Normal transaminases in obese patients with metabolic associated steatohepatitis (MASH): a cohort of Peruvian patients.

INTRODUCTION: Metabolic associated steatohepatitis (MASH) is one of the most frequent causes of chronic liver disease. Liver transaminases are important biomarkers to measure liver injury, however, a proportion of patients with MASH may present with normal levels of transaminases. The levels of serum transaminases may not correlate with the severity of histopathological changes. OBJECTIVE: We aimed to identify the frequency of normal transaminases in obese patients with MASH, as well as to describe the clinical, biochemical and histological characteristics in this specific group of patients. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted in the bariatric surgery service of a private clinic. Obese patients older than 18 years with a body mass index (BMI) >30Kg/m2 and 2 co-morbidities undergoing a gastric sleeve surgery were included. Measurement of biochemical routine laboratory exams was performed. Insulin resistance was calculated using the homeostasis evaluation model (HOMA-IR). All patients underwent liver biopsies prior to surgery and the diagnosis of MASH was based on the Brunt criteria. RESULTS: 159 obese patients with MASH were included, of which 47.2% had normal transaminases and 52.8% elevated transaminases. Factors associated with alteration in transaminases were: being male OR=4.02 (95% CI: 2.03- 7.96; p<0.01), diagnosis of type 2 diabetes mellitus OR=4.86 (95% CI: 1.97- 11.95; p<0.01) and levels of GGT >50 IU/L OR=7.50 (95% CI: 3.40-16.56; p<0.01). The values of HOMA-IR and GGT were significantly higher in the group of high transaminases (p<0.01). Differences in the degree of fibrosis were not associated with transaminases levels. CONCLUSION: In conclusion we found that the frequency of normal transaminases was 47.2% in obese patients with MASH. Factors associated with elevation in liver enzymes were being male, diagnosis of diabetes mellitus and elevation in GGT levels. The degree of fibrosis was not associated with elevations in liver transaminases. These findings suggest that transaminases levels alone are not accurate markers to assess liver injury, as they do not necessarily correlate with histological liver damage.

Normal transaminases in obese patients with metabolic associated steatohepatitis (MASH): a cohort of Peruvian patients

Introduction: Metabolic associated steatohepatitis (MASH) is one of the most frequent causes of chronic liver disease. Liver transaminases are important biomarkers to measure liver injury, however, a proportion of patients with MASH may present with normal levels of transaminases. The levels of serum transaminases may not correlate with the severity of histopathological changes. Objective: We aimed to identify the frequency of normal transaminases in obese patients with MASH, as well as to describe the clinical, biochemical and histological characteristics in this specific group of patients. Materials and methods: A retrospective cross-sectional study was conducted in the bariatric surgery service of a private clinic. Obese patients older than 18 years with a body mass index (BMI) >30Kg/m2 and 2 co-morbidities undergoing a gastric sleeve surgery were included. Measurement of biochemical routine laboratory exams was performed. Insulin resistance was calculated using the homeostasis evaluation model (HOMA-IR). All patients underwent liver biopsies prior to surgery and the diagnosis of MASH was based on the Brunt criteria. Results: 159 obese patients with MASH were included, of which 47.2% had normal transaminases and 52.8% elevated transaminases. Factors associated with alteration in transaminases were: being male OR=4.02 (95% CI: 2.037.96; p50 IU/L OR=7.50 (95% CI: 3.40-16.56; p<0.01). The values of HOMA-IR and GGT were significantly higher in the group of high transaminases (p<0.01). Differences in the degree of fibrosis were not associated with transaminases levels. Conclusion: In conclusion we found that the frequency of normal transaminases was 47.2% in obese patients with MASH. Factors associated with elevation in liver enzymes were being male, diagnosis of diabetes mellitus and elevation in GGT levels. The degree of fibrosis was not associated with elevations in liver transaminases. These findings suggest that transaminases levels alone are not accurate markers to assess liver injury, as they do not necessarily correlate with histological liver damage.

