Genetic in long QT syndromes

The long QT syndrome (LQTS) is a genetic disorder characterized by prolongation of the QT interval in the electrocardiogram (ECG) and a propensity to "torsades de pointes" ventricular tachycardia frequently leading to syncope, cardiac arrest, or sudden death usually in young otherwise healthy individuals. LQTS caused by mutations of predominantly potassium and sodium ion channel genes or channel-interacting proteins leading to positive overcharge of myocardial cell with consequent heterogeneous prolongation of repolarization in various layers and regions of myocardium. These conditions facilitate the early after-depolarization and reentry phenomena underlying development of polymorphic ventricular tachycardia observed in patients with LQTS. Obtaining detailed patient history regarding cardiac events in the patient and his/her family members combined with careful interpretation of standard 12-lead ECG (with precise measurement of QT interval in all available ECGs and evaluation of T-wave morphology) usually is sufficient to diagnose the syndrome. The LQTS show great genetic heterogeneity and has been identified more than 500 mutations distributed in 10 genes: KCNQ1, HERG, SCN5A, KCNE1, KCNE2, ANKB, KCNJ2, CACNA1A, CAV3 and SCN4B. Despite advances in the field, 25-30% of patients remain undiagnosed genetic. Genetic testing plays an important role and is particularly useful in cases with nondiagnostic or borderline ECG findings.

Wirkmechanismen sozial-interpersoneller Faktoren in einer Stichprobe ehemals politisch Inhaftierter der DDR

Social/interpersonal factors play a central role in PTSD. Previous studies have indicated the specific pathways along which these factors take effect. The study reported here investigates these pathways with reference to a sample of former political prisoners jailed in the GDR. It examines dysfunctional disclosure of traumatic experiences, social acknowledgement, general social support and forgiveness tendencies. For the study N = 86 non-treatment-seeking former political prisoners were recruited (average age 64 years). The instruments employed were the Disclosure of Trauma questionnaire, the Social Acknowledgement questionnaire, the Social Support questionnaire, the Tendency to Forgive scale and the Impact of Event scale (revised). Dysfunctional disclosure was proximally, social acknowledgement distally and general social support and forgiveness indirectly associated with PTSD symptomatologies. The study casts light on potential pathways to posttraumatic adjustment, with special reference to social/interpersonal factors.

Studies on regulation of skeletal muscle differentiation by growth factors

Skeletal muscle differentiation involves sequential events in which proliferating undifferentiated myoblasts withdraw from the cell cycle and fuse to form multinucleated myotubes. The process of fusion is accompanied by the disappearance of proteins associated with cell proliferation and the coordinate induction of a battery of muscle-specific gene products, which includes the muscle isoenzyme of creatine kinase, nicotinic acetylcholine receptor, and contractile proteins such as alpha-actin. The molecular events associated with myogenesis are particularly amenable to experimental analysis because the events which occur in vivo can be recapitulated in vitro using established muscle cell lines. Initiation of myogenic differentiation in vitro can be achieved by removing serum from the culture medium. Myogenesis, therefore, can be considered to be regulated through a repression-type of mechanism by components in serum. The objectives of this project were to identify the components involved in regulation of myogenesis and approach the mechanism(s) whereby these components achieve their regulatory function. Initially, the effects of a series of polypeptide growth factors on myogenesis were examined. Among them TGF$\beta$ and FGF were found to be potent inhibitors of myogenic differentiation which did not affect cell proliferation. The inhibitory effects of these growth factors on differentiation requires their persistent presence in the culture medium. After myoblasts have undergone fusion, they become refractory to the inhibitory effects of TGF$\beta$, FGF, and serum. When fusion is inhibited by the presence of EGTA, a Ca$\sp{2+}$ chelator, muscle-specific genes are expressed reversibly upon removal of inhibitory growth factors. Subsequent exposure of biochemically differentiated cells to serum or TGF$\beta$ leads to down-regulation of muscle-specific genes. Stimulation with serum also leads to reentry of myocytes into the cell cycle, whereas fused myotubes are irreversibly and terminally differentiated. Measurement of levels of TGF$\beta$ receptors reveals that under non-fusing conditions, TGF$\beta$ receptor levels in biochemically differentiated myocytes remained as high as in undifferentiated myoblasts, while during terminal differentiation, TGF$\beta$ receptors decreased at least five-fold. Thus, down-regulation of TGF$\beta$ receptors is coupled to irreversible differentiation, but not reversible differentiation in the absence of fusion. The possible involvement of second messenger systems, such as cAMP and protein kinase C, in the pathway(s) by which TGF$\beta$, FGF, or serum factors transduce their signals from the cell surface to the nucleus was also examined. The results showed that myogenic differentiation is subject to negative regulation through cAMP elevation-dependent and cAMP elevation-independent pathways and that serum mitogens, TGF$\beta$ and FGF inhibit differentiation through a mechanism independent of cAMP-elevation or protein kinase C activation. ^

