS Immunocytochemistry was used to study expression of the proteins in paraffin sections and western blotting was used to determine levels of expression of the proteins in cell extracts. E-cadherin expression was found to be absent in ovarian surface epithelial cells in culture and infrequently expressed in normal ovarian surface epithelial cells in vivo, although apical punctate staining was occasionally seen. Seven of nine benign cystadenomas and 29/34 epithelial ovarian carcinomas showed some expression of E-cadherin, but expression was absent in poorly differentiated tumours. Expression of alpha and beta catenin was consistently detected on the lateral membranes of normal ovarian epithelium and benign cystadenomas. alpha and beta catenin expression was lost in 18% and 21% of ovarian carcinomas, respectively: other ovarian carcinomas expressed these proteins at a reduced level. A small number of these tumours showed a diffuse cytoplasmic rather than membranous staining. Reduced staining for alpha and beta catenin appeared to correlate with a more spindly, less adhesive morphology and increased invasive potential in matrigel. CONCLUSIONS The results suggest that E-cadherin expression is generally induced in well differentiated ovarian cancers. In contrast, alpha and beta catenins are consistently expressed in the normal ovarian surface epithelium and benign tumours, but are sometimes reduced or absent in ovarian carcinomas. It is likely that the catenins associate with membrane proteins other than E-cadherin in ovarian epithelium, and they may possibly function as tumour suppressors in this epithelium.
ARE PUBLIC PENSIONS KEEPING UP WITH THE TIMES

etirement plans for public employees in the United States face serious challenges. These pension plans are increasingly costly, underfunded, and create incentives that undermine the recruitment and retention of the most talented public servants. Out-of-control pension costs have played a role in the high-profile bankruptcies of cities around The costs of pension plans have steadily increased even as governments' ability to pay them has been decimated by the weak economy. Over the decade between 2001 and 2011, state and local government contributions to employee retirement systems nearly doubled in constant dollars, reaching a total of $96 billion. Since 2007, these contributions have increased every year and have consumed an increasingly large share of total government spending. The true rise in costs is much greater than these numbers indicate because public pension plans are increasingly underfunded. The underfunding problem has two key components. First, by their own calculations, most states are not contributing enough to keep up with the pension promises they are making to their employees. Some states are setting aside far less than they need to meet their obligations, thereby pushing the cost onto future taxpayers. At the bottom of the list are New Jersey and Pennsylvania, which made less than one-third of their required contributions in 2010. Second, states' calculations seriously understate the extent of the funding problem. Most states assume that they will earn an average rate of return of 8 percent a year on their pension funds, a highly unlikely outcome in the current economic environment. This unrealistic assumption still produces a staggering unfunded liability: $0.9 trillion in 2011. Using a more reasonable assumption of a 5 percent return increases the unfunded liability to $2.7 trillion, which implies that the average state has only funded half of its pension promises. A funding gap of $2.7 2 trillion is more than four times the $607 billion in general outstanding debt on states' books in 2012. The result of years of underfunding and less-than-expected investment performance is that some states have far too little money set aside to fund their pension systems. Even by their own misleading calculations, many states have set aside less than two thirds of what they need to meet their pension obligations. In 2010, the state pension plans in Rhode Island, and West Virginia were less than 60 percent funded. Using more accurate accounting techniques would surely show these states to be in even …
The Use of Antibody to Complement Protein C5 for Salvage Treatment of Severe Antibody‐Mediated Rejection

Desensitized patients are at high risk of developing acute antibody‐mediated rejection (AMR). In most cases, the rejection episodes are mild and respond to a short course of plasmapheresis (PP) / low‐dose IVIg treatment. However, a subset of patients experience severe AMR associated with sudden onset oliguria. We previously described the utility of emergent splenectomy in rescuing allografts in patients with this type of severe AMR. However, not all patients are good candidates for splenectomy. Here we present a single case in which eculizumab, a complement protein C5 antibody that inhibits the formation of the membrane attack complex (MAC), was used combined with PP/IVIg to salvage a kidney undergoing severe AMR. We show a marked decrease in C5b‐C9 (MAC) complex deposition in the kidney after the administration of eculizumab.
Randomized Controlled Study to Evaluate the Efficacy of Adalimumab in Patients with Different Forms of Refractory Uveitis

ABSTRACT Purpose: TNF alpha inhibitors have revolutionized the care of vision-threatening uveitis. This study evaluated the efficacy of adalimumab (ADA) for the treatment of refractory noninfectious uveitis. Design: Randomized, prospective, controlled, two-center clinical trial Methods: Patients with active uveitis despite combined oral low-dose prednisolone and immunosuppression were randomized for additional ADA with corticosteroids in a fixed tapering regime, or corticosteroids only. Primary outcome measure at three months was improved best-corrected visual acuity (BCVA; >2 lines). In case of treatment failure, switch to the other arm was possible. Results: Twenty-five patients (10 ADA, 15 controls) were included. BCVA increased with ADA by > 2 lines in 6/10 patients (60%; mean increase of 0.23 logMAR), but in only 2/15 from controls (13%, mean increase of 0.04 logMAR, Fisher´s exact test p = 0.00221). Conclusions: The results show superiority of ADA over controls in severe ocular inflammation including anterior uveitis.
Pharmacological properties of a novel gastrointestinal prokinetic benzamide selective for human 5-HT4 receptor versus human 5-HT3 receptor.