Introducción: La esteatohepatitis asociada metabólica (MASH) es una de las causas más frecuentes de enfermedad hepática crónica. Las transaminasas hepáticas son biomarcadores importantes para medir el daño hepático; sin embargo, una proporción de pacientes con MASH pueden presentar niveles normales de transaminasas. Los niveles de transaminasas séricas pueden no estar correlacionados con la gravedad de los cambios histopatológicos. Objetivo: Nuestro objetivo fue identificar la frecuencia de transaminasas normales en pacientes obesos con MASH, así como describir las características clínicas, bioquímicas e histológicas en este grupo específico de pacientes. Materiales y métodos: Se realizó un estudio transversal retrospectivo en el servicio de cirugía bariátrica de una clínica privada. Se incluyeron pacientes obesos mayores de 18 años con índice de masa corporal (IMC) >30Kg/m2 y 2 comorbilidades sometidos a cirugía de manga gástrica. Se realizó la medición de los exámenes bioquímicos de laboratorio de rutina. La resistencia a la insulina se calculó mediante el modelo de evaluación de la homeostasis (HOMA-IR). Todos los pacientes se sometieron a biopsias hepáticas antes de la cirugía y el diagnóstico de MASH se basó en los criterios de Brunt. Resultados: Se incluyeron 159 pacientes obesos con MASH, de los cuales el 47,2% tenían transaminasas normales y el 52,8% transaminasas elevadas. Los factores asociados a la alteración de las transaminasas fueron: ser hombre OR=4,02 (IC 95%: 2,03-7,96; p50 UI/L OR=7,50 (IC 95%: 3,40-16,56; p<0,01). Los valores de HOMA-IR y GGT fueron significativamente mayores en el grupo de transaminasas altas (p<0,01). Las diferencias en el grado de fibrosis no se asociaron con los niveles de transaminasas. Conclusión: Encontramos que la frecuencia de transaminasas normales fue del 47,2% en pacientes obesos con MASH. Los factores asociados con la elevación de las enzimas hepáticas fueron el sexo masculino, el diagnóstico de diabetes mellitus y la elevación de los niveles de GGT. El grado de fibrosis no se asoció con elevaciones de las transaminasas hepáticas. Estos hallazgos sugieren que los niveles de transaminasas por sí solos no son marcadores precisos para evaluar el daño hepático, ya que no necesariamente se correlacionan con el daño hepático histológico.

Alternative splicing of coq-2 controls the levels of rhodoquinone in animals.

Parasitic helminths use two benzoquinones as electron carriers in the electron transport chain. In normoxia, they use ubiquinone (UQ), but in anaerobic conditions inside the host, they require rhodoquinone (RQ) and greatly increase RQ levels. We previously showed the switch from UQ to RQ synthesis is driven by a change of substrates by the polyprenyltransferase COQ-2 (Del Borrello et al., 2019; Roberts Buceta et al., 2019); however, the mechanism of substrate selection is not known. Here, we show helminths synthesize two coq-2 splice forms, coq-2a and coq-2e, and the coq-2e-specific exon is only found in species that synthesize RQ. We show that in Caenorhabditis elegans COQ-2e is required for efficient RQ synthesis and survival in cyanide. Importantly, parasites switch from COQ-2a to COQ-2e as they transit into anaerobic environments. We conclude helminths switch from UQ to RQ synthesis principally via changes in the alternative splicing of coq-2.

An isomerase completes the circuit for a redox switch.

The activity of human transglutaminase 2 (TG2), which forms protein cross-links between glutamine and lysine residues, is controlled by an allosteric disulfide bond. However, the mechanism by which this bond is formed, like many systems regulated by oxidative cysteine modifications, was not clear. A new study from Khosla and colleagues shows that TG2 is oxidatively inactivated by the protein disulfide isomerase ERp57, providing the first example of a defined and reversible protein-controlled redox switch and pointing to new strategies to inhibit undesirable TG2 activity in pathological states.

Alternative Thiol-Based Redox Systems.

The maintenance of thiol-redox homeostasis is vital to the survival of living organisms. Sulfur-based low-molecular weight compounds and proteins synthesized by cells provide efficient and specific ways to counteract oxidative stress and regulate cellular processes. For these tasks, most organisms share the glutathione and thioredoxin NADPH-dependent redox systems. However, in certain lineages, evolution has taken different paths that led to the emergence of novel cysteine-based low-molecular weight redox cofactors, around which new redox systems evolved. These include the sugar-based cysteinyl derivatives mycothiol and bacillithiol, and ergothioneine (EGT), which are present in different phyla from bacteria. Within Eukarya, some fungi contain EGT, whereas trypanothione is unique to species from the Euglenozoa family. This Forum compiles the state-of-the-art knowledge about these noncanonical redox systems of pathogenic organisms. The functions in physiology and pathogenicity, as well as structural and biochemical specializations that these system components evolved, are thoroughly discussed. Antioxid. Redox Signal. 28, 407-409.

The Enzymatic and Structural Basis for Inhibition of Echinococcus granulosus Thioredoxin Glutathione Reductase by Gold(I).

AIMS: New drugs are needed to treat flatworm infections that cause severe human diseases such as schistosomiasis. The unique flatworm enzyme thioredoxin glutathione reductase (TGR), structurally different from the human enzyme, is a key drug target. Structural studies of the flatworm Echinococcus granulosus TGR, free and complexed with AuI-MPO, a novel gold inhibitor, together with inhibition assays were performed. RESULTS: AuI-MPO is a potent TGR inhibitor that achieves 75% inhibition at a 1:1 TGR:Au ratio and efficiently kills E. granulosus in vitro. The structures revealed salient insights: (i) unique monomer-monomer interactions, (ii) distinct binding sites for thioredoxin and the glutaredoxin (Grx) domain, (iii) a single glutathione disulfide reduction site in the Grx domain, (iv) rotation of the Grx domain toward the Sec-containing redox active site, and (v) a single gold atom bound to Cys519 and Cys573 in the AuI-TGR complex. Structural modeling suggests that these residues are involved in the stabilization of the Sec-containing C-terminus. Consistently, Cys→Ser mutations in these residues decreased TGR activities. Mass spectroscopy confirmed these cysteines are the primary binding site. INNOVATION: The identification of a primary site for gold binding and the structural model provide a basis for gold compound optimization through scaffold adjustments. CONCLUSIONS: The structural study revealed that TGR functions are achieved not only through a mobile Sec-containing redox center but also by rotation of the Grx domain and distinct binding sites for Grx domain and thioredoxin. The conserved Cys519 and Cys573 residues targeted by gold assist catalysis through stabilization of the Sec-containing redox center. Antioxid. Redox Signal. 27, 1491-1504.

Selenoprotein T is required for pathogenic bacteria avoidance in Caenorhabditis elegans.

Selenoprotein T (SELENOT) is an endoplasmatic reticulum (ER)-associated redoxin that contains the amino acid selenocysteine (Sec, U) within a CXXU motif within a thioredoxin-like fold. Its precise function in multicellular organisms is not completely understood although it has been shown in mammals to be involved in Ca2+ homeostasis, antioxidant and neuroendocrine functions. Here, we use the model organism C. elegans to address SELENOT function in a whole organism throughout its life cycle. C. elegans possess two genes encoding SELENOT protein orthologues (SELT-1.1 and SELT-1.2), which lack Sec and contain the CXXC redox motif instead. Our results show that a Sec→Cys replacement and a gene duplication were two major evolutionary events that occurred in the nematode lineage. We find that worm SELT-1.1 localizes to the ER and is expressed in different cell types, including the nervous system. In contrast, SELT-1.2 exclusively localizes in the cytoplasm of the AWB neurons. We find that selt-1.1 and selt-1.2 single mutants as well as the double mutant are viable, but the selt-1.1 mutant is compromised under rotenone-induced oxidative stress. We demonstrate that selt-1.1, but not selt-1.2, is required for avoidance to the bacterial pathogens Serratia marcescens and Pseudomonas aeruginosa. Aversion to the noxious signal 2-nonanone is also significantly impaired in selt-1.1, but not in selt-1.2 mutant animals. Our results suggest that selt-1.1 would be a redox transducer required for nociception and optimal organismal fitness. The results highlight C. elegans as a valuable model organism to study SELENOT-dependent processes.

Del Nido cardioplegia in low risk adults undergoing first time coronary artery bypass surgery.

OBJECTIVES: Single-dose del Nido cardioplegia has been used in the pediatric population for many years. Only a small amount of data exists about its use in adult cardiac surgery. We sought to compare the outcomes of all patients undergoing coronary artery bypass, using our 4:1 blood cardioplegia versus single-dose 1:4 del Nido cardioplegia, at our institution. METHODS: Data were retrospectively reviewed from all patients during 2 consecutive years (2013-2014). We switched our cardioplegia protocol from 4:1 blood cardioplegia to exclusively 1:4 single-dose del Nido cardioplegia in early 2014. A total of 408 patients were evaluated. Two hundred and forty-nine consecutive patients underwent coronary artery bypass using blood cardioplegia and 159 using del Nido Cardioplegia. RESULTS: Cardiopulmonary bypass time, cross-clamp time, in-hospital mortality and length of stay were similar (p>0.05): 63 ± 23 vs. 65 ± 21 min, 50 ± 20 vs. 52 ± 20 min, 0.8% vs. 0.6% and 6.4 ± 3 vs. 5.8 ± 3 days, respectively. For secondary outcomes: patients requiring defibrillation was 105/249 (42%) vs. 13/159 (8%) (p<0.0001), blood transfusion was required in 96/249 (38%) vs. 48/159 (30%) (p<0.085), total volume administered was 1139mL vs. 813 mL per case (p<0.0001), hematocrit change was 11.6% vs. 10.9% (p<0.04) and the mean cost per dose was $157.54 vs $5.74. CONCLUSIONS: Single-dose del Nido cardioplegia is an effective and economic cardioplegia and can be used with good outcomes in coronary surgery. Most patients have spontaneous return of sinus rhythm and there is a trend towards decreased transfusion rate.

Aplicaciones de la toxina botulínica en afecciones palpebrales / Uses of botulinum toxin in eyelid diseases

La toxina botulínica es un potente inhibidor neuromuscular altamente específico que produce una denervación química al bloquear la liberación de acetilcolina en la placa motora. Es sintetizada por Clostridium botulinum. Es un fármaco de alto valor terapéutico en las alteraciones de los anexos oculares; puede indicarse con muy buenos resultados en afecciones como el blefarospasmo primario, el espasmo hemifacial, el chalazión, el entropion espasmódico, la retracción palpebral, la ptosis de la ceja, la mioquimia palpebral y en el tratamiento de líneas de expresión facial, con muy buenos resultados estéticos. Se realizó una búsqueda bibliográfica y en Internet utilizando distintas bases de datos como Medline, Google, Bireme, PubMed.gov, así como artículos relevantes de la Academia americana de Oftalmología y Neurología con el objetivo de describir las aplicaciones de la neurotóxica botulínica en las afecciones de los anexos oculares(AU)

Botulinum toxin is a highly specific potent neuromuscular inhibitor that produces a chemical denervation when blocking the release of acetylcholine in the motor plaque. It is synthesized by clostridium botulinum. It is a drug with high therapeutic value to treat ocular adnexas and may be indicated for primary blepharospasm, hemifacial spasm, chalazion, spasmodic entropion, palpebral retraction, eye brow ptosis, palpebral myokymia and in treating expression lines of the face, all with very good esthetic results. Literature search was made in Internet by using databases such as Medline, Google, Bireme, PubMed.gov, as well as outstanding articles of the American Academy of Ophthalmology and Neurology with the objective of describing the uses of botulinum toxin for ocular adnexa diseases(AU)

Selenoproteins of African trypanosomes are dispensable for parasite survival in a mammalian host.

The trace element selenium is found in polypeptides as selenocysteine, the 21(st) amino acid that is co-translationally inserted into proteins at a UGA codon. In proteins, selenocysteine usually plays a role as an efficient redox catalyst. Trypanosomatids previously examined harbor a full set of genes encoding the machinery needed for selenocysteine biosynthesis and incorporation into three selenoproteins: SelK, SelT and, the parasite-specific, Seltryp. We investigated the selenoproteome of kinetoplastid species in recently sequenced genomes and assessed the in vivo relevance of selenoproteins for African trypanosomes. Database mining revealed that SelK, SelT and Seltryp genes are present in most kinetoplastids, including the free-living species Bodo saltans, and Seltryp was lost in the subgenus Viannia from the New World Leishmania. Homology and sinteny with bacterial sulfur dioxygenases and sulfur transferases suggest a putative role for Seltryp in sulfur metabolism. A Trypanosoma brucei selenocysteine synthase (SepSecS) null-mutant, in which selenoprotein synthesis is abolished, displayed similar sensitivity to oxidative stress induced by a short-term exposure to high concentrations of methylglyoxal or H2O2 to that of the parental wild-type cell line. Importantly, the infectivity of the SepSecS knockout cell line was not impaired when tested in a mouse infection model and compensatory effects via up-regulation of proteins involved in thiol-redox metabolism were not observed. Collectively, our data show that selenoproteins are not required for survival of African trypanosomes in a mammalian host and exclude a role for selenoproteins in parasite antioxidant defense and/or virulence. On this basis, selenoproteins can be disregarded as drug target candidates.

A New Class of Thioredoxin-Related Protein Able to Bind Iron-Sulfur Clusters.

AIMS: Members of the thioredoxin (Trx) protein family participate mainly in redox pathways and have not been associated with Fe/S binding, in contrast to some closely related glutaredoxins (Grxs). Cestode parasites possess an unusual diversity of Trxs and Trx-related proteins with unexplored functions. In this study, we addressed the biochemical characterization of a new class of Trx-related protein (IsTRP) and a classical monothiol Grx (EgGrx5) from the human pathogen Echinococcus granulosus. RESULTS: The dimeric form of IsTRP coordinates Fe2S2 in a glutathione-independent manner; instead, Fe/S binding relies on the CXXC motif conserved among Trxs. This novel binding mechanism allows holo-IsTRP to be highly resistant to oxidation. IsTRP lacks canonical reductase activities. Mitochondrially targeted IsTRP aids growth of a Grx5 null yeast strain. Similar complementation assays performed with EgGrx5 revealed functional conservation for class II Grxs, despite the presence of nonconserved structural elements. IsTRP is a cestode lineage-specific protein highly expressed in the gravid adult worm, which releases the infective stage critical for dissemination. INNOVATION: IsTRP is the first member from the Trx family to be reported to bind Fe/S. We disclose a novel mechanism of Fe/S coordination within the Trx folding unit, which renders the cluster highly resistant to oxidation-mediated disassembly. CONCLUSION: We demonstrate that IsTRP defines a new protein family within the Trx superfamily, confirm the conservation of function for class II Grx from nonphylogenetically related species, and highlight the versatility of the Trx folding unit to acquire Fe/S binding as a recurrent emergent function. Antioxid. Redox Signal. 00, 000-000.

Sarcoma de Kaposi en conjuntiva bulbar / Kaposi´s sarcoma in bulbar conjunctiva

Paciente masculino de 29 años de edad, raza blanca, soltero, profesor universitario, con antecedentes de padecer crisis de epilepsia tratado con fenitoína y actualmente controlado, menciona que desde hace aproximadamente 4 semanas comenzó con ojo rojo y molestias oculares del ojo derecho, por lo cual acudió a su área de salud donde fue tratado como cuadro de conjuntivitis. No mostró mejoría alguna, sino empeoramiento del cuadro clínico, y observó un enrojecimiento ocular intenso en el ángulo interno de dicho ojo que se fue extendiendo, acompañado de ligera fotofobia. Por la tórpida evolución del cuadro decidió acudir a nuestra institución por lo cual fue remitido a la Consulta de Oculoplastia. También refirió que desde hacía dos meses había presentado anorexia, dificultad al comer, así como pérdida de peso, por lo cual se decidió comenzar estudio y tratamiento. Se decidió realizar la resección de la masa tumoral en conjuntiva bulbar y se envió para estudio anatomopatológico. El resultado fue compatible con un sarcoma de Kaposi(AU)

A twenty-nine years-old male Caucasian patient, single and university professor, with a history of epilepsy treated with fenitoin and managed at present. He stated that 4 weeks ago approximately, he began feeling ocular discomfort in addition to reddened eye, so he went to his health area where he was treated as a conjunctivitis case. No improvement occurred, the clinical picture worsened and there was intensive ocular reddening in the internal angle of the eye that extended and mild photofobia. Because of the rapid profession of the clinical picture, he decided to go to our institution where he was referred to the Oculoplasty Service. He also said that he had been suffering anorexia, difficulties to eating and weight loss two months ago. It was then decided to start the study and treatment of this case. First, the tumor mass from the bulbar conjunctiva was resected and then sent to anatomical pathological study service. The result was compatible with Kaposi´s sarcoma diagnosis(AU)

Echinococcus granulosus antigen B: a Hydrophobic Ligand Binding Protein at the host-parasite interface.

Lipids are mainly solubilized by various families of lipid binding proteins which participate in their transport between tissues as well as cell compartments. Among these families, Hydrophobic Ligand Binding Proteins (HLBPs) deserve special consideration since they comprise intracellular and extracellular members, are able to bind a variety of fatty acids, retinoids and some sterols, and are present exclusively in cestodes. Since these parasites have lost catabolic and biosynthetic pathways for fatty acids and cholesterol, HLBPs are likely relevant for lipid uptake and transportation between parasite and host cells. Echinococcus granulosus antigen B (EgAgB) is a lipoprotein belonging to the HLBP family, which is very abundant in the larval stage of this parasite. Herein, we review the literature on EgAgB composition, structural organization and biological properties, and propose an integrated scenario in which this parasite HLBP contributes to adaptation to mammalian hosts by meeting both metabolic and immunomodulatory parasite demands.

Cirugía de blefaroplastia por técnica convencional versus láser de CO2 / Blepharoplasty with conventional technique versus CO2 laser

Objetivo: presentar los resultados de la cirugía de blefaroplastia, con la técnica convencional y con el uso del láser de CO2. Método: se realizó un estudio descriptivo longitudinal y prospectivo en 50 pacientes que fueron atendidos en el Servicio de Oculoplastia del Instituto Cubano de Oftalmología Ramón Pando Ferrer, con el diagnóstico de Dermatochalasis y/o hernia del tejido adiposo orbitario, de enero a junio del 2006. Se conformaron dos grupos de 25 pacientes seleccionados de forma aleatoria, uno para ser intervenido con láser y otro por la técnica convencional. Resultados: el mayor número de pacientes tratados quirúrgicamente por Dermatochalasis correspondió al grupo de edades entre 50 a 60 años, predominó la cirugía convencional. El 64,0 por ciento representaba al sexo femenino, se le aplicó dentro de este grupo la técnica convencional a un 68,0 por ciento. El 68,0 por ciento correspondió a pacientes de piel blanca, con un uso de 76 por ciento de láser de CO2. El 58,0 por ciento de estos pacientes se le realizó la técnica quirúrgica en un tiempo comprendido entre 30 y 45 minutos. Las complicaciones fueron hiperpigmentación al aplicar el láser de CO2 y la hipocorrección al utilizar la técnica convencional. Conclusiones: ambas técnicas quirúrgicas muestran resultados satisfactorios para el paciente, por lo que se convierten en una solución al problema estético y funcional del mismo, pero con el uso del láser de CO2 se redujo las complicaciones y el tiempo quirúrgico, siendo así la alternativa preferida por médicos y pacientes

Objective: to present the results of blepharoplasty with the conventional technique and with CO2 laser. Method: prospective, longitudinal and descriptive study of 50 patients with diagnosis of dermatochalasis and/or orbital fatty tissue hernia, who were assisted at the Oculoplasty service of Ramon Pando Ferrer Cuban Institute of Ophthalmology from January to June 2006. Two groups of 25 randomly selected patients were created; one to be operated on with laser and the other with the conventional procedure.Results: the highest number of patients surgically treated from dermatochalasis lied in 50-60 y age group and the conventional surgery was predominant. Females accounted for 64 percentv and in this group, the conventional technique was performed in 68 percent of patients. Sixty eight percent of patients were Caucasians, with use of CO2 laser amounted to 76 percent. The surgical time for 58 percent of these patients who underwent the surgical technique ranged 30 to 45 minutes. The complications were hyperpigmentation when using laser and hypocorrection when using the conventional technique. Conclusions: both surgical techniques show satisfactory results for the patients, so they become solutions to their esthetic and functional problems; however, CO2 laser reduced complications and the surgical times, so it is the alternative of choice for physicians and patients alike

Primary high-grade neuroendocrine carcinoma of the heart.

We report the successful resection of a solitary, apparently primary, high-grade neuroendocrine carcinoma of the heart, in a 70-year-old man who had presented with progressive dyspnea. The tumor occupied the right atrium and almost completely obstructed the superior and inferior venae cavae; it also involved the aortic root and the interatrial septum. To postpone the patient's impending cardiac failure, we resected the gross tumor except in the region of the aortic root and the trigone, which we debulked. We completely reconstructed the right atrium with pericardium and the interatrial septum with a pericardial patch. The patient recovered uneventfully; 18 months postoperatively, he had experienced only local recurrence in the tumor bed. This case shows that the palliative resection of large neuroendocrine tumors of the heart can yield good outcomes and prolong patient survival. To our knowledge, ours is the only report of a high-grade neuroendocrine cardiac tumor of apparently primary origin to have been resected with good palliative results.

Tricuspid valve replacement on a beating heart via a right minithoracotomy.

Right minithoracotomy provides an excellent exposure to the right atrium and the tricuspid valve. It is feasible and safe to perform a tricuspid valve replacement on a beating heart without cross-clamping the aorta via right minithoracotomy. The use of beating heart minimally invasive approach can decrease the morbidity and mortality of the procedure and still provide great exposure to the valve allowing either repair or replacement. The technical aspects of the procedure are described in a patient with carcinoid tricuspid valve disease.

Update on blunt thoracic aortic injury: fifteen-year single-institution experience.

OBJECTIVES: Despite improvements in the management of blunt thoracic aortic injury, mortality remains high. We report our experience with blunt thoracic aortic injury at a level 1 trauma center over the past 15 years. METHODS: Between January 1, 1997, and January 1, 2012, data on 338 patients who presented with suspected blunt thoracic aortic injury were entered into the University of Texas Medical School at Houston Trauma Center Registry. A total of 175 patients (52%) underwent thoracic aortic repair; 29 (17%) had open repair with aortic crossclamping, 77 (44%) had open repair with distal aortic perfusion, and 69 (39%) had thoracic endovascular aortic repair. Outcomes were determined, including early mortality, morbidity, length of stay, and late survival. Multiple logistic regression analysis was used to compute adjusted estimates for the effects of the operative technique. RESULTS: The early mortality for all patients with blunt thoracic aortic injury was 41% (139/338). Early mortality was 17% (27/175) for operative aortic interventions, 4% (3/69) for thoracic endovascular aortic repairs, 31% (11/29) for open repairs with aortic crossclamping, and 14% (11/77) for open repairs with distal aortic perfusion. Survival for thoracic endovascular aortic repair at 1 year and 5 years was 92% and 87%, respectively. Survival for open repair at 1, 5, 10, and 15 years was 76%, 75%, 72%, and 68%, respectively. CONCLUSIONS: Blunt thoracic aortic injury remains associated with significant early mortality. Delayed selective management, when applied with open repair with distal aortic perfusion and the use of thoracic endovascular aortic repair, has been associated with improved early outcomes. The long-term durability of thoracic endovascular aortic repair is unknown, necessitating close radiographic follow-up.

A transcriptomic analysis of Echinococcus granulosus larval stages: implications for parasite biology and host adaptation.

BACKGROUND: The cestode Echinococcus granulosus--the agent of cystic echinococcosis, a zoonosis affecting humans and domestic animals worldwide--is an excellent model for the study of host-parasite cross-talk that interfaces with two mammalian hosts. To develop the molecular analysis of these interactions, we carried out an EST survey of E. granulosus larval stages. We report the salient features of this study with a focus on genes reflecting physiological adaptations of different parasite stages. METHODOLOGY/PRINCIPAL FINDINGS: We generated ~10,000 ESTs from two sets of full-length enriched libraries (derived from oligo-capped and trans-spliced cDNAs) prepared with three parasite materials: hydatid cyst wall, larval worms (protoscoleces), and pepsin/H(+)-activated protoscoleces. The ESTs were clustered into 2700 distinct gene products. In the context of the biology of E. granulosus, our analyses reveal: (i) a diverse group of abundant long non-protein coding transcripts showing homology to a middle repetitive element (EgBRep) that could either be active molecular species or represent precursors of small RNAs (like piRNAs); (ii) an up-regulation of fermentative pathways in the tissue of the cyst wall; (iii) highly expressed thiol- and selenol-dependent antioxidant enzyme targets of thioredoxin glutathione reductase, the functional hub of redox metabolism in parasitic flatworms; (iv) candidate apomucins for the external layer of the tissue-dwelling hydatid cyst, a mucin-rich structure that is critical for survival in the intermediate host; (v) a set of tetraspanins, a protein family that appears to have expanded in the cestode lineage; and (vi) a set of platyhelminth-specific gene products that may offer targets for novel pan-platyhelminth drug development. CONCLUSIONS/SIGNIFICANCE: This survey has greatly increased the quality and the quantity of the molecular information on E. granulosus and constitutes a valuable resource for gene prediction on the parasite genome and for further genomic and proteomic analyses focused on cestodes and platyhelminths.

Characterisation of the native lipid moiety of Echinococcus granulosus antigen B.

Antigen B (EgAgB) is the most abundant and immunogenic antigen produced by the larval stage (metacestode) of Echinococcus granulosus. It is a lipoprotein, the structure and function of which have not been completely elucidated. EgAgB apolipoprotein components have been well characterised; they share homology with a group of hydrophobic ligand binding proteins (HLBPs) present exclusively in cestode organisms, and consist of different isoforms of 8-kDa proteins encoded by a polymorphic multigene family comprising five subfamilies (EgAgB1 to EgAgB5). In vitro studies have shown that EgAgB apolipoproteins are capable of binding fatty acids. However, the identity of the native lipid components of EgAgB remains unknown. The present work was aimed at characterising the lipid ligands bound to EgAgB in vivo. EgAgB was purified to homogeneity from hydatid cyst fluid and its lipid fraction was extracted using chloroform∶methanol mixtures. This fraction constituted approximately 40-50% of EgAgB total mass. High-performance thin layer chromatography revealed that the native lipid moiety of EgAgB consists of a variety of neutral (mainly triacylglycerides, sterols and sterol esters) and polar (mainly phosphatidylcholine) lipids. Gas-liquid chromatography analysis showed that 16∶0, 18∶0 and 18∶1(n-9) are the most abundant fatty acids in EgAgB. Furthermore, size exclusion chromatography coupled to light scattering demonstrated that EgAgB comprises a population of particles heterogeneous in size, with an average molecular mass of 229 kDa. Our results provide the first direct evidence of the nature of the hydrophobic ligands bound to EgAgB in vivo and indicate that the structure and composition of EgAgB lipoprotein particles are more complex than previously thought, resembling high density plasma lipoproteins. Results are discussed considering what is known on lipid metabolism in cestