A functional and structural comparative analysis of large tumor antigens reveals evolution of different importin α-dependent nuclear localization signals.

Nucleocytoplasmic transport regulates the passage of proteins between the nucleus and cytoplasm. In the best characterized pathway, importin (IMP) α bridges cargoes bearing basic, classical nuclear localization signals (cNLSs) to IMPß1, which mediates transport through the nuclear pore complex. IMPα recognizes three types of cNLSs via two binding sites: the major binding site accommodates monopartite cNLSs, the minor binding site recognizes atypical cNLSs, while bipartite cNLSs simultaneously interact with both major and minor sites. Despite the growing knowledge regarding IMPα-cNLS interactions, our understanding of the evolution of cNLSs is limited. We combined bioinformatic, biochemical, functional, and structural approaches to study this phenomenon, using polyomaviruses (PyVs) large tumor antigens (LTAs) as a model. We characterized functional cNLSs from all human (H)PyV LTAs, located between the LXCXE motif and origin binding domain. Surprisingly, the prototypical SV40 monopartite NLS is not well conserved; HPyV LTA NLSs are extremely heterogenous in terms of structural organization, IMPα isoform binding, and nuclear targeting abilities, thus influencing the nuclear accumulation properties of full-length proteins. While several LTAs possess bipartite cNLSs, merkel cell PyV contains a hybrid bipartite cNLS whose upstream stretch of basic amino acids can function as an atypical cNLS, specifically binding to the IMPα minor site upon deletion of the downstream amino acids after viral integration in the host genome. Therefore, duplication of a monopartite cNLS and subsequent accumulation of point mutations, optimizing interaction with distinct IMPα binding sites, led to the evolution of bipartite and atypical NLSs binding at the minor site.

Structural characterisation of hemagglutinin from seven Influenza A H1N1 strains reveal diversity in the C05 antibody recognition site.

Influenza virus (IV) causes several outbreaks of the flu each year resulting in an economic burden to the healthcare system in the billions of dollars. Several influenza pandemics have occurred during the last century and estimated to have caused 100 million deaths. There are four genera of IV, A (IVA), B (IVB), C (IVC), and D (IVD), with IVA being the most virulent to the human population. Hemagglutinin (HA) is an IVA surface protein that allows the virus to attach to host cell receptors and enter the cell. Here we have characterised the high-resolution structures of seven IVA HAs, with one in complex with the anti-influenza head-binding antibody C05. Our analysis revealed conserved receptor binding residues in all structures, as seen in previously characterised IV HAs. Amino acid conservation is more prevalent on the stalk than the receptor binding domain (RBD; also called the head domain), allowing the virus to escape from antibodies targeting the RBD. The equivalent site of C05 antibody binding to A/Denver/57 HA appears hypervariable in the other H1N1 IV HAs. Modifications within this region appear to disrupt binding of the C05 antibody, as these HAs no longer bind the C05 antibody by analytical SEC. Our study brings new insights into the structural and functional recognition of IV HA proteins and can contribute to further development of anti-influenza vaccines.

Importin α/ß-dependent nuclear transport of human parvovirus B19 nonstructural protein 1 is essential for viral replication.

Human parvovirus B19 (B19V) is a major human pathogen causing a variety of diseases, characterized by a selective tropism to human progenitor cells in bone marrow. In similar fashion to all Parvoviridae members, the B19V ssDNA genome is replicated within the nucleus of infected cells through a process which involves both cellular and viral proteins. Among the latter, a crucial role is played by non-structural protein (NS)1, a multifunctional protein involved in genome replication and transcription, as well as modulation of host gene expression and function. Despite the localization of NS1 within the host cell nucleus during infection, little is known regarding the mechanism of its nuclear transport pathway. In this study we undertake structural, biophysical, and cellular approaches to characterize this process. Quantitative confocal laser scanning microscopy (CLSM), gel mobility shift, fluorescence polarization and crystallographic analysis identified a short sequence of amino acids (GACHAKKPRIT-182) as the classical nuclear localization signal (cNLS) responsible for nuclear import, mediated in an energy and importin (IMP) α/ß-dependent fashion. Structure-guided mutagenesis of key residue K177 strongly impaired IMPα binding, nuclear import, and viral gene expression in a minigenome system. Further, treatment with ivermectin, an antiparasitic drug interfering with the IMPα/ß dependent nuclear import pathway, inhibited NS1 nuclear accumulation and viral replication in infected UT7/Epo-S1 cells. Thus, NS1 nuclear transport is a potential target of therapeutic intervention against B19V induced disease.

