Intrapericardial Ranolazine Prolongs Atrial Refractory Period and Markedly Reduces Atrial Fibrillation Inducibility in the Intact Porcine Heart

Introduction: Extensive experimental studies and clinical evidence (Metabolic Efficiency with Ranzolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction-36 [MERLIN TIMI-36] trial) indicate potential antiarrhythmic efficacy of the antianginal agent ranolazine. Delivery of agents into the pericardial space allows high local concentrations to be maintained in close proximity to myocardial tissue while systemic effects are minimized. Methods and Results: The effects of intrapericardial (IPC) administration of ranolazine (50-mg bolus) on right atrial and right ventricular effective refractory periods (ERP), atrial fibrillation threshold, and ventricular fibrillation threshold were determined in 17 closed-chest anesthetized pigs. IPC ranolazine increased atrial ERP in a time-dependent manner from 129 +/- 5.14 to 186 +/- 9.78 ms (P < 0.01, N = 7) but did not significantly affect ventricular ERP (from 188.3 +/- 4.6 to 201 +/- 4.3 ms (NS, N = 6). IPC ranolazine increased atrial fibrillation threshold from 4.8 +/- 0.8 to 28 +/- 2.3 mA (P < 0.03, N = 6) and ventricular fibrillation threshold (from 24 +/- 3.56 baseline to 29.33 +/- 2.04 mA at 10-20 minutes, P < 0.03, N = 6). No significant change in mean arterial pressure was observed (from 92.8 +/- 7.1 to 74.8 +/- 7.5 mm Hg, P < 0.125, N = 5, at 7 minutes). Conclusions: IPC ranolazine exhibits striking atrial antiarrhythmic actions as evidenced by increases in refractoriness and in fibrillation inducibility without significantly altering mean arterial blood pressure. Ranolazine`s effects on the atria appear to be more potent than those on the ventricles.

Abnormal methylation at the KvDMR1 imprinting control region in clinically normal children conceived by assisted reproductive technologies

Genomic imprinting alterations have been shown to be associated with assisted reproductive technologies (ARTs) in animals. At present, data obtained in humans are inconclusive; however, some epidemiological studies have demonstrated an increased incidence of imprinting disorders in children conceived by ARTs. In the present study, we focused on the effect of ARTs [IVF and intracytoplasmic sperm injection (ICSI)] on the epigenetic reprogramming of the maternally methylated imprinting control region KvDMR1 in clinically normal children. Qualitative and quantitative methylation at KvDMR1 were assessed by the methylation-specific PCR approach and by the methylation-sensitive enzymatic digestion associated with real-time PCR method, respectively. DNA was obtained from peripheral blood of 12/18 and umbilical cord blood and placenta of 6/18 children conceived by IVF or ICSI. The methylation patterns observed in this group were compared with the patterns observed in 30 clinically normal naturally conceived children (negative controls) and in 3 naturally conceived Beckwith-Wiedemann syndrome patients (positive controls). Hypomethylation at KvDMR1 was observed in 3/18 clinically normal children conceived by ARTs (2 conceived by IVF and 1 by ICSI). A discordant methylation pattern was observed in the three corresponding dizygotic twins. Our findings corroborate the hypothesis of vulnerability of maternal imprinting to ARTs. Furthermore, the discordant methylation at KvDMR1 observed between dizygotic twins could be consequent to one of the following possibilities: (i) a differential vulnerability of maternal imprints among different embryos; or (ii) epimutations that occurred during gametogenesis resulting in the production of oocytes without the correct primary imprint at KvDMR1.

Gastrointestinal transit, appetite, and energy balance in gastrectomized patients

