COVID-19 and novel mRNA vaccines in pregnancy: an updated literature review.

The novel coronavirus, SARS-CoV-2, or COVID-19, has affected the world on a pandemic scale resulting in catastrophic outcomes and deaths. Currently, there is limited safety data specific to mRNA vaccine use in pregnant or lactating individuals and the potential risks to a pregnant individual and the fetus are unknown. We report an updated literature review of current information and evidence available to aid in the decision whether to vaccinate against COVID-19 currently being made by pregnant individuals and their healthcare providers so that they are able to make a well-informed recommendation and decision.

Sequence-specific transcriptional activation by Myc and repression by Max.

The c-Myc oncoprotein, which is required for cellular proliferation, resembles in its structure a growing number of transcription factors. However, the mechanism of its action in vivo is not yet clear. The discovery of the specific cognate DNA-binding site for Myc and its specific heterodimerization partner, Max, enabled the use of direct experiments to elucidate how Myc functions in vivo and how this function is modulated by Max. Here we demonstrate that exogenously expressed Myc is capable of activating transcription in vivo through its specific DNA-binding site. Moreover, transcriptional activation by Myc is dependent on the basic region, the integrity of the helix-loop-helix and leucine zipper dimerization motifs located in the carboxy-terminal portion of the protein, and the regions in the amino terminus conserved among Myc family proteins. In contrast to Myc, exogenously expressed Max elicited transcriptional repression and blocked transcriptional activation by Myc through the same DNA-binding site. Our results suggest a functional antagonism between Myc and Max which is mediated by their relative levels in the cells. A model for the activity of Myc and Max in vivo is presented.

Transcription enhancer factor 1 interacts with a basic helix-loop-helix zipper protein, Max, for positive regulation of cardiac alpha-myosin heavy-chain gene expression.

The M-CAT binding factor transcription enhancer factor 1 (TEF-1) has been implicated in the regulation of several cardiac and skeletal muscle genes. Previously, we identified an E-box-M-CAT hybrid (EM) motif that is responsible for the basal and cyclic AMP-inducible expression of the rat cardiac alpha-myosin heavy chain (alpha-MHC) gene in cardiac myocytes. In this study, we report that two factors, TEF-1 and a basic helix-loop-helix leucine zipper protein, Max, bind to the alpha-MHC EM motif. We also found that Max was a part of the cardiac troponin T M-CAT-TEF-1 complex even when the DNA template did not contain an apparent E-box binding site. In the protein-protein interaction assay, a stable association of Max with TEF-1 was observed when glutathione S-transferase (GST)-TEF-1 or GST-Max was used to pull down in vitro-translated Max or TEF-1, respectively. In addition, Max was coimmunoprecipitated with TEF-1, thus documenting an in vivo TEF-1-Max interaction. In the transient transcription assay, overexpression of either Max or TEF-1 resulted a mild activation of the alpha-MHC-chloramphenicol acetyltransferase (CAT) reporter gene at lower concentrations and repression of this gene at higher concentrations. However, when Max and TEF-1 expression plasmids were transfected together, the repression mediated by a single expression plasmid was alleviated and a three- to fourfold transactivation of the alpha-MHC-CAT reporter gene was observed. This effect was abolished once the EM motif in the promoter-reporter construct was mutated, thus suggesting that the synergistic transactivation function of the TEF-1-Max heterotypic complex is mediated through binding of the complex to the EM motif. These results demonstrate a novel association between Max and TEF-1 and indicate a positive cooperation between these two factors in alpha-MHC gene regulation.

Pulsatile ocular blood flow during pregnancy.

PURPOSE: To study pulsatile ocular blood flow (POBF) throughout pregnancy. METHODS: We enrolled twenty-seven healthy women in the first trimester of gestation, only ten of which were followed through the second trimester, and fourteen non pregnant healthy women. In each subject we measured POBF with the POBF pneumotonometer (OBF Ltd. UK), IOP, blood pressure (BP) and heart rate (HR). An unpaired Student t-test was used to compare pregnant women with non-pregnant women, and a two-tailed paired Student t-test was used to compare the same women in the first and second trimester of pregnancy. p <0.05 is considered statistically significant. RESULTS: Results are presented as means +/- SD. In the first trimester of pregnancy the age was 32 +/- 6, POBF 1516.4 +/- 382 ml/min, IOP 13 +/- 3 mmHg, BP 92 +/- 6 mmHg, and HR 86 +/- 14 beats/min. In the second trimester POBF was 1629.11 +/- 352.4 ml/min, intraocular pressure (IOP) 12 +/- 3 mmHg, BP 96 +/- 3 mmHg, and HR 93 +/- 10 beats/min. In the control group the age was 27 +/- 9, POBF 972.23 +/- 329.3 ml/min, BP 88 +/- 4.3 mmHg, and HR 80 +/- 14 beats/min. POBF increases during the first trimester (p = 0.00008). In the second trimester POBF was higher compared to the first trimester (p = 0.0008). Non significant differences were observed for the other parameters. CONCLUSIONS: The POBF increases throughout gestation. During pregnancy there is an increase in estrogen which induces endothelial-dependent vasodilatation in several tissues. The estrogen changes may influence POBF.

[Impact of quality improvement process upon the state of nutritional support in a critical care unit]. / Impacto de un proceso de mejora de la calidad en el estado del soporte nutricional en una unidad de cuidados intensivos.

INTRODUCTION: In a preceding article the state of Nutritional support (NS) in an Intensive Care Unit (ICU) was documented [Martinuzzi A et al. Estado del soporte nutricional en una unidad de Cuidados críticos. RNC 2011; 20: 5-17]. In this follow-up work we set to assess the impact of several organizational, recording and educational interventions upon the current state of NS processes. MATERIALS AND METHODS: Interventions comprised presentation of the results of the audit conducted at the ICU before the institution's medical as well as paramedical personnel; their publication in a periodical, peer-reviewed journal; drafting and implementation of a protocol regulating NS schemes to be carried out at the ICU; and conduction of continuous education activities on Nutrition (such as "experts talks", interactive courses, and training in the implementation of the NS protocol). The state of NS processes documented after the interventions was compared with the results annotated in the preceding article. Study observation window ran between March the 1st, 2011 and May 31th, 2011, both included. RESULTS: Study series differed only regarding overall-mortality: Phase 1: 40.0% vs. Phase 2: 20.5%; Difference: 19.5%; Z = 1.927; two-tailed-p = 0.054. Interventions resulted in a higher fulfillment rate of the prescribed NS indication; an increase in the number of patients receiving ≥ 80% of prescribed energy; and a reduction in the number of NS lost days. Mortality was (numerically) lower in patients in which the prescribed NS scheme was fulfilled, NS was early initiated, and whom received ≥ 80% of prescribed energy. Adopted interventions had no effect upon average energy intakes: Phase 1: 574.7 ± 395.3 kcal/24 h⁻¹ vs. Phase 2: 591.1 ± 315.3 kcal/24 h⁻¹; two-tailed-p > 0.05. CONCLUSIONS: Educational, recording and organizational interventions might result in a better conduction of NS processes, and thus, in a lower mortality. Hemodynamic instability is still the most formidable obstacle for initiating and completing NS.

Development of a multi-layered psychosocial care system for children in areas of political violence.

Few psychosocial and mental health care systems have been reported for children affected by political violence in low- and middle income settings and there is a paucity of research-supported recommendations. This paper describes a field tested multi-layered psychosocial care system for children (focus age between 8-14 years), aiming to translate common principles and guidelines into a comprehensive support package. This community-based approach includes different overlapping levels of interventions to address varying needs for support. These levels provide assessment and management of problems that range from the social-pedagogic domain to the psychosocial, the psychological and the psychiatric domains. Specific intervention methodologies and their rationale are described within the context of a four-country program (Burundi, Sri Lanka, Indonesia and Sudan). The paper aims to contribute to bridge the divide in the literature between guidelines, consensus & research and clinical practice in the field of psychosocial and mental health care in low- and middle-income countries.

Impacto de un proceso de mejora de la calidad en el estado del soporte nutricional en una unidad de cuidados intensivos / Impact of quality improvement process upon the state of nutritional support in a critical care unit

Introducción: En un artículo precedente se documentó el estado del Soporte nutricional (SN) en una Unidad de Terapia Intensiva (UTI) [Martinuzzi A y cols. Estado del soporte nutricional en una unidad de Cuidados críticos. RNC 2011; 20: 5-17]. En este trabajo de seguimiento nos propusimos evaluar el impacto de varias intervenciones educativas, registrales y organizativas hechas en la Unidad sobre el estado actual de los procesos del SN. Material y método: Las intervenciones incluyeron la presentación de los resultados de la auditoría hecha en la UTI ante el plantel médico y paramédico de la institución; la publicación de los mismos en una revista periódica, arbitrada por pares; la redacción e implementación de un protocolo normativo de los esquemas de SN a conducir en la UTI; y la celebración de actividades de educación continuada en Nutrición (como "charlas con expertos", cursos interactivos, y capacitación en la implementación del protocolo de SN). El estado de los procesos de SN documentado tras las intervenciones se comparó con los resultados anotados en el trabajo precedente. La ventana de observación del estudio se extendió entre el 1 de Marzo del 2011 y el 31 mayo del 2011, ambos incluidos. Resultados: Las series de estudio difirieron entre sí solo respecto de la mortalidad: Fase 1: 40.0% vs. Fase 2: 20,5%; Diferencia: 19,5%; Z = 1,927; p-de-2-colas = 0,054. Las intervenciones hechas resultaron en una mayor tasa de cumplimiento de la indicación prescrita de SN; un aumento en el número de enfermos que recibieron > 80% de la energía prescrita; y una reducción en el número de días de SN perdidos. La mortalidad fue (numéricamente) menor en los pacientes en los que se cumplió el esquema prescrito de SN, el SN se inició tempranamente, y que recibieron > 80% de la energía prescrita. Las intervenciones adoptadas no tuvieron efecto sobre los aportes promedio de energía: Fase 1: 574,7 ± 395,3 kcal/24 h-1 vs. Fase 2: 591,1 ± 315,3 kcal/24 h-1; p > 0,05. Conclusiones: Las intervenciones educativas, registrales y organizativas pueden resultar en una mejor conducción de los procesos de SN, y con ello, en una menor mortalidad. La inestabilidad hemodinámica sigue siendo el obstáculo más formidable en el inicio y mantenimiento del SN (AU)

Introduction: In a preceding article the state of Nutritional support (NS) in an Intensive Care Unit (ICU) was documented [Martinuzzi A et al. Estado del soporte nutricional en una unidad de Cuidados críticos. RNC 2011; 20: 5-17]. In this follow-up work we set to assess the impact of several organizational, recording and educational interventions upon the current state of NS processes. Materials and methods: Interventions comprised presentation of the results of the audit conducted at the ICU before the institution's medical as well as paramedical personnel; their publication in a periodical, peerreviewed journal; drafting and implementation of a protocol regulating NS schemes to be carried out at the ICU; and conduction of continuous education activities on Nutrition (such as "experts talks", interactive courses, and training in the implementation of the NS protocol). The state of NS processes documented after the interventions was compared with the results annotated in the preceding article. Study observation window ran between March the 1st, 2011 and May 31th, 2011, both included. Results: Study series differed only regarding overallmortality: Phase 1: 40.0% vs. Phase 2: 20.5%; Difference: 19.5%; Z = 1.927; two-tailed-p = 0.054. Interventions resulted in a higher fulfillment rate of the prescribed NS indication; an increase in the number of patients receiving > 80% of prescribed energy; and a reduction in the number of NS lost days. Mortality was (numerically) lower in patients in which the prescribed NS scheme was fulfilled, NS was early initiated, and whom received > 80% of prescribed energy. Adopted interventions had no effect upon average energy intakes: Phase 1: 574.7 ± 395.3 kcal/24 h-1 vs. Phase 2: 591.1 ± 315.3 kcal/24 h1; two-tailed-p > 0.05. Conclusions: Educational, recording and organizational interventions might result in a better conduction of NS processes, and thus, in a lower mortality. Hemodynamic instability is still the most formidable obstacle for initiating and completing NS (AU)

An unusual reoccurrence of Waldenstrom's macroglobulinemia as pleural effusions that had a discordant response with treatment.

A 77-year-old female with a past medical history of Waldenstrom's macroglobulinemia presented with progressive shortness of breath and a newly diagnosed left pleural effusion. Numerous diagnostic studies were performed on the patient and finally a pleural biopsy confirmed pulmonary involvement of Waldenstrom's macroglobulinemia. As past studies have shown, Waldenstrom's involvement as a pulmonary process is uncommon. Unexpectedly, treatment with rituximab and fludarabine did decrease the patient's serum immunoglobulin M levels, but her pleural effusions never improved.

Enzymatic activity of poliovirus RNA polymerase synthesized in Escherichia coli from viral cDNA.

Plasmids have been constructed that contain DNA sequences that direct the expression of the poliovirus RNA-dependent RNA polymerase, in the form of recombinant fusion proteins. Inclusion of an additional gene for the poliovirus protease results in cleavage of the fusion protein to yield a 52-kDa, enzymatically active, polymerase protein, apparently identical to the functional enzyme isolated from virus-infected HeLa cells. A large amount of polymerase protein accumulates as particulate or insoluble material in bacteria, and this protein has little or no activity. However, significant amounts of soluble, active enzyme are recovered, such that the resulting specific activity of crude bacterial extracts is greater than that obtained from virus-infected HeLa cells. Purification of the enzyme from Escherichia coli is readily accomplished, and yields a preparation that will copy poliovirion RNA as template, in the presence of oligo(U) primer. The availability of cloned DNA sequences encoding catalytically active RNA polymerase will allow genetic manipulations to initiate structure-function studies of this enzyme.

Macroporous polyester-covered stent in an experimental abdominal aortic aneurysm model.

PURPOSE: To validate a recently described animal model of abdominal aortic aneurysm (AAA) and to assess a new macroporous polyester-covered stent for endovascular AAA exclusion. METHODS: Twenty adult sheep had AAAs surgically created by replacing a segment of the infrarenal aorta with an autologous jugular venous graft. Three months later, surviving animals underwent percutaneous implantation of macroporous polyester-covered nitinol stents; 3 animals with untreated AAAs served as controls. Follow-up surveillance included spiral computed tomography at 1 month and digital subtraction angiography at 3 and 6 months. Endografted animals were sacrificed at 1, 3, and 6 months after implantation; specimens from all animals were examined grossly and microscopically. RESULTS: Seven (35%) animals died within 24 hours of causes related to the technique; 1 animal developed paraplegia and was sacrificed on day 1. Three (25%) animals died of spontaneous aneurysm rupture at <10 days, and 6 received the stent-graft at 3 months. The macroporous cover did not prevent continued perfusion of the sac early after stent-graft deployment, but all aneurysms were excluded on the 1-month CT. CONCLUSIONS: Spontaneous AAA rupture occurred earlier and was not as frequent as previously described for this model. Implantation of the covered stent was feasible, but aneurysm exclusion was not immediate.

ALK-positive lymphoma: a single disease with a broad spectrum of morphology.

The t(2;5)(p23;q35) translocation, associated with anaplastic large-cell lymphoma (ALCL), results in the expression of a chimeric NPM-ALK protein that can be detected by the ALK1 monoclonal antibody. This report describes the morphologic and phenotypic spectrum of 123 cases of lymphoma that all express ALK protein. The results provide strong evidence that the morphologic patterns of ALCL described in previous reports as representing possible subtypes of ALCL, eg, common type, lymphohistiocytic, or small cell patterns, are morphologic variants of the same disease entity. All of these morphologic patterns could be found within this series, and in some patients different subtypes coexisted in a single biopsy or were found in successive biopsies from a single patient. The link between these morphologic subtypes is further reinforced by the presence in all cases of a highly characteristic large cell, with an eccentric nucleus and an eosinophilic paranuclear region. We suggest that this cell can be considered as a major distinguishing feature of ALK-positive lymphomas. Another characteristic of these tumors was the perivascular pattern of neoplastic cell infiltration seen in a significant number of cases. In addition to ALK protein, all tumors expressed epithelial membrane antigen and lacked CD15, features that may be of value in differentiating ALCL from Hodgkin's disease. In the majority of cases (84%), malignant cells showed both a cytoplasmic and nuclear staining for ALK1 and thus presumably carried the 2;5 translocation, but staining was restricted to the cytoplasm in a few cases, suggesting that translocations other than t(2;5) may induce expression of ALK protein. We conclude from this study that ALK-positive neoplasms represent a distinct entity. Because their morphology is often neither anaplastic nor large cell, we suggest that they should henceforward be referred to as ALK lymphomas.