Alternatives to Guardianship and Conservatorship for Adults in Iowa, Revised 2007

Independence, respect, and equality are values important to all people. These values help define the concepts of autonomy (independence and freedom) and self-determination (the right to make decisions for one’s self). Because these rights are so valued in our society and are something that most of us would value for ourselves, the “least restrictive alternative” should always be considered before taking away a person’s civil and legal rights to make decisions for him or herself. The least restrictive alternative is an option, which allows a person to keep as much autonomy, and self-determination as possible while providing only the level of protection and supervision that is necessary. Some examples may include: representative payee for certain government benefit checks, joint bank accounts or advance directives for health care.

Diagnostic contribution of cardiac magnetic resonance in patients with acute coronary syndrome and culprit-free angiograms.

BACKGROUND: In spite of robust knowledge about underlying ischemic myocardial damage, acute coronary syndromes (ACS) with culprit-free angiograms raise diagnostic concerns. The present study aimed to evaluate the additional value of cardiac magnetic resonance (CMR) over commonly available non-CMR standard tests, for the differentiation of myocardial injury in patients with ACS and non-obstructed coronary arteries. MATERIAL/METHODS: Patients with ACS, elevated hs-TnT, and a culprit-free angiogram were prospectively enrolled into the study between January 2009 and July 2013. After initial evaluation with standard tests (ECG, echocardiography, hs-TnT) and provisional exclusion of acute myocardial infarction (AMI) in coronary angiogram, patients were referred for CMR with the suspicion of myocarditis or Takotsubo cardiomyopathy (TTC). According to the result of CMR, patients were reclassified as having myocarditis, AMI, TTC, or non-injured myocardium as assessed by late gadolinium enhancement. RESULTS: Out of 5110 patients admitted with ACS, 75 had normal coronary angiograms and entered the study; 69 of them (92%) were suspected for myocarditis and 6 (8%) for TTC. After CMR, 49 patients were finally diagnosed with myocarditis (65%), 3 with TTC (4%), 7 with AMI (9%), and 16 (21%) with non-injured myocardium. The provisional diagnosis was changed or excluded in 23 patients (31%), with a 9% rate of unrecognized AMI. CONCLUSIONS: The study results suggest that the evaluation of patients with ACS and culprit-free angiogram should be complemented by a CMR examination, if available, because the initial work-up with non-CMR tests leads to a significant proportion of misdiagnosed AMI.

Complexin I regulates glucose-induced secretion in pancreatic beta-cells.

The neuronal-specific protein complexin I (CPX I) plays an important role in controlling the Ca(2+)-dependent neurotransmitter release. Since insulin exocytosis and neurotransmitter release rely on similar molecular mechanisms and that pancreatic beta-cells and neuronal cells share the expression of many restricted genes, we investigated the potential role of CPX I in insulin-secreting cells. We found that pancreatic islets and several insulin-secreting cell lines express high levels of CPX I. The beta-cell expression of CPX I is mediated by the presence of a neuron restrictive silencer element located within the regulatory region of the gene. This element bound the transcriptional repressor REST, which is found in most cell types with the exception of mature neuronal cells and beta-cells. Overexpression of CPX I or silencing of the CPX I gene (Cplx1) by RNA interference led to strong impairment in beta-cell secretion in response to nutrients such as glucose, leucine and KCl. This effect was detected both in the early and the sustained secretory phases but was much more pronounced in the early phase. We conclude that CPX I plays a critical role in beta-cells in the control of the stimulated-exocytosis of insulin.

Perinuclear Mlp proteins down-regulate gene expression in response to a defect in mRNA export