Binding properties of gastrointestinal prokinetic benzamides for both cloned human 5-hydroxytryptamine (5-HT)3 receptors and cloned human 5-HT4 receptors were examined and pharmacological properties of YM-53389{(+)-(S)-2-chloro-5-methoxy-4-[5-(2-piperidylmethyl)-1,2, 4-oxadiazol-3-yl]aniline monohydrochloride} were characterised in animals. Cisapride, renzapride and zacopride inhibited specific binding of [3H]ramosetron to cloned human 5-HT3 receptors, with Ki values of 684, 7.64 and 0.38 n m, respectively. YM-53389, however, slightly replaced that (Ki>10,000 n m). YM-53389, cisapride, renzapride and zacopride replaced specific binding of [3H]GR 113808 to cloned human 5-HT4 receptors, with Ki values of 54.6, 41.5, 115 and 373 n m, respectively. The potency for inhibitory effect of YM-53389 on 5-HT3 receptor-mediated contraction in the guinea-pig isolated colon was very low with pIC50 of 4.7. YM-53389 exerted 5-HT4 receptor-mediated relaxation in the carbachol-precontracted rat isolated oesophagus with pEC50 of 6.3. In mice, YM-53389 at 10 and 30 mg kg-1, s.c. significantly shortened whole gut transit time, in contrast to cisapride, renzapride and zacopride which were reported to delay that. YM-53389 had no significant effect on upper gastrointestinal propulsion at doses up to 30 mg kg-1, s.c. Based on these results, YM-53389 may surpass existing benzamides in facilitating lower intestinal propulsion and benefit patients with gastrointestinal disorders associated with impair of intestinal propulsion, such as constipation, based on the selective interaction with human 5-HT4 receptors vs human 5-HT3 receptors.
α‐Actin isoform distribution in normal and failing human heart: a morphological, morphometric, and biochemical study

We investigated the distribution of α‐skeletal, α‐cardiac, and α‐smooth muscle actin isoforms in human heart during development, hypertrophy, and failure. At 20 weeks of fetal life, α‐skeletal actin was localized in a small proportion of subendocardial and papillary muscle cardiomyocytes. At this gestation time, diffuse α‐cardiac actin staining was observed, associated with focal expression of α‐smooth muscle actin. In normal adult subjects, α‐skeletal actin positive cardiomyocytes were distributed in a transmural gradient with the highest proportion located subendocardially. In myocardial hypertrophy and cardiomyopathies, the amount of α‐skeletal actin was increased and diffuse staining was seen in all layers of ventricular myocardium, with the exception of idiopathic dilated cardiomyopathies. Cardiomyocytes were negative for α‐smooth muscle actin in all pathological situations studied. As expected, fibroblasts in post‐infarct scars expressed α‐smooth muscle actin and transforming growth factor‐β1 but, surprisingly, were negative for these proteins in interstitial fibrosis. Our results demonstrate that increased expression of α‐skeletal actin in the diseased human heart is associated with increased myocyte stretch, increased wall stress, and pressure overload, but not with idiopathic dilated cardiomyopathies. They also suggest that fibrotic changes develop with different mechanisms in scars versus interstitial fibrosis. Copyright © 2003 John Wiley & Sons, Ltd.
Does theatre improve the quality of life of people with dementia?

ABSTRACT Background: A new communication method, the “Veder method”, has recently been developed. Caregivers are trained to apply this method in a group activity (“living-room theatre activity”) for people with dementia in which theatrical stimuli are used in combination with proven emotion-oriented care methods. The aim of this exploratory study was to evaluate the added value of the Veder method group activity compared to a regular reminiscence group activity and to investigate whether professional carers can achieve the same effects with the Veder method as professional actors. Methods: A quasi-experimental three-group design was used. Experimental group 1 (E1; n = 65) joined a living-room theatre activity offered by trained professional caregivers. Experimental group 2 (E2; n = 31) joined a living-room theatre activity offered by professional actors. The control group (n = 55) received a usual reminiscence group activity. Behavior, mood and aspects of quality of life were measured using standardized observation scales at three points in time: (T1) pretest; (T2) during the intervention and; (T3) post-test, two hours after the intervention. Results: During the intervention, significant differences were found in favor of the group that was offered a living-room theatre activity by actors (E2) on different aspects of behavior, mood and quality of life. At post-test, people in E2 were more alert compared to the control group. Moreover, they recalled more memories and showed less socially isolated behavior compared to the control group. Conclusion: This exploratory study shows that the Veder method has some clear positive effects on behavior and mood of people with dementia when applied by professional actors.