Background: Alterations in gastrointestinal tract physiology after gastrectomy may affect appetite and energy balance. Objective: The objective of this study was to examine energy balance, appetite, and gastrointestinal transit in subjects with gastrectomy. Design: Seven subjects with total gastrectomy (TG) and 14 subjects with partial gastrectomy (PG), who were free from signs of recurrent disease, and 10 healthy control subjects were studied. Resting energy expenditure (REE) was measured by indirect calorimetry and compared with REE predicted by the Harris-Benedict equation (mREE/pREE%). Gastrointestinal transit was measured by scintigraphy. Habitual food intake was assessed, and appetite was measured during scintigraphy after ingestion of a test meal (361 kcal). Results: Body mass index was not different among the groups. mREE/pREE% was higher in patients with PG (P < 0.01) than in control subjects. The TG group showed higher energy intake (P < 0.05) than the PG group and control subjects. Gastric emptying was faster in the PG group than in control subjects, and gastrointestinal transit was accelerated in both PG and TG groups. An intense, precocious postprandial fullness and a relatively early recovery of hunger and prospective consumption sensations were seen in these patients. Conclusions: Patients with PG or TG have higher than predicted energy expenditure, which in TG seems to be compensated for by increased energy intake. These patients have preserved postprandial appetite responses and precocious postprandial fullness, which seem to be associated with disturbances in gastrointestinal transit of the ingested meal and are likely to be independent of vagal fiber integrity or stomach-released ghrelin. Am J Clin Nutr 2009; 89: 231-9.

Ghrelin and PYY(3-36) in gastrectomized and vagotomized patients: relations with appetite, energy intake and resting energy expenditure

Background/Objectives: Reduced food intake, appetite loss and alteration of ghrelin and PYY(3-36) secretion have been suggested to have a function in the loss of body weight commonly observed after gastrectomy. The objective of this study was to investigate the circulating concentrations of ghrelin and PYY(3-36) and their relationships with food intake, appetite and resting energy expenditure (REE) after gastrectomy plus vagotomy. Subjects/Methods: Seven patients with total gastrectomy (TG), 14 with partial gastrectomy (PG) and 10 healthy controls were studied. Habitual food intake and REE was assessed; fasting and postprandial plasma total ghrelin, PYY(3-36) concentrations and appetite ratings were determined after ingestion of a liquid test meal. Results: Differently from PG and controls, fasting ghrelin correlated with REE, and a higher energy intake was observed in the TG group. Fasting plasma ghrelin concentrations were lower in TG compared with controls, and no ghrelin response to the meal was observed in either PG or TG. Fasting plasma PYY(3-36) concentrations were not different among the groups. There was an early and exaggerated postprandial rise in PYY(3-36) levels in both PG and TG groups, but not in controls. No effect of ghrelin or PYY(3-36) concentrations was observed on hunger, prospective consumption or fullness ratings. Conclusions: Total ghrelin and PYY(3-36) do not seem to be involved with appetite or energy intake regulation after gastrectomy plus vagotomy. Ghrelin secreted by sources other than stomach is likely to have a function in the long-term regulation of body weight after TG. European Journal of Clinical Nutrition (2010) 64, 845-852; doi: 10.1038/ejcn.2010.88; published online 19 May 2010

Hospitalizations for HIV/AIDS: Differences Between Sexes

Background: Women are especially vulnerable to HIV infection because of biological, social, cultural, and economic factors. In Brazil, AIDS was initially seen predominantly in homosexual men, but the epidemic gradually reached a gender balance as increasing numbers of women became infected with HIV. Objective: The aim of the present study was to identify the clinical and epidemiologic characteristics of hospitalized patients with HIV/AIDS of both sexes and compare the differences between them. Methods: This epidemiologic cross-sectional study evaluated gender differences in demographic, social, clinical, and epidemiologic characteristics of patients diagnosed with HIV/AIDS who were admitted for any reason to the Public Hospital of the Medical School of the Federal University of Triangulo Mineiro, Uberaba, Minas Gerais State, Brazil. Results: A total of 363 patients were included in the analysis, with a male/female ratio of 1.1:1.0. Forty-one percent of women were pregnant. Mean age at hospitalization and duration of hospitalization were significantly greater among men (P < 0.05). Men and nonpregnant women were admitted because of infection significantly more often than were pregnant women (P < 0.05). Significantly more single men who reported homosexual, bisexual, or heterosexual behavior associated with drug use were admitted compared with women (P < 0.05). Women admitted for treatment were significantly more likely than men to be employed (P < 0.05). Adherence to antiretroviral treatment and T CD4+ lymphocyte count indicated important differences between the sexes, with better parameters observed among nonpregnant and pregnant women compared with men. Conclusions: In the present study, women with HIV/AIDS who were admitted to the hospital for any reason were in better clinical condition compared with men. This observation may be partially explained by the proportion of pregnant women in the study population. These findings suggest that future studies should examine pregnant women with HIV/AIDS as a separate population group to avoid bias in analysis. (Gend Med. 2010;7:28-38) (C) 2010 Excerpta Medica Inc.