Résumé Une caractéristique des cellules eucaryotes est le confinement du matériel génétique (ADN/DNA) dans le noyau. Pour décoder cette information, un ARN messager (mRNA) est d'abord transcrit sous forme d'un ARN prémessager (pré-mRNA). Ce-dernier doit subir plusieurs étapes de maturation pour aboutir à une particule ribonucléoprotéique (mRNP) qui sera exportée vers le cytoplasme et traduite en protéine. La protéine de levure Mex67p et son homologue humain TAP sont des récepteurs d'export médiant la translocation du mRNP au travers des complexes du pore nucléaire (NPC). Mex67p/TAP ne se lient pas directement au mRNA, mais nécessitent la présence de protéines adaptatrices, telles que Yra1p et son homologue humain REF1. Afin d'identifier de nouveaux facteurs impliqués dans l'export des mRNPs ou de nouvelles fonctions pour Yra1p, nous avons effectué un crible génétique avec un mutant thermosensible de Yra1p, GFP-yra 1 -8. Ce mutant présente un défaut d'export des mRNAs et une diminution des niveaux de transcrits du gène rapporteur LacZ ainsi que de certains transcrits endogènes. Nous avons trouvé que la perte de Mlp2p, ou d'une protéine hautement similaire, Mlp1p, restaure la croissance du mutant GFP-yra1-8 à température restrictive. Mlp1p et Mlp2p sont des protéines nucléaires, dont l'homologue humain est TPR. Les Mlp (myosin¬like proteins) ainsi que TPR forment des structures filamenteuses ancrées aux NPC. Bien que la fonction des Mlp ne soit pas clairement définie, un rôle dans la biogenèse et la surveillance des mRNPs a été récemment proposé. Notre étude montre que la perte des Mlp, non seulement restaure la croissance de GFP-yra1-8, mais augmente aussi les niveaux des transcrits LacZ et facilite leur apparition dans le cytoplasme. Des expériences d'immunoprécipitations de la chromatine révèlent que Mlp2p diminue le taux de synthèse du transcrit LacZ dans GFP-yra1-8. Des analyses du transcriptome montrent que Mlp2p réduit aussi les niveaux d'une population de transcrits endogènes dans le mutant. Finalement, des localisations in situ suggèrent que la transcription du rapporteur LacZ a lieu à la périphérie du noyau, à proximité des Mlp. Ainsi, les protéines Mlp pourraient préférentiellement diminuer la transcription de gènes exprimés à la périphérie nucléaire. Nous montrons aussi que Yra1p interagit génétiquement avec Nab2p une protéine liée au mRNA et impliquée dans son export, mais non avec d'autres protéines également impliquées dans l'export des mRNAs. Les résultats obtenus soutiennent un modèle où les protéines Yra1p et Nab2p sont nécessaires à l'arrimage des mRNPs sur la plate-forme des Mlp. Si ces signaux manquent ou sont défectueux, les mRNPs ne peuvent pas poursuivre leur trajet vers le canal central du NPC. Ce bloc induirait par la suite une diminution de la transcription d'une population de gènes potentiellement localisée à la périphérie nucléaire. Dans son ensemble, cette étude suggère que les protéines Mlp établissent un lien entre la transcription de certains mRNAs et leur export au travers du pore nucléaire. Summary A hallmark of the eukaryotic cell is the packaging of DNA in the nucleus. To decode the genetic information, a messenger RNA (mRNA) is first synthesized as a pre-mRNA molecule, which undergoes different maturation steps resulting in an mRNP (messenger RNA ribonucleoprotein), which can be actively transported to the cytoplasm and translated into a protein. Yeast Mex67p and its human homologue TAP are export receptors mediating mRNP translocation through the nuclear pore complex (NPC). The recruitment of Mex67p/TAP to mRNA is mediated by mRNA export adaptors of the evolutionarily conserved REF (RNA and Export Factor binding) family: yeast Yra1p and human REF1. To uncover new functions of Yra1p or new factors implicated in mRNA export, we performed a genetic screen with a themiosensitive (ts) yra1 mutant, GFP-yra1-8. This mutant exhibits mRNA export defects and a decrease in the levels of LacZ reporter and certain endogenous transcripts. We found that the loss of Mlp2p, or the related Mlp1p protein, substantially rescues the growth defect of the GFP-yra1 -8 mutant. Mlp1p and M1p2p are large non-essential proteins, homologous to human TPR, proposed to form intra-nuclear filamentous structures anchored at the NPC. Their role is not clearly defined, but they have been implicated in mRNP biogenesis and surveillance. Our study shows that loss of Mlp proteins not only restores growth of GFP-yra1-8, but also rescues LacZ mRNA levels and increases their appearance in the cytoplasm. Chromatin immunoprecipitation and pulse chase experiments indicate that Mlp2p down-regulates LacZ mRNA synthesis in GFP-yra1-8. DNA micro- array analyses reveal that Mlp2p also reduces the levels of a subset of cellular transcripts in the yra1 mutant strain. In situ localizations suggest that LacZ transcription occurs at the nuclear periphery, in close proximity to Mlp proteins. Thus, Mlp proteins may preferentially down-regulate genes expressed at the nuclear periphery. Finally, we show that Yra1p genetically interacts with the shuttling mRNA-binding protein Nab2p and that loss of Mlp proteins rescues the growth defect of yra1 and nab2, but not other mRNA export mutants. The data support a model in which Nab2p and Yra1p are required for rnRNP docking to the Mlp platform. Lack of these signals prevents mRNPs from crossing the Mlp gate. This block may then negatively feed-back on the transcription of a subset of genes, potentially located at the nuclear envelope. Overall, this study suggests that perinuclear Mlp proteins establish a link between mRNA transcription and export.

Caste determination through mating in primitively eusocial societies.

Eusocial animal societies are typified by the presence of a helper (worker) caste which predominantly cares for young offspring in a social group while investing little in their own direct reproduction. A key question is what determines whether an individual becomes a worker or leaves to initiate her own reproduction. In some insects, caste is determined nutritionally during development. In others, and in vertebrate societies, adults are totipotent and the cues that determine caste are less well known. The mate limitation hypothesis (MLH) states that a female's mating status acts as a cue for caste determination: females that mate become reproductives, while those that fail to mate become workers. The MLH is consistent with empirical observations in sweat bees showing that over the course of the nesting season, there are increases in both the proportion of females that become reproductives and the frequency of males in the mating pool. We modelled a foundress's offspring sex-ratio strategy to investigate whether an increasingly male-biased operational sex-ratio over time is evolutionarily stable under the MLH. Our results indicate that such a pattern could occur if early workers were more valuable than late workers. This pattern was then more likely if male mortality was high, if worker mortality was low, if the value of a worker was high and if the period over which workers can help was short. Our results suggest that the MLH can be evolutionarily stable, but only under restrictive conditions. Manipulative experiments are now required to investigate whether mating determines caste in nature.

Reconsidering the "policy gap":policy implementation and outcomes in Spain

By analysing entry policies and regularisation procedures in Spain from the 1990s to 2007, this article examines how the mismatch between very restrictive immigration policies and increasing foreign labour demands translated into a model of illegal migration, which in turn gave rise to the need to carry out periodical regularisation drives. This double 'policy gap' between legality and reality, and between entry policies and regularisation procedures, is explained as a policy in itself and as a way to solve in practice the apparently unsolvable dilemma between the demands for closure and the insatiable demands for foreign workers.

Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity.

Overactivation of the sympatho-adrenergic system is an essential mechanism providing short-term adaptation to the stressful conditions of critical illnesses. In the same way, the administration of exogenous catecholamines is mandatory to support the failing circulation in acutely ill patients. In contrast to these short-term benefits, prolonged adrenergic stress is detrimental to the cardiovascular system by initiating a series of adverse effects triggering significant cardiotoxicity, whose pathophysiological mechanisms are complex and only partially elucidated. In addition to the development of myocardial oxygen supply/demand imbalance induced by the sustained activation of adrenergic receptors, catecholamines can damage cardiomyocytes by fostering mitochondrial dysfunction, via two main mechanisms. The first one is calcium overload, consecutive to β-adrenergic receptor-mediated activation of protein kinase A and subsequent phosphorylation of multiple Ca(2+)-cycling proteins. The second one is oxidative stress, primarily related to the transformation of catecholamines into "aminochromes," which undergo redox cycling in mitochondria to generate copious amounts of oxygen-derived free radicals. In turn, calcium overload and oxidative stress promote mitochondrial permeability transition and cardiomyocyte cell death, both via the apoptotic and necrotic pathways. Comparable mechanisms of myocardial toxicity, including marked oxidative stress and mitochondrial dysfunction, have been reported with the use of cocaine, a common recreational drug with potent sympathomimetic activity. The aim of the current review is to present in detail the pathophysiological processes underlying the development of catecholamine and cocaine-induced cardiomyopathy, as such conditions may be frequently encountered in the clinical practice of cardiologists and ICU specialists.