The role of prophylactic aspirin intake in reducing the risk of development of preeclampsia among nonhigh-risk primigravidas in two tertiary hospitals in Dasmariñas and Imus, Cavite: A retrospective cohort study / Philippine Journal of Obstetrics and Gynecology

Background@#Pre-eclampsia is a multi-organ progressive disorder that is estimated to complicate 2 to 8% of pregnancies. Numerous studies on prophylactic aspirin intake among high-risk pregnant women has been established but studies involving low-risk primigravida women are limited.@*Objectives@#To determine if prophylactic intake of aspirin will reduce the occurrence of preeclampsia among primigravida women with no identified comorbidities and to determine the incidence and association of identified secondary outcomes.@*Methodology@#This retrospective cohort study was conducted from January 2018 to December 2020 in two (2) tertiary hospitals in the province of Cavite. Two hundred four (204) primigravida women with no identified co-morbidities and delivered to a singleton fetus, vaginally or operatively, were identified and included. In-patient and out-patient charts of primigravida women, with aspirin intake versus no aspirin intake, were reviewed. Primary outcome (pregnancy induced hypertension) and secondary outcomes (preterm delivery, small-for-gestational age infants, IUFD, HELLP syndrome and abruption placenta) were identified.@*Results@#The mean age of patients was 27.1 years and 25.9 years in the aspirin and non-aspirin group, respectively. In aspirin group, 4.9% of the patients developed pre-eclampsia versus 9.8% in non-aspirin group showing statistical significance. The effect of aspirin across other hypertensive disorders of pregnancy were noted to be the same. However, influence of aspirin with the average blood pressure on admission and secondary outcomes were not statistically significant.@*Conclusion@#CONCLUSION: Prophylactic aspirin intake has a significant effect in preventing pre-eclampsia among non-high risk primigravida women but did not influence the average blood pressure on admission, development of preterm PIH, and development of the secondary outcomes.

Generation of diverse neural cell types through direct conversion.

A characteristic of neurological disorders is the loss of critical populations of cells that the body is unable to replace, thus there has been much interest in identifying methods of generating clinically relevant numbers of cells to replace those that have been damaged or lost. The process of neural direct conversion, in which cells of one lineage are converted into cells of a neural lineage without first inducing pluripotency, shows great potential, with evidence of the generation of a range of functional neural cell types both in vitro and in vivo, through viral and non-viral delivery of exogenous factors, as well as chemical induction methods. Induced neural cells have been proposed as an attractive alternative to neural cells derived from embryonic or induced pluripotent stem cells, with prospective roles in the investigation of neurological disorders, including neurodegenerative disease modelling, drug screening, and cellular replacement for regenerative medicine applications, however further investigations into improving the efficacy and safety of these methods need to be performed before neural direct conversion becomes a clinically viable option. In this review, we describe the generation of diverse neural cell types via direct conversion of somatic cells, with comparison against stem cell-based approaches, as well as discussion of their potential research and clinical applications.

Direct Conversion of Equine Adipose-Derived Stem Cells into Induced Neuronal Cells Is Enhanced in Three-Dimensional Culture.

The ability to culture neurons from horses may allow further investigation into equine neurological disorders. In this study, we demonstrate the generation of induced neuronal cells from equine adipose-derived stem cells (EADSCs) using a combination of lentiviral vector expression of the neuronal transcription factors Brn2, Ascl1, Myt1l (BAM) and NeuroD1 and a defined chemical induction medium, with ßIII-tubulin-positive induced neuronal cells displaying a distinct neuronal morphology of rounded and compact cell bodies, extensive neurite outgrowth, and branching of processes. Furthermore, we investigated the effects of dimensionality on neuronal transdifferentiation, comparing conventional two-dimensional (2D) monolayer culture against three-dimensional (3D) culture on a porous polystyrene scaffold. Neuronal transdifferentiation was enhanced in 3D culture, with evenly distributed cells located on the surface and throughout the scaffold. Transdifferentiation efficiency was increased in 3D culture, with an increase in mean percent conversion of more than 100% compared to 2D culture. Additionally, induced neuronal cells were shown to transit through a Nestin-positive precursor state, with MAP2 and Synapsin 2 expression significantly increased in 3D culture. These findings will help to increase our understanding of equine neuropathogenesis, with prospective roles in disease modeling, drug screening, and cellular replacement for treatment of equine neurological disorders.