Patterns of care and outcomes for pregnant inmates and their infants in Texas state prisons: Epidemiologic and ethnographic analyses

Female inmates make up the fastest growing segment in our criminal justice system today. The rapidly increasing trend for female prisoners calls for enhanced efforts to strategically plan the correctional facilities that address the needs of this growing population, and to work with communities to prevent crime in women. The incarcerated women in the U.S. have an estimated 145,000 minor children who are predisposed to unique psychosocial problems as a result of parental incarceration.^ This study examined the patterns of care and outcomes for pregnant inmates and their infants in Texas state prisons between 1994 and 1996. The study population consists of 202 pregnant inmates who delivered in a 2-year period, and a randomly sampled comparison cohort of 804 women from general Texas population, matched on race and educational levels. Both quantitative and qualitative data were used to elucidate the inmates' risk-factor profile, delivery/birth outcomes, and the patterns of care during pregnancy. The continuity-of-care issues for this population were also explored.^ Epidemiologic data were derived from multiple record systems to establish the comparison between two cohorts. A significantly great proportion of the inmates have prior lifestyle risk-factors (smoking, alcohol, and illicit drug abuse), poorer health status, and worse medical history. However, most of these existing risk-factors seem to show little manifestation in their current pregnancy. On the basis of maternal labor/delivery outcome and a number of neonatal indicators, this study found some evidence of a better pregnancy outcome for the inmate cohort when compared to the comparison group. Some possible explanations of this paradox were discussed. Seventeen percent of inmates gave birth to infants with suspected congenital syphilis. The placement patterns for the infants' care immediately after birth were elucidated.^ In addition to the quantitative data, an ethnographic approach was used to collect qualitative data from a subset of the inmate cohort (n = 20) and 12 care providers. The qualitative data were analyzed for their contents and themes, giving rise to a detailed description of the inmates' pregnancy experience. Eleven themes emerged from the study's thematic analysis, which provides the context for interpreting the epidemiologic data.^ Meaningful findings in this study were presented in a three-dimensional matrix to shed light on the apparent relationship between outcome indicators and their potential determinants. The suspected "linkages" between the outcome and their determinants can be used to generate hypotheses for future studies. ^

Horizontal ridge augmentation in conjunction with or prior to implant placement in the anterior maxilla: a systematic review.

PURPOSE To systematically review clinical studies examining the survival and success rates of implants in horizontal ridge augmentation, either prior to or in conjunction with implant placement in the anterior maxilla. MATERIALS AND METHODS A literature search was undertaken up to September 2012 including clinical studies in English with ≥ 10 consecutively treated patients and a mean follow-up of at least 12 months. Two reviewers screened the pertinent articles and extracted the data. Key words focused on the outcome parameters (implant success, implant survival, horizontal bone gain, and intra- and postoperative complications) in studies utilizing either a simultaneous approach (ridge augmentation performed at the time of implant placement) or a staged approach (ridge augmentation performed prior to implant placement) were analyzed. RESULTS A total of 13 studies met the inclusion criteria, with 2 studies in the simultaneous group and 11 studies in the staged group. In the simultaneous group, survival rates of implants were 100% in both studies, with one study also reporting a 100% implant success rate. No data on horizontal bone gain were available. In the staged group, success rates of implants placed in horizontally augmented ridges ranged from 96.8% to 100% (two studies), and survival rates ranged from 93.5% to 100% (five studies). However, follow-up periods differed widely (up to 4.1 years). Mean horizontal bone gain determined at reentry (implant placement) ranged from 3.4 to 5.0 mm with large overall variations (0 to 9.8 mm, five studies). Intraoperative complications were not reported. Postsurgical complications included mainly mucosal dehiscences (five studies), and, occasionally, complete failures of block grafts were described in one study. CONCLUSIONS Staged and simultaneous augmentation procedures in the anterior maxilla are both associated with high implant success and survival rates. The level of evidence, however, is better for the staged approach than for the simultaneous one.

Paroxysmale supraventrikuläre Tachykardien – Mechanismen, Diagnostik und Therapie

Supraventrikuläre Tachykardien sind definitionsgemäß Tachykardien, die ihren Ursprungsort oberhalb der His-Bündel-Bifurkation haben. Der Ausdruck supraventrikulär ist aber ungenau und historisch bedingt. Die häufigsten supraventrikulären Tachykardien im eigentlichen Sinn umfassen die AV-Knoten-Reentry-Tachykardie und die AV-Reentry-Tachykardie, wobei die letztere die Ventrikel als integraler Bestandteil der kreisenden Erregung braucht und somit also nicht rein supraventrikulär ist. Die häufigste supraventrikuläre Tachykardie überhaupt ist aber die Sinustachykardie, die in der Regel physiologisch ist, gefolgt von Vorhofflimmern und Vorhofflattern. Da Vorhofflimmern und Vorhofflattern in dieser Ausgabe der Therapeutischen Umschau gesondert besprochen werden, liegt der Fokus dieser Übersichtsarbeit in der Diskussion von Mechanismen, Diagnostik und Therapie der AV-Knoten-Reentry-Tachykardie, der AV-Reentry-Tachykardie via akzessorische Leitungsbahn und am Rande auch der fokalen atrialen Tachykardie.

Management of patients during hunger strike and refeeding phase

OBJECTIVE Hunger strikers resuming nutritional intake may develop a life-threatening refeeding syndrome (RFS). Consequently, hunger strikers represent a core challenge for the medical staff. The objective of the study was to test the effectiveness and safety of evidence-based recommendations for prevention and management of RFS during the refeeding phase. METHODS This was a retrospective, observational data analysis of 37 consecutive, unselected cases of prisoners on a hunger strike during a 5-y period. The sample consisted of 37 cases representing 33 individual patients. RESULTS In seven cases (18.9%), the hunger strike was continued during the hospital stay, in 16 episodes (43.2%) cessation of the hunger strike occurred immediately after admission to the security ward, and in 14 episodes (37.9%) during hospital stay. In the refeed cases (n = 30), nutritional replenishment occurred orally, and in 25 (83.3%) micronutrients substitutions were made based on the recommendations. The gradual refeeding with fluid restriction occurred over 10 d. Uncomplicated dyselectrolytemia was documented in 12 cases (40%) within the refeeding phase. One case (3.3%) presented bilateral ankle edemas as a clinical manifestation of moderate RFS. Intensive medical treatment was not necessary and none of the patients died. Seven episodes of continued hunger strike were observed during the entire hospital stay without medical complications. CONCLUSIONS Our data suggested that seriousness and rate of medical complications during the refeeding phase can be kept at a minimum in a hunger strike population. This study supported use of recommendations to optimize risk management and to improve treatment quality and patient safety in this vulnerable population.

Slow conduction in mixed cultured strands of primary ventricular cells and stem cell-derived cardiomyocytes

Modern concepts for the treatment of myocardial diseases focus on novel cell therapeutic strategies involving stem cell-derived cardiomyocytes (SCMs). However, functional integration of SCMs requires similar electrophysiological properties as primary cardiomyocytes (PCMs) and the ability to establish intercellular connections with host myocytes in order to contribute to the electrical and mechanical activity of the heart. The aim of this project was to investigate the properties of cardiac conduction in a co-culture approach using SCMs and PCMs in cultured cell strands. Murine embryonic SCMs were pooled with fetal ventricular cells and seeded in predefined proportions on microelectrode arrays to form patterned strands of mixed cells. Conduction velocity (CV) was measured during steady state pacing. SCM excitability was estimated from action potentials measured in single cells using the patch clamp technique. Experiments were complemented with computer simulations of conduction using a detailed model of cellular architecture in mixed cell strands. CV was significantly lower in strands composed purely of SCMs (5.5 ± 1.5 cm/s, n = 11) as compared to PCMs (34.9 ± 2.9 cm/s, n = 21) at similar refractoriness (100% SCMs: 122 ± 25 ms, n = 9; 100% PCMs: 139 ± 67 ms, n = 14). In mixed strands combining both cell types, CV was higher than in pure SCMs strands, but always lower than in 100% PCM strands. Computer simulations demonstrated that both intercellular coupling and electrical excitability limit CV. These data provide evidence that in cultures of murine ventricular cardiomyocytes, SCMs cannot restore CV to control levels resulting in slow conduction, which may lead to reentry circuits and arrhythmias.

Hepatitis B and C infections in U.S. incarcerated populations: Prevalence and related mortality

Published reports have consistently indicated high prevalence of serologic markers for hepatitis B (HBV) and hepatitis C (HCV) infection in U.S. incarcerated populations. Quantifying the current and projected burden of HBV and HCV infection and hepatitis-related sequelae in correctional healthcare systems with even modest precision remains elusive, however, because the prevalence and sequelae of HBV and HCV in U.S. incarcerated populations are not well-studied. This dissertation contributes to the assessment of the burden of HBV and HCV infections in U.S. incarcerated populations by addressing some of the deficiencies and gaps in previous research. ^ Objectives of the three dissertation studies were: (1) To investigate selected study-level factors as potential sources of heterogeneity in published HBV seroprevalence estimates in U.S. adult incarcerated populations (1975-2005), using meta-regression techniques; (2) To quantify the potential influence of suboptimal sensitivity of screening tests for antibodies to hepatitis C virus (anti-HCV) on previously reported anti-HCV prevalence estimates in U.S. incarcerated populations (1990-2005), by comparing these estimates to error-adjusted anti-HCV prevalence estimates in these populations; (3) To estimate death rates due to HBV, HCV, chronic liver disease (CLD/cirrhosis), and liver cancer from 1984 through 2003 in male prisoners in custody of the Texas Department of Criminal Justice (TDCJ) and to quantify the proportion of CLD/cirrhosis and liver cancer prisoner deaths attributable to HBV and/or HCV. ^ Results were as follows. Although meta-regression analyses were limited by the small body of literature, mean population age and serum collection year appeared to be sources of heterogeneity, respectively, in prevalence estimates of antibodies to HBV antigen (HBsAg+) and any positive HBV marker. Other population characteristics and study methods could not be ruled out as sources of heterogeneity. Anti-HCV prevalence is likely somewhat higher in male and female U.S. incarcerated populations than previously estimated in studies using anti-HCV screening tests alone without the benefit of repeat or additional testing. Death rates due to HBV, HCV, CLD/cirrhosis, and liver cancer from 1984 through 2003 in TDCJ male prisoners exceeded state and national rates. HCV rates appeared to be increasing and disproportionately affecting Hispanics. HCV was implicated in nearly one-third of liver cancer deaths. ^

Transcriptional and translational regulators of gene expression in germ cell development

Germ cell development is a highly coordinated process driven, in part, by regulatory mechanisms that control gene expression. Not only transcription, but also translation, is under regulatory control to direct proper germ cell development. In this dissertation, I have focused on two regulators of germ cell development. One is the homeobox protein RHOX10, which has the potential to be both a transcriptional and translational regulator in mouse male germ cell development. The other is the RNA-binding protein, Hermes, which functions as a translational regulator in Xenopus laevis female germ cell development. ^ Rhox10 is a member of reproductive homeobox gene X-(linked (Rhox) gene cluster, of which expression is developmentally regulated in developing mouse testes. To identify the cell types and developmental stages in which Rhox10 might function, I characterized its temporal and spatial expression pattern in mouse embryonic, neonatal, and adult tissues. Among other things, this analysis revealed that both the level and the subcellular localization of RHOX10 are regulated during germ cell development. To understand the role of Rhox10 in germ cell development, I generated transgenic mice expressing an artificial microRNA (miRNA) targeting Rhox10. While this artificial miRNA robustly downregulated RHOX10 protein expression in vitro, it did not significantly reduce RHOX10 expression in vivo. So I next elected to knockdown RHOX10 levels in spermatogonial stem cells (SSCs), which I found highly express both Rhox10 mRNA and RHOX10 protein. Using a recently developed in vitro culture system for SSCs combined with a short-hairpin RNA (shRNA) approach, I strongly depleted RHOX10 expression in SSCs. These RHOX10-depleted cells exhibited a defect in the ability to form stem cell clusters in vitro. Expression profiling analysis revealed many genes regulated by Rhox10, including many meiotic genes, which could be downstream of Rhox10 in a molecular pathway that controls SSC differentiation. ^ RNA recognition motif (RRM) containing protein, Hermes is localized in germ plasm, where dormant mRNAs are also located, of Xenopus oocytes, which implicates its role in translational regulator. To understand the function of Hermes in oocyte meiosis, I used a morpholino oligonucleotide (MO) based knockdown approach. Microinjection of Hermes MO into fully grown oocytes, which are arrested in meiotic prophase, caused acceleration of oocytes reentry into meiosis (i.e., maturation) upon progesterone induction. Using a candidate approach, I identified at least three targets of Hermes: Ringo/Spy, Xcat2, and Mos. Ringo/Spy and Mos are known to have functions in oocyte maturation, while Ringo/Spy, Xcat2 mRNA are localized in the germ plasm of oocytes, which drives germ cell specification after fertilization. This led me to propose that Hermes functions in both oocyte maturation and germ cell development through its ability to regulate 3 crucial target mRNAs. ^

Estrategias para la reinserción social de jóvenes en conflicto con la ley

La justicia penal adolescente es un sistema de administración judicial que extiende los derechos y garantías del debido proceso a los adolescentes a quienes se acuse de haber participado en la comisión de una infracción a la ley penal. Se podría decir que las finalidades de la justicia penal juvenil, por orden de importancia son: Administrar justicia de forma democrática. Fomentando la responsabilización del adolescente que ha cometido una infracción penal; promoviendo su integración social y favoreciendo la participación de la comunidad en el proceso de reinserción social, mediante la oferta de servicios y programas para el cumplimiento de medidas socio-educativas. Cabe preguntarse ¿Las instituciones correccionales son coadyuvantes en la reinserción de los jóvenes en conflicto con la ley de tal modo que no vuelvan a confrontar con el orden jurídico vigente cuando egresen? La respuesta es muy compleja porque si bien desde la situación de las instituciones el aislamiento que sufre el joven no les da defensas para poder cambiar sus circunstancias de vida a la hora de reingresar a la sociedad y esto lleva a una alta probabilidad de volver a delinquir. Sin embargo las Ciencias Sociales plantean otras alternativa para logran la inserción de los jóvenes, una de ellas, se inclina a la estimulación de la resiliencia. Esta implica: sobreponerse a las dificultades y tener éxito a pesar de estar expuestos a situaciones de alto riesgo; mantener la competencia bajo presión, esto significa adaptarse con éxito y recuperarse de un trauma ajustándose de forma exitosa a los acontecimientos negativos de la vida.

Petrology and geochemistry of oceanic intraplate sheet-flow basalts at DSDP Hole 89-462A

Reentry of Hole 462A during Leg 89 resulted in the penetration of a further 140 m of basalt sheet-flows similar to those found during Leg 61 at the same site. Twelve volcanic units (45 to 56) were recognized, comprising a series of rapidly extruded, interlayered aphyric and poorly clinopyroxene-plagioclase-olivine phyric, nonvesicular basalts. All exhibit variable, mild hydration and oxidation, relative to fresh oceanic basalts, produced under reducing, low-CO2-activity conditions within the zeolite facies. Secondary assemblages are dominated by smectites, zeolites, and pyrite, produced by low-temperature reaction with poorly oxygenated seawater. No systematic mineralogical or chemical changes are observed with depth, although thin quenched units and more massive hypocrystalline units exhibit slightly different alteration parageneses. Chemically, the basalts are olivine- and quartz-normative tholeiites, characterized by low incompatible-element abundances, similar to mildly enriched MORB (approaching T-type), with moderate, chrondite-normalized, large-ionlithophile- element depletion patterns and generally lower or near-chrondritic ratios for many low-distribution-coefficient (KD) element pairs. In general, relative to cyclic MORB chemical variation, they are uniform throughout, although 3 chemical megagroups and 22 subgroups are recognized. It is considered that the megagroups represent separate low-pressure-fractionated systems (olivine + Plagioclase ± clinopyroxene), whereas minor variations within them (subgroups) indicate magma mixing and generation of near-steady-state conditions. Overall, relatively minor fractionation coupled with magma mixing produced a series of compositionally uniform lavas. Parental melts were produced by similar degrees of partial melting, although the source may have varied slightly in LIL-element content.

Compañeros de ruta, reencuentro de ex presos políticos cordobeses

El propósito de este trabajo es investigar los motivos, anhelos, sueños, deseos que llevan a un grupo de entre 20 y 25 ex presos políticos a reunirse semanalmente en el local del sindicato Luz y Fuerza, Córdoba. Optamos por entrevistar a quienes daban la sensación de ser más participativos o más explícitos, en la elección procuramos que hubiesen casi por igual miembros de las dos organizaciones mayoritarias en el pasado: Montoneros y Partido Revolucionario de los Trabajadores. El celo a la hora de elegir se entronca con las subculturas que emergieron de las organizaciones. Otro aspecto observado es la cuestión de género, mujeres y hombres, equitativamente incorporados, se constituyeron en narradores.2 En la ciudad mediterránea hubo alrededor de dos mil detenidos por causas políticas a partir de la dictadura que iniciara Jorge Rafael Videla. La curiosidad social es acicateada por el número exiguo de ex-represaliados que constituyen la comisión de presos políticos, que entre otras tareas peticiona ante las autoridades solicitando reivindicaciones a raíz de su condición de ex detenidos, organizan eventos sociales y políticos, gestionan los ex centros de detención convertidos en "museos de la memoria", impulsan los juicios contra los ex represores, editan publicaciones. Concurrimos a las reuniones semanales, a asados, "locreadas"; empleamos en las investigaciones la observación participante. La participación se dio en eventos, en compartir ruedas de mate en la casa de los entrevistados, íntimas ruedas de café, por un fenómeno de indexicalidad en relación con el discurso ideológico pudimos avanzar en la profundidad de la conversación. Además, de las entrevistas en profundidad, analizamos material periodístico y material escrito por los detenidos; cuando la emoción del entrevistado dificultaba la conversación, en algunos casos nos remitieron a elaboraciones suyas sobre la situación planteada.. Nos favoreció, en el trabajo, el hecho de haber participado en la vida política, y el tener familiares que lucharon junto a los ex-represaliados. A pesar de ello no fue fácil llegar a subjetividades que hacía largo tiempo se hallaban abroqueladas. Mead e Erving Goffman nos acompañaron en el camino de reconocimiento de los selfs en la dramaturgia montada en el local de Luz y Fuerza

Las cárceles en el Rosario de la 2da mitad de siglo XIX : Fuentes y enfoques

Este artículo revisa modos de abordaje de las cárceles a partir de los archivos rosarinos. Mediante un recorrido por los diversos fondos documentales se formulan interrogantes que van desde las responsabilidades judiciales, policiales y ejecutivas frente al movimiento diario de la cárcel hasta la materialidad misma de sus condiciones edilicias y de su aprovisionamiento, con el objetivo de presentar cierta dinámica de funcionamiento. La exploración de fuentes judiciales permite reconstruir dichas condiciones desde las voces de quienes habitaban estos sitios. Se revisa, además, la problemática relación entre las autoridades que comprendían las jurisdicciones de los detenidos reunidos físicamente en un mismo lugar, que además era el cuartel de gendarmes

El PRT-ERP y la lucha por la libertad de los presos políticos, 1971-1973

Este trabajo aborda la represión política de la militancia revolucionaria por parte del régimen militar y la problemática de los presos políticos en la etapa 1971-1973 en Argentina. Se realiza un análisis de las principales características de la legislación represiva. Centralmente refiere a las diferentes iniciativas desarrolladas por el PRT-ERP en relación con sus militantes presos y en particular a la constitución de una Comisión de familiares de presos políticos, estudiantiles y gremiales para la organización de la solidaridad y defensa de los mismos. Apuntamos a destacar la amplia actividad de defensa y solidaridad con los presos políticos desarrollada por un conjunto de organizaciones como un antecedente importante, pero no reconocido, para la constitución del movimiento de derechos humanos de la Argentina en 1975-1976