Cardiac raptor deletion impairs adaptive hypertrophy, alters metabolic gene expression and causes heart failure in mice

Background: Mammalian target of rapamycin (mTOR), a central regulator of cell growth, is found in two structurally and functionally distinct multiprotein complexes called mTOR complex (mTORC)1 and mTORC2. The specific roles of each of these branches of mTOR signaling have not been dissected in the adult heart. In the present study, we aimed to bring new insights into the function of cardiac mTORC1-mediated signaling in physiological as well as pathological situations.Methods: We generated mice homozygous for loxP-flanked raptor and positive for the tamoxifen-inducible Cre recombinase (MerCreMer) under control of the α- myosin heavy chain promoter. The raptor gene encodes an essential component of mTORC1. Gene ablation was induced at the age of 10-12 weeks, and two weeks later the raptor cardiac-knockout (raptor-cKO) mice started voluntary cagewheel exercise or were subjected to transverse aortic constriction (TAC) to induce pressure overload.Results: In sedentary raptor-cKO mice, ejection fractions gradually decreased, resulting in significantly reduced values at 38 days (P < 0.001). Raptor-cKO mice started to die during the fifth week after the last tamoxifen injection. At that time, the mortality rate was 36% in sedentary (n = 11) and 64% in exercising (n = 14) mice. TAC-induced pressure overload resulted in severe cardiac dysfunction already at earlier timepoints. Thus, at 7-9 days after surgery, ejection fraction and fractional shortening values were 22.3% vs 43.5% and 10.2% vs 21.5% in raptor-cKO vs wild-type mice, respectively. This was accompanied by significant reductions of ventricular wall and septal thickness as well as an increase in left ventricular internal diameter. Moreover, ventricular weight to tibial length ratios were increased in wild-type, but not in the raptor-cKO TAC mice. Together, this shows that raptor-cKO mice rapidly developed dilated cardiomyopathy without going through a phase of adaptive hypertrophy. Expression of ANP and β-MHC was induced in all raptor-cKO mice irrespective of the cardiac load conditions. Consistent with reduced mTORC1 activity, phosphorylation of ribosomal S6 kinase and 4E-BP1 was blunted, indicating reduced protein synthesis. Moreover, expression of multiple genes involved in the regulation of energy metabolism was altered, and followed by a shift from fatty acid to glucose oxidation.Conclusion: Our study suggests that mTORC1 coordinates protein and energy metabolic pathways in the heart. Moreover, we demonstrate that raptor is essential for the cardiac adaptation to increased workload and importantly, also for normal physiological cardiac function.

Médecine d'urgence [Emergency medicine: updates 2013].

New evidences published this year are susceptible to change the management of several medical emergencies. Combined antiplatelet therapy might be beneficial for the management of TIA or minor stroke and rapid blood pressure lowering might improve the outcome in patients with intracerebral hemorrhage. A restrictive red cell transfusion strategy is indicated in case of upper digestive bleeding and coagulation factors concentrates are superior to fresh frozen plasma for urgent warfarin reversal. Prolonged systemic steroid therapy is not warranted in case of acute exacerbation of BPCO, and iterative physiotherapy is not beneficial after acute whiplash. Finally, family presence during cardiopulmonary resuscitation may reduce post-traumatic stress disorder among relatives.

PPARβ/δ attenuates palmitate-induced endoplasmic reticulum stress and induces autophagic markers in human cardiac cells.

BACKGROUND: Chronic endoplasmic reticulum (ER) stress contributes to the apoptotic cell death in the myocardium, thereby playing a critical role in the development of cardiomyopathy. ER stress has been reported to be induced after high-fat diet feeding in mice and also after saturated fatty acid treatment in vitro. Therefore, since several studies have shown that peroxisome proliferator-activated receptor (PPAR)β/δ inhibits ER stress, the main goal of this study consisted in investigating whether activation of this nuclear receptor was able to prevent lipid-induced ER stress in cardiac cells. METHODS AND RESULTS: Wild-type and transgenic mice with reduced PPARβ/δ expression were fed a standard diet or a high-fat diet for two months. For in vitro studies, a cardiomyocyte cell line of human origin, AC16, was treated with palmitate and the PPARβ/δ agonist GW501516. Our results demonstrate that palmitate induced ER stress in AC16 cells, a fact which was prevented after PPARβ/δ activation with GW501516. Interestingly, the effect of GW501516 on ER stress occurred in an AMPK-independent manner. The most striking result of this study is that GW501516 treatment also upregulated the protein levels of beclin 1 and LC3II, two well-known markers of autophagy. In accordance with this, feeding on a high-fat diet or suppression of PPARβ/δ in knockout mice induced ER stress in the heart. Moreover, PPARβ/δ knockout mice also displayed a reduction in autophagic markers. CONCLUSION: Our data indicate that PPARβ/δ activation might be useful to prevent the harmful effects of ER stress induced by saturated fatty acids in the heart by inducing autophagy.

Field Evaluation of Pavement Marking Materials, MLR-79-02, 1979

Pavement marking materials other than conventional paint must be evaluated as environmental standards become more restrictive. The new EPA classification for solvents states that all oil paints are photochemically reactive and, therefore, contribute to smog. This will eventually result in the elimination of organic solvents from all paints, which may occur in Iowa by 1985. The Special Investigations Section of the Office of Materials field reviewed all urban and rural applications of pavement marking materials in the spring of 1979. The field review consisted of a visual estimation of percent marking missing, percent satisfactory, and percent non-satisfactory; reflective readings by ERMA; and notation of special conditions which may have impacted performance. ERMA was not effective in evaluating the reflective quality of pavement marking materials. No pavement marking materials evaluated have been successful enough to date to totally replace conventional painting methods.

Pathologic ventricular hypertrophy in the offspring of diabetic mothers: a retrospective study.

AIMS: Diabetes in pregnant women is increasing and with that the complications in their offspring. We studied our population of diabetic mothers (2003-2005) for pathologic ventricular hypertrophy (PVH). METHODS AND RESULTS: In our retrospective study of all 87 diabetic pregnancies (92 neonates), 16 were type 1, 17 were type 2, and 54 were gestational diabetes (GD). Haemoglobin glycated (HbA1c) median was 5.8% (5.3-6.5): 17 with HbA1c above normal 2 with congenital heart disease (CHD) and six with PVH. A total of 75 neonates were normal, five had CHD, and 12 had PVH (1/12 died post-natally, 1/12 stillborn, 2/12 required premature delivery, 8/12 normal). The 16 type 1 pregnancies resulted in three neonates with CHD and in 50% PVH, including one death, one premature Cesarean section because of PVH. The 17 neonates of type 2 pregnancies showed in one CHD and in 25% PVH. Of the 54 GD pregnancies, one had CHD and one had PVH. CONCLUSION: Pregnancies of both type 1 and 2 diabetes carry an increased risk for foetal development of PVH compared with those with GD. The insufficient effect of preventive glycaemia controls leads to conclude that although no definite predictive parameters for malignant outcome can be presented, close monitoring of these pregnancies may prevent perinatal catastrophes.

Residuelle Lungenfunktionsveränderungen nach "Adult Respiratory Distress Syndrome" (ARDS) bei Kindern [Residual lung function changes following adult respiratory distress syndrome (ARDS) in children]

Residual lung function abnormalities have been investigated in 9 children (4 boys and 5 girls) a mean 2.7 years after surviving severe adult respiratory distress syndrome (ARDS). All patients had been artificially ventilated for an average of 9.4 days with a FiO2 greater than 0.5 for 34 hours and maximal PEEP levels in the range of 8-20 cm H2O. Since the ARDS, 3 children had presented recurrent respiratory symptoms (moderate exertional dyspnea and cough) and 2 had had evidence of fibrosis on chest radiographs. In all patients abnormal lung functions were found, i.e. ventilation inequalities (8), hypoxemia (7), and obstructive (2) and restrictive (1) lung disease. A significant correlation between respirator therapy and residual lung function was found (duration of FiO2 greater than 0.5 in hours and inspiratory plateau pressure during respirator therapy vs. ventilation inequalities and hypoxemia).

Quantification of Myocardial Perfusion Using 13N-ammonia PET: a Cross-Comparison Study on Analysis Software Packages - Carimas, PMOD and FlowQuant

Aim. Several software packages (SWP) and models have been released for quantification of myocardial perfusion (MP). Although they all are validated against something, the question remains how well their values agree. The present analysis focused on cross-comparison of three SWP for MP quantification of 13N-ammonia PET studies. Materials & Methods. 48 rest and stress MP 13N-ammonia PET studies of hypertrophic cardiomyopathy (HCM) patients (Sciagrà et al., 2009) were analysed with three SW packages - Carimas, PMOD, and FlowQuant - by three observers blinded to the results of each other. All SWP implement the one-tissue-compartment model (1TCM, DeGrado et al. 1996), and first two - the two-tissue-compartment model (2TCM, Hutchins et al. 1990) as well. Linear mixed model for the repeated measures was fitted to the data. Where appropriate we used Bland-Altman plots as well. The reproducibility was assessed on global, regional and segmental levels. Intraclass correlation coefficients (ICC), differences between the SWPs and between models were obtained. ICC≥0.75 indicated excellent reproducibility, 0.4≤ICC<0.75 indicated fair to good reproducibility, ICC<0.4 - poor reproducibility (Rosner, 2010). Results. When 1TCM MP values were compared, the SW agreement on global and regional levels was excellent, except for Carimas vs. PMOD at RCA: ICC=0.715 and for PMOD vs. FlowQuant at LCX:ICC=0.745 which were good. In segmental analysis in five segments: 7,12,13, 16, and 17 the agreement between all SWP was excellent; in the remaining 12 segments the agreement varied between the compared SWP. Carimas showed excellent agreement with FlowQuant in 13 segments and good in four - 1, 5, 6, 11: 0.687≤ICCs≤0.73; Carimas had excellent agreement with PMOD in 11 segments, good in five_4, 9, 10, 14, 15: 0.682≤ICCs≤0.737, and poor in segment 3: ICC=0.341. PMOD had excellent agreement with FlowQuant in eight segments and substantial-to-good in nine_1, 2, 3, 5, 6,8-11: 0.585≤ICCs≤0.738. Agreement between Carimas and PMOD for 2TCM was good at a global level: ICC=0.745, excellent at LCX (0.780) and RCA (0.774), good at LAD (0.662); agreement was excellent for ten segments, fair-to-substantial for segments 2, 3, 8, 14, 15 (0.431≤ICCs≤0.681), poor for segments 4 (0.384) and 17 (0.278). Conclusions. The three SWP used by different operators to analyse 13N-ammonia PET MP studies provide results that agree well at a global level, regional levels, and mostly well even at a segmental level. Agreement is better for 1TCM. Poor agreement at segments 4 and 17 for 2TCM needs further clarification.

Dysfonction microvasculaire et ischémie du myocarde [Microvascular dysfunction and myocardial ischemia]

Une lésion fonctionnelle ou structurale des artérioles intramurales influence le seuil ischémique du myocarde. Le diagnostic de dysfonction microvasculaire est retenu en présence d'une diminution du flux coronaire maximal et de coronaires angio-graphiquement normales ou presque normales. Un trouble de la microcirculation peut traduire une dysfonction endothéliale chez le sujet diabétique ou hyperlipidémique, ou une lésion structurale ou fonctionnelle dans le cadre de la cardiomyopathie hypertrophique, la sténose aortique ou l'hypertension artérielle. Après recanalisation de l'artère responsable d'un infarctus, la mesure de la fonction microcirculatoire permet d'estimer la qualité de la reperfusion myocardique. L'appréciation de la fonction microvasculaire est un enjeu majeur dans l'évaluation de l'ischémie du myocarde en l'absence de sténose coronaire. Functional or structural lesions in intramural arterioles influence the ischemic threshold of the myocardium. Microvascular dysfonction is evidenced by a decrease in coronary blood flow during maximum hyperemia in the presence of angiographically normal or near-normal coronary arteries. Microvascular dysfonction may reflect endothelial dysfonction in diabetic or hyperlipidemic patients, as well as structural and functional changes in patients with hypertrophic cardiomyopathy, aortic stenosis or hypertension. Assessing microvascular fonction after thrombolysis or primary angioplasty for acute myocardial infarction allows to estimate the quality of myocardial reperfusion. Assessing microvascular fonction is a major component of the evaluation of myocardial ischemia in the absence of coronary artery stenoses.