Cannabis use before age 15 and subsequent executive functioning

Background Many studies have suggested that adolescence is a period of particular vulnerability to neurocognitive effects associated with substance misuse. However, few large studies have measured differences in cognitive performance between chronic cannabis users who started in early adolescence (before age 15) with those who started later. Aims To examine the executive functioning of individuals who started chronic cannabis use before age 15 compared with those who started chronic cannabis use after 15 and controls. Method We evaluated the performance of 104 chronic cannabis users (49 early-onset users and 55 late-onset users) and 44 controls who undertook neuropsychological tasks, with a focus on executive functioning. Comparisons involving neuropsychological measures were performed using generalised linear model analysis of variance (ANOVA). Results The early-onset group showed significantly poorer performance compared with the controls and the late-onset group on tasks assessing sustained attention, impulse control and executive functioning. Conclusions Early-onset chronic cannabis users exhibited poorer cognitive performance than controls and late-onset users in executive functioning. Chronic cannabis use, when started before age 15, may have more deleterious effects on neurocognitive functioning.

Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental wernicke's encephalopathy

Although earlier studies on thiamine deficiency have reported increases in extracellular glutamate concentration in the thalamus, a vulnerable region of the brain in this disorder, the mechanism by which this occurs has remained unresolved. Treatment with pyrithiamine, a central thiamine antagonist, resulted in a 71 and 55% decrease in protein levels of the astrocyte glutamate transporters GLT-1 and GLAST, respectively, by immunoblotting in the medial thalamus of day 14 symptomatic rats at loss of righting reflexes. These changes occurred prior to the onset of convulsions and pannecrosis. Loss of both GLT-1 and GLAST transporter sites was also confirmed in this region of the thalamus at the symptomatic stage using immunohistochemical methods. In contrast, no change in either transporter protein was detected in the non-vulnerable frontal parietal cortex. These effects are selective; protein levels of the astrocyte GABA transporter GAT-3 were unaffected in the medial thalamus. In addition, astrocyte-specific glial fibrillary acidic protein (GFAP) content was unchanged in this brain region, suggesting that astrocytes are spared in this disorder. Loss of GLT-1 or GLAST protein was not observed on day 12 of treatment, indicating that down-regulation of these transporters occurs within 48 h prior to loss of righting reflexes. Finally, GLT-1 content was positively correlated with levels of the neurofilament protein alpha -internexin, suggesting that early neuronal drop-out may contribute to the down-regulation of this glutamate transporter and subsequent pannecrosis. A selective, focal loss of GLT-1 and GLAST transporter proteins provides a rational explanation for the increase in interstitial glutamate levels, and may play a major role in the selective vulnerability of thalamic structures to thiamine deficiency-induced cell death.

An integrative approach for studying the etiology of alcoholism and other addictions

Studies of alcoholism etiology often focus on genetic or psy-chosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions — behavioral undercontrol, pharmacologic vulnerability, negative affect regulation — addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.

Glutamate(NMDA) receptor NR1 subunit mRNA expression in Alzheimer's disease

We analyzed the expression profile of two NMDAR1 mRNA isoform subsets. NR1(0xx) and NR1(1xx), in discrete regions of human cerebral cortex. The subsets are characterized by the absence or presence of a 21-amino acid N-terminal cassette. Reverse transcription polymerase chain reaction for NR1 isoforms was performed on total RNA preparations from spared and susceptible regions from 10 pathologically confirmed Alzheimer's disease (AD) cases and 10 matched controls. Primers spanning the splice insert yielded two bands, 342 bp (NR1(0xx)) and 405 bp (NR1(1xx)), on agarose gel electrophoresis. The bands were visualized with ethidium and quantified by densitometry. NR1(1xx) transcript expression was calculated as a proportion of the NR1(1xx) + NR1(0xx) total. Values were significantly lower in AD cases than in controls in mid-cingulate cortex, p < 0.01, superior temporal cortex, p < 0.01 and hippocampus, p similar to 0.05. Cortical proportionate NR1(1xx) transcript expression was invariant over the range of ages acid areas of controls tested, at similar to 50%. This was also true for AD motor and occipital cortex. Proportionate NR1(1xx) expression in AD cingulate and temporal cortex was lower at younger ages and increased with age: this regression was significantly different from that in the homotropic areas of controls. Variations in NR1 N-terminal cassette expression may underlie the local vulnerability to excitotoxic damage of some areas in the AD brain. Alternatively, changes in NR1 mRNA expression may arise as a consequence of the AD disease process.

Curriculum development for professional ethics in Australian human service university programmes

Australian academics and practitioners in the human services are particularly susceptible to social, political and economic influences in respect of their relevance, viability and operations. In fact, it can be argued that the impact of these influences has placed human service practitioners and academics in a perpetual state of vulnerability. Australian universities have been challenged to make their programmes more relevant and viable to the community at large, and practitioners face increasing workloads with limited resources based on restricted fiscal allocation, and the changing relationship between government and service providers. Drawing on interview data from twenty-one (n = 21) practitioners, this article highlights their identified problems regarding the notion of professionalism in the human services with a particular focus on ethical dilemmas in human service practice. Gleaning these details will be a basis for recommending necessary professionalethics curricula content in human services programmes offered in Australian universities. Moreover, while the research data is Australian based, the authors contend that the universal theories and principles underpinning human service practice justify the significance and value of the data as an important source for international consideration in curriculum development of human service academic programmes.

Begging and food distribution in crimson rosella (Platycercus elegans) broods: why don't hungry chicks beg more?

Altricial nestlings solicit food by begging and engaging in scramble competition. Solicitation displays can thus signal both hunger and competitive ability. I examined nestling solicitation and parental responses in crimson rosellas (Platycercus elegans), a species in which parents engage in complex patterns of food allocation and appear to control the distribution of food. By manipulating the hunger of individual chicks and entire broods, I assessed how chick behaviours and parental food allocation varied with hatching rank, level of hunger, and intensity of nestling competition. Last-hatched chicks begged more than first-hatched chicks irrespective of individual hunger levels. The two parents combined fed individually hungry chicks more, but mothers and fathers varied in their responses to begging chicks: fathers fed last-hatched chicks in proportion to their begging intensity, whereas mothers fed chicks equally. Since fathers generally allocate more food to first-hatched chicks, fathers appear to use begging rates to adjust food allocation to non-preferred chicks within the brood. When I manipulated brood hunger levels, begging rates increased for first- and last-hatched chicks suggesting that chick begging rates are sensitive to the level of competition. This study shows that begging by rosella chicks does not correlate with hunger in a straightforward way and that the primary patterns of food allocation by parents art: not influenced by chick begging. Thus the benefits of increased begging may be limited for nestlings in this species.

Personality and the genetic risk for alcohol dependence

The extent to which the genetic risk for alcohol dependence (AD) and conduct disorder (CD) and their common genetic risk overlap with genetic factors contributing to variation in dimensions of personality was examined in a study of 6,453 individuals from 3,383 adult male and female same-sex and unlike-sex twin pairs from the Australian Twin Registry. The associations between the personality dimensions of positive emotionality, negative emotionality, and AD and CD risk were modest. whereas the associations between behavioral undercontrol and AD and CD risk were substantially higher. Genetic influences contributing to variation in behavioral undercontrol accounted for about 40% of the genetic variation in AD and CD risk and about 90% of the common genetic risk for AD and CD. These results suggest that genetic factors contributing to variation in dimensions of personality, particularly behavioral undercontrol. account for a substantial proportion of the genetic diathesis for AD and most of the common genetic diathesis for AD and CD among both men and women.

Some new killing trick: Welfare reform and drug markets in a U.S. urban ghetto

Ethnographic data collected over a 5-year period is analyzed to determine how the Personal Responsibility & Work Opportunity Reconciliation Act of 1996 (PRWORA) has affected the lives of young male drug dealers from AIDS-afflicted families residing in Detroit. The data analysis indicated that the participants perceived drug dealing as the only viable employment opportunity for meeting the quotidian & health care needs of their families. The findings also revealed that the participants were highly aware of local political processes & the necessities of caring for relatives living with AIDS. Additional attention is dedicated to exploring the state of MI's rationale for ending the General Assistance Program, the sociocultural foundations of the PRWORA, various stipulations of the PRWORA, & how the PRWORA has augmented the legal vulnerability of welfare recipients. It is concluded that the PRWORA will force many welfare recipients to engage in illicit activities & will generally decrease recipients' health. 59 References. J. W. Parker

On the intrinsic capacity for increase of Australian flying-foxes (Pteropus spp., Megachiroptera)

In the reproductive biology of organisms, a continuum exists from "highly reproductive species" at one end to "survivor species" at the other end. Among other factors, the position of a species along this continuum affects its sensitivity to human exploitation and its vulnerability to extinction. Flying foxes are long-lived, seasonal breeders, with a rigid, well-defined breeding season that is largely or wholly genetically determined. Unlike opportunistic, highly reproductive species, such as rabbits or mice, female flying foxes are unable to produce viable young before their second or third year of life, and are then capable of producing just one young per year. Such a breeding strategy will be successful only if flying-foxes are long-lived and suffer naturally low mortality rates. In this paper, we assess the vulnerability of flying foxes to extinction, using basic parameters of reproduction observed in the wild, and in captive breeding colonies of P. poliocephalus, P. alecto and P. scapulatus, and survival rates that are likely to apply to Australian conditions. Our models show explicitly that flying-fox populations have a very low capacity for increase, even under the most ideal conditions. The implications of our models are discussed in reference to the long-term management and conservation needs of Australian flying foxes. We conclude that current death-rates of flying-foxes in NSW and Queensland fruit orchards are putting state populations at serious risk.

Relat??rio final do projeto desenvolvimento de capacidade de lideran??a (Brasil-Canad??)

Desde o in??cio de 2000, a Canada School of Public Service (CSPS) e a Escola Nacional de Administra????o P??blica (ENAP) demonstraram interesse na possibilidade de coopera????o para desenvolver capacidades de gest??o de servidores p??blicos brasileiros. Um acordo assinado em 2003, inicialmente foi planejado para ser uma parceria de tr??s anos entre as duas escolas. No entanto, a parceria continua at?? hoje e agora estamos no final do segundo, e ??ltimo projeto de coopera????o t??cnica financiado pela Canadian International Development Agency (CIDA) entre Brasil e Canad??, denominado ???Desenvolvimento da Capacidade de Governan??a???. Este relat??rio representa o resultado deste segundo projeto, o qual ampliou o esfor??o de capacita????o da primeira parceria, focando agora em funcion??rios p??blicos mais pr??ximos da "linha de frente" da presta????o de servi??os, aumentando assim a efic??cia do governo nessas ??reas. O projeto mostrou ser bem-sucedido, principalmente, porque seguiu de perto os princ??pios do desenvolvimento eficaz e sustent??vel. Considerando a sua miss??o de desenvolver compet??ncias de servidores p??blicos, a ENAP deu prioridade, dentro deste projeto de coopera????o com o Canad??, a atividades que visam refor??ar a capacidade de governan??a do pa??s, trabalhando em conjunto com escolas em cinco regi??es: Norte, Nordeste, Centro-Oeste, Sudeste e Sul, com especial ??nfase nas ??reas mais pobres do pa??s, localizadas nas regi??es Norte e Nordeste. Foram participantes-chave neste projeto: i) seis escolas brasileiras regionais de administra????o p??blica; ii) uma das principais institui????es acad??micas do Canad?? - Queen's University, e iii) o Minist??rio do Desenvolvimento Social e Combate ?? Fome e tr??s Secretarias de Ra??a, Direitos Humanos e Pol??ticas para as Mulheres. Neste projeto, a CSPS compartilhou suas metodologias em educa????o a dist??ncia, lideran??a e gest??o p??blica. Trabalhando com parceiros brasileiros, ela tamb??m transferiu e adaptou curr??culos e conte??dos de seus cursos. A CIDA forneceu $1.845.000,00 por meio da Programa de Interc??mbio de Conhecimentos para a Promo????o da Eq??idade (PIPE) Brasil-Canad??. A ENAP e as EPBs contribu??ram com $993,752 e a CSPS contribuiu com material de curso, conhecimento e apoio t??cnico no valor de $ 1.000.000