A paper-based scaffold for enhanced osteogenic differentiation of equine adipose-derived stem cells.

OBJECTIVES: We investigated the applicability of single layer paper-based scaffolds for the three-dimensional (3D) growth and osteogenic differentiation of equine adipose-derived stem cells (EADSC), with comparison against conventional two-dimensional (2D) culture on polystyrene tissue culture vessels. RESULTS: Viable culture of EADSC was achieved using paper-based scaffolds, with EADSC grown and differentiated in 3D culture retaining high cell viability (>94 %), similarly to EADSC in 2D culture. Osteogenic differentiation of EADSC was significantly enhanced in 3D culture, with Alizarin Red S staining and quantification demonstrating increased mineralisation (p < 0.0001), and an associated increase in expression of the osteogenic-specific markers alkaline phosphatase (p < 0.0001), osteopontin (p < 0.0001), and runx2 (p < 0.01). Furthermore, scanning electron microscopy revealed a spherical morphology of EADSC in 3D culture, compared to a flat morphology of EADSC in 2D culture. CONCLUSIONS: Single layer paper-based scaffolds provide an enhanced environment for the in vitro 3D growth and osteogenic differentiation of EADSC, with high cell viability, and a spherical morphology.

Efficient transduction of equine adipose-derived mesenchymal stem cells by VSV-G pseudotyped lentiviral vectors.

Equine adipose-derived mesenchymal stem cells (EADMSC) provide a unique cell-based approach for treatment of a variety of equine musculoskeletal injuries, via regeneration of diseased or damaged tissue, or the secretion of immunomodulatory molecules. These capabilities can be further enhanced by genetic modification using lentiviral vectors, which provide a safe and efficient method of gene delivery. We investigated the suitability of lentiviral vector technology for gene delivery into EADMSC, using GFP expressing lentiviral vectors pseudotyped with the G glycoprotein from the vesicular stomatitis virus (V-GFP) or, for the first time, the baculovirus gp64 envelope protein (G-GFP). In this study, we produced similarly high titre V-GFP and G-GFP lentiviral vectors. Flow cytometric analysis showed efficient transduction using V-GFP; however G-GFP exhibited a poor ability to transduce EADMSC. Transduction resulted in sustained GFP expression over four passages, with minimal effects on cell viability and doubling time, and an unaltered chondrogenic differentiation potential.

Guillain-Barré syndrome and its variants: a case of acute motor-sensory axonal neuropathy in Jamaica / Síndrome de Guillain-Barré y sus variantes: un caso de la neuropatía axonal sensorial motor aguda en Jamaica

This paper reports a case of a Jamaican young woman who experienced flaccid quadriparesis and bulbar weakness over a three-week period after a gastrointestinal illness. Nerve conduction studies confirmed an axonal type neuropathy consistent with the acute motor-sensory axonal neuropathy variant of the Guillain-Barré syndrome. Recovery, although evident, was slow and was augmented after a course of intravenous immunoglobulin. The patient was discharged from hospital after three months but was re-admitted one week later and eventually succumbed to complications of the illness. This case serves as a reminder that Guillain-Barré syndrome is now the most common cause of acute flaccid paralysis and should be considered early in all patients presenting with flaccid quadriparesis.

El presenta trabajo reporta el caso de una joven jamaicana que experimentó debilidad bulbar y cuadriparesiaflácida por un período de tres semanas después de una enfermedad gastrointestinal. Los estudios de conducción nerviosa confirmaron una neuropatía de tipo axonal en correspondencia con la variante de la neuropatía axonal sensorial motora aguda del síndrome de Guillain-Barré. La recuperación, aunque evidente, fue lenta, y aumentó después de que se le aplicara inmunoglobulina intravenosa. La paciente fue dada de alta del hospital después de tres meses, pero fue ingresada de nuevo una semana más tarde, falleciendo finalmente a causa de las complicaciones de la enfermedad. Este caso sirve como recordatorio de que el síndrome de Guillain-Barré es ahora la causa más común de parálisis flácida aguda, y debe tenerse en cuenta temprano en todos los pacientes que acuden con cuadriparesia flácida.

Guillain-Barré syndrome and its variants: a case of acute motor-sensory axonal neuropathy in Jamaica.

This paper reports a case of a Jamaican young woman who experienced flaccid quadriparesis and bulbar weakness over a three-week period after a gastrointestinal illness. Nerve conduction studies confirmed an axonal type neuropathy consistent with the acute motor-sensory axonal neuropathy variant of the Guillain-Barré syndrome. Recovery, although evident, was slow and was augmented after a course of intravenous immunoglobulin. The patient was discharged from hospital after three months but was re-admitted one week later and eventually succumbed to complications of the illness. This case serves as a reminder that Guillain-Barré syndrome is now the most common cause of acute flaccid paralysis and should be considered early in all patients presenting with flaccid quadriparesis.

Quality of life of patients with epilepsy living in Kingston, Jamaica.

Quality of life in epilepsy has not been documented in the English-speaking Caribbean. The aim of this study was to explore the quality of life of persons with epilepsy (PWE) living in Jamaica and determine the impact of socioeconomic factors by examining two socially distinct groups in semiprivate (Epilepsy Centre of Jamaica) and public (Kingston Public Hospital) outpatient clinics. One hundred nine consecutive patients were interviewed. Quality of life was assessed using the Quality of Life in Epilepsy-31 inventory (QOLIE-31). Both groups were matched for gender, epilepsy syndrome, epilepsy duration, and number of antiepileptic drugs. Predictors of quality of life included number of antiepileptic drugs (P=0.039), epilepsy duration (P<0.05), and functional status (P<0.001). Neither seizure frequency nor socioeconomic status predicted QOLIE-31 scores. Mean QOLIE-31 total score (61.57 vs 49.2, P<0.001) and QOLIE-31 subscale scores (with the exception of the Seizure Worry score [53.8 vs 48.2, P=0.08]) were significantly higher than the corresponding t scores. The QOLIE-31 can reliably be used in Jamaica. Our findings suggest Jamaicans living with epilepsy perceive themselves as having a better than expected quality of life.

Quality of life in end stage renal disease: a multicentre comparative study / Calidad de vida en la etapa terminal de la enfermedad renal: un estudio comparativo multicéntrico

BACKGROUND: Quality of Life (QOL) in patients with End Stage Renal Disease (ESRD) is an important measure of dialysis adequacy. Health related QOL is an independent risk factor for mortality in ESRD. The Kidney Disease QOL questionnaire is a highly validated disease targeted instrument with global application. We sought to document QOL and the predictive factors in a cohort of patients with ESRD in Jamaica and Panama. METHODS: Two hundred patients were recruited consecutively from November 2006 - November 2007. Seventy patients were from a tertiary hospital based outpatient dialysis centre, the University Hospital of the West Indies (UHWI), and 40 patients from a private centre, Diabetes Association Renal Unit (DARU) both in Kingston, Jamaica. Ninety patients were consecutively recruited from a tertiary hospital based outpatient dialysis centre in Panama City, Panama. The Kidney Disease Quality of Life - Short Form Questionnaire was administered. Each QOL domain was scored from 0 - 100 with higher scores representing better rating. RESULTS: Mean age was 50 ± 4 years, with no difference between the cohorts. Panama, however, had significantly higher parameters than the Jamaican cohorts: mean haemoglobin (Hb) 12.4g/dL (p = 0.004), mean serum albumin 45g/dL (p = 0.03) and Urea Reduction Ratio (URR) 78% (p = 0.004). Diabetes Association Renal Unit recorded mean Hb 11.4 ± 1.3g/dL, mean serum albumin 42.1 ± 2.3g/dL and URR 72%. The University Hospital of the West Indies documented mean Hb 11.2 ± 2.4g/dL, mean serum albumin 41 ± 4.5g/dL and URR 68%. All three cohorts had good overall QOL scores when compared with the reference population. Patients from Panama had higher overall QOL scores than Jamaican patients (p = 0.02). By centre, UHWI had higher overall QOL scores than DARU (p = 0.04). Burden of Kidney Disease domain recorded the lowest overall scores (Reference Population 49, DARU 19.0 (p = 0.001), UHWI 24.0 (p = 0.002), Panama 32.9 (p = 0.03). Patient Satisfaction scores were also significantly reduced across all cohorts (Reference population 72, DARU 52, UHWI 54, Panama 58). The University Hospital of the West Indies had significantly decreased dialysis staff encouragement (p = 0.003). The Diabetes Association Renal Unit noted significant reductions in general health (p = 0.04), physical functioning (p = 0.001), physical role (p = 0.001) and emotional role (p = 0.005) domains. Panama had the lowest overall physical functioning (p = 0.01), pain (p = 0.01) and social support (p = 0.04) scores. In the Panamanian cohort, age < 65 years (p = 0.0004). Hb > 11.1 g/dL (p = 0.01), albumin > 40 g/dL (p = 0.01), URR > 65% (p = 0.03), race (p = 0.04), at least high school educational attainment (p = 0.01) and household yearly salaries > US$5000 (p = 0.002) predicted good QOL scores. These accounted for 55% of the variance. In the Jamaican cohort, however, younger age (p = 0.02), race (p = 0.001), higher URR (p = 0.01) and higher serum haemoglobin (p = 0.001) predicted higher QOL scores, accounting for only 40% of the variance. By modality, haemodialysis patients had significantly higher haemoglobin (p = 0.003) and albumin (p = 0.002) levels and ultimately higher overall QOL scores (p = 0.01). CONCLUSION: Overall, QOL is good in patients with ESRD. Domains of highest concern include Burden of Kidney Disease and Patient Satisfaction. The role of spirituality, depression and nutritional markers (eg prealbumin) needs to be assessed. Quality of Life must therefore be routinely documented in ESRD patients and targeted interventions implemented.

ANTECEDENTES: La calidad de vida (CDV) en los pacientes con enfermedad renal en etapa terminal (ERET) es un importante indicador de la medida en que la diálisis es adecuada. La CDV relacionada con la salud es un factor de riesgo independiente con respecto a la mortalidad en la ERET. El Cuestionario de Calidad de Vida en la Enfermedad Renal (KDQOL-SF) es un instrumento dirigido a la enfermedad, altamente validado y con aplicación global. Buscamos documentar la CDV y los factores predictivos en una cohorte de pacientes con ERET en Jamaica y Panamá. MÉTODOS: Se reclutaron doscientos pacientes consecutivamente de noviembre 2006 a noviembre 2007. Setenta pacientes provenían de un centro de diálisis para pacientes externos con base en un hospital terciario (HUWI) y 40 pacientes provenían de una Unidad Renal de la Asociación de Diabetes (DARU), ambas en Kingston, Jamaica. Otros noventa pacientes fueron reclutados consecutivamente de un centro de diálisis con base en un hospital de Ciudad Panamá. Se administró el Cuestionario de Calidad de Vida en la Enfermedad Renal (KDQOL-SF). Cada dominio de la CDV fue evaluado con una puntuación de 0 - 100, representando las puntuaciones más altas los mejores índices. RESULTADOS: La edad promedio fue de 50 ± 4 años, sin diferencias entre las cohortes. Sin embargo, Panamá tuvo parámetros significativamente más altos que las cohortes jamaicanas. El promedio de hemoglobina (Hb) fue 12.4g/dL (p = 0.004), el promedio de albúmina sérica 45g/dL (p = 0.03) y hubo una relación de reducción de la urea (URR) del 78% (p = 0.004). La Unidad Renal de Asociación de Diabetes registró un promedio de Hb de 11.4 ± 1.3 g/dL, y un promedio de albúmina sérica de 42.1 ± 2.3 g/dL en tanto que la URR fue 72%. El Hospital Universitario de West Indies documentó un promedio de Hb igual a 11.2 ± 2.4g/dL, una albúmina sérica promedio de 41 ± 4.5g/dL, y una URR de 68%. Las tres cohortes tuvieron buenas puntuaciones generales de CDV cuando se les comparó con la población de referencia. Los pacientes de Panamá tuvieron puntuaciones de CDV más altas que los pacientes jamaicanos (p = 0.02). En cuanto a centros, HUWI tuvo puntuaciones generales de CDV más altas que DARU (p = 0.04). El dominio de la sobrecarga de la enfermedad renal registró las puntuaciones generales más bajas (población de referencia 49, DARU 19.0 (p = 0.001), UHWI 24.0 (p = 0.002), Panamá 32.9 (p = 0.03). Las puntuaciones con respecto a la satisfacción del paciente estuvieron también significativamente reducidas en todas las cohortes (población de referencia 72, DARU 52, HUWI 54, Panamá 58). El Hospital Universitario de West Indies tuvo una disminución significativa del estímulo del personal de diálisis (p = 0.003). La Unidad Renal de la Asociación de Diabetes registró reducciones significativas en los dominios de la salud general (p = 0.04), el funcionamiento físico (p = 0.001), el rol físico (p = 0.001) y el rol emocional (p = 0.005). Panamá tuvo las puntuaciones más bajas en relación con el funcionamiento físico general (p = 0.01), el dolor (p = 0.01) y el apoyo social (p = 0.04). En la cohorte panameña, la edad < 65 años (p = 0.0004), la Hb > 11.1 g/dL (p = 0.01), la albúmina > 40g/dL (p = 0.01), la URR > 65% (p = 0.03), la raza (p = 0.04), el grado de escolaridad de nivel secundario al menos (p = 0.01) y los ingresos salariales domésticos por año > US$5000 (p = 0.002) arrojaron una buena predicción de la CDV. Estos representaban el 55% de la varianza. Sin embargo, en la cohorte jamaicana, una menor edad (p = 0.02), la raza (p = 0.001), una más alta URR (p = 0.01) y mayor hemoglobina sérica (p = 0.001) predijeron puntuaciones más altas de CDV, representando solamente 40% de la varianza. En cuanto a la modalidad, los pacientes de hemodiálisis tuvieron niveles de hemoglobina (p = 0.003) y albúmina (p = 0.002) significativamente más altos, y finalmente puntuaciones generales más alta de CDV (p = 0.01). CONCLUSIÓN: La CDV general es buena en los pacientes con ERET. Los dominios de mayor preocupación comprenden la recarga de la enfermedad renal y la satisfacción del paciente. El papel de la espiritualidad, la depresión y los marcadores nutricionales como la prealbúmina, necesitan ser evaluados. Por tanto, la calidad de vida tiene que ser documentada a modo de rutina entre los pacientes con ERET, y es necesario implementar intervenciones dirigidas.

Quality of life in end stage renal disease: a multicentre comparative study.

BACKGROUND: Quality of Life (QOL) in patients with End Stage Renal Disease (ESRD) is an important measure of dialysis adequacy. Health related QOL is an independent risk factor for mortality in ESRD. The Kidney Disease QOL questionnaire is a highly validated disease targeted instrument with global application. We sought to document QOL and the predictive factors in a cohort of patients with ESRD in Jamaica and Panama. METHODS: Two hundred patients were recruited consecutively from November 2006 - November 2007. Seventy patients were from a tertiary hospital based outpatient dialysis centre, the University Hospital of the West Indies (UHWI), and 40 patients from a private centre, Diabetes Association Renal Unit (DARU) both in Kingston, Jamaica. Ninety patients were consecutively recruited from a tertiary hospital based outpatient dialysis centre in Panama City, Panama. The Kidney Disease Quality of Life - Short Form Questionnaire was administered. Each QOL domain was scored from 0 - 100 with higher scores representing better rating. RESULTS: Mean age was 50 +/- 4 years, with no difference between the cohorts. Panama, however, had significantly higher parameters than the Jamaican cohorts: mean haemoglobin (Hb) 12.4g/dL (p = 0.004), mean serum albumin 45g/dL (p = 0.03) and Urea Reduction Ratio (URR) 78% (p = 0.004). Diabetes Association Renal Unit recorded mean Hb 11.4 +/- 1.3g/dL, mean serum albumin 42.1 +/- 2.3g/dL and URR 72%. The University Hospital of the West Indies documented mean Hb 11.2 +/- 2.4g/dL, mean serum albumin 41 +/- 4.5g/dL and URR 68%. All three cohorts had good overall QOL scores when compared with the reference population. Patients from Panama had higher overall QOL scores than Jamaican patients (p = 0.02). By centre, UHWI had higher overall QOL scores than DARU (p = 0.04). Burden of Kidney Disease domain recorded the lowest overall scores (Reference Population 49, DARU 19.0 (p = 0.001), UHWI 24.0 (p = 0.002), Panama 32.9 (p = 0.03). Patient Satisfaction scores were also significantly reduced across all cohorts (Reference population 72, DARU 52, UHWI 54, Panama 58). The University Hospital of the West Indies had significantly decreased dialysis staff encouragement (p = 0.003). The Diabetes Association Renal Unit noted significant reductions in general health (p = 0.04), physical functioning (p = 0.001), physical role (p = 0.001) and emotional role (p = 0.005) domains. Panama had the lowest overall physical functioning (p = 0.01), pain (p = 0.01) and social support (p = 0.04) scores. In the Panamanian cohort, age< 65 years (p = 0.0004). Hb > 11.1 g/dL (p = 0.01), albumin > 40g/dL (p = 0.01), URR > 65% (p = 0.03), race (p = 0.04), at least high school educational attainment (p = 0.01) and household yearly salaries > US$5000 (p = 0.002) predicted good QOL scores. These accounted for 55% of the variance. In the Jamaican cohort, however, younger age (p = 0.02), race (p = 0.001), higher URR (p = 0.01) and higher serum haemoglobin (p = 0.001) predicted higher QOL scores, accounting for only 40% of the variance. By modality, haemodialysis patients had significantly higher haemoglobin (p = 0.003) and albumin (p = 0.002) levels and ultimately higher overall QOL scores (p = 0.01). CONCLUSION: Overall, QOL is good in patients with ESRD. Domains of highest concern include Burden of Kidney Disease and Patient Satisfaction. The role of spirituality, depression and nutritional markers (eg prealbumin) needs to be assessed. Quality of Life must therefore be routinely documented in ESRD patients and targeted interventions implemented.

Steatohepatitis due to antiretroviral therapy / Esteatohepatitis debido a la terapia antiretroviral

Jamaica has recorded the largest increase in the rate of HIV/AIDS infection in the English-speaking Caribbean since 1985. Treatment has significantly improved recently with approximately 50% availability of antiretrovirals (ARVs) to patients. The incidence of drug induced hepatotoxicity is not well known for most ARV drugs and few studies have assessed adverse drug effects in clinical practice. A patient with HIV on highly active antiretroviral therapy (HAART) presented with a one year history of progressive abdominal distension. Abdominal examination revealed a 17 cm, smooth, non-tender liver with a rounded edge; 12 cm of which was below the right costal margin. Liver enzymes were grossly abnormal. The liver biopsy revealed parenchymal distortion by fibrosis with macrovesicular fatty change and Mallory's hyaline in keeping with steatohepatitis. Follow-up studies after discontinuation of stavudine revealed that the liver enzymes improved within four months. Physicians should be mindful of the hepatotoxic potential of ARVs and monitor liver enzymes in HIV-infected patients on therapy.

Jamaica ha registrado el mayor aumento de la tasa de infección de VIH/SIDA en el Caribe anglófono desde 1985. El tratamiento ha mejorado recientemente de manera significativa, con una disponibilidad de 50% de antiretrovirales (ARVs) para pacientes. La incidencia de la hepatotoxicidad inducida por medicamentos no es conocida para la mayoría de los medicamentos ARV y pocos estudios han evaluado los efectos adversos de esos medicamentos en la práctica clínica. Un paciente con VIH, sometido a una terapia antiretroviral altamente activa, se presentó con una historia de distensión abdominal progresiva de un año. El examen abdominal reveló un hígado de 17 cm, liso, no blando, y de bordes redondeados, 12 cm del cual se hallaban por debajo del margen del costado derecho. Las enzimas del hígado eran evidentemente anormales. La biopsia del hígado reveló una distorsión parenquimatosa por fibrosis con cambio graso macrovesicular y formación de hialina de Mallory en correspondencia con la esteatohepatitis. Los estudios de seguimiento tras la discontinuación de la estavudina, revelaron que las enzimas del hígado mejoraron en cuatro meses. Los médicos deben tomar conciencia del potencial hepatotóxico de los ARVs y monitorear las enzimas del hígado en pacientes infectados con el VIH que se hallen bajo terapia.

Steatohepatitis due to antiretroviral therapy.

Jamaica has recorded the largest increase in the rate of HIV/AIDS infection in the English-speaking Caribbean since 1985. Treatment has significantly improved recently with approximately 50% availability of antiretrovirals (ARVs) to patients. The incidence of drug induced hepatotoxicity is not well known for most ARV drugs and few studies have assessed adverse drug effects in clinical practice. A patient with HIV on highly active antiretroviral therapy (HAART) presented with a one year history of progressive abdominal distension. Abdominal examination revealed a 17 cm, smooth, non-tender liver with a rounded edge; 12 cm of which was below the right costal margin. Liver enzymes were grossly abnormal. The liver biopsy revealed parenchymal distortion by fibrosis with macrovesicular fatty change and Mallory's hyaline in keeping with steatohepatitis. Follow-up studies after discontinuation of stavudine revealed that the liver enzymes improved within four months. Physicians should be mindful of the hepatotoxic potential of ARVs and monitor liver enzymes in HIV-infected patients on therapy.

Effect of breast magnetic resonance imaging on the clinical management of women with early-stage breast carcinoma.

PURPOSE: To determine the impact of breast magnetic resonance imaging (MRI) on the clinical management of patients with early-stage breast cancer. PATIENTS AND METHODS: A review was performed of the records of 207 women with early-stage breast cancer (including five women with bilateral disease) who underwent breast MRI during work-up for breast conservation treatment. All patients presented with clinical stage 0, I, or II disease. For each patient, a determination was made whether the breast MRI affected the clinical management, and if so, whether the patient was well served by the change in management. RESULTS: The MRI findings affected the clinical management in 43 cases (20% of 212 breast cancers). Based on the pathology findings and the overall clinical course for each case, the breast MRI was judged to have had a strongly favorable effect on management in 18 cases (8%), a somewhat favorable effect in six cases (3%), an uncertain effect in five cases (2%), a somewhat unfavorable effect in 11 cases (5%), and a strongly unfavorable effect in three cases (1%). The effect of MRI was not significantly different for invasive carcinoma compared with ductal carcinoma-in-situ (all P > or =.27). However, the effect of MRI was significantly greater when the MRI was performed before an excisional biopsy (P =.0011) or for larger tumors (P =.0089). CONCLUSIONS: Breast MRI alters the clinical management for a sizable fraction of women with early-stage breast cancer and appears to offer clinically useful information for determining optimal local treatment.

Electron Diffraction Using Transmission Electron Microscopy.

Electron diffraction via the transmission electron microscope is a powerful method for characterizing the structure of materials, including perfect crystals and defect structures. The advantages of electron diffraction over other methods, e.g., x-ray or neutron, arise from the extremely short wavelength (≈2 pm), the strong atomic scattering, and the ability to examine tiny volumes of matter (≈10 nm(3)). The NIST Materials Science and Engineering Laboratory has a history of discovery and characterization of new structures through electron diffraction, alone or in combination with other diffraction methods. This paper provides a survey of some of this work enabled through electron microscopy.

Precipitation hardening in the first aerospace aluminum alloy: the wright flyer crankcase.

Aluminum has had an essential part in aerospace history from its very inception: An aluminum copper alloy (with a copper composition of 8 percent by weight) was used in the engine that powered the historic first flight of the Wright brothers in 1903. Examination of this alloy shows that it is precipitation-hardened by Guinier-Preston zones in a bimodal distribution, with larger zones (10 to 22 nanometers) originating in the casting practice and finer ones (3 nanometers) resulting from ambient aging over the last 90 years. The precipitation hardening in the Wright Flyer crankcase occurred earlier than the experiments of Wilm in 1909, when such hardening was first discovered, and predates the accepted first aerospace application of precipitation-hardened aluminum in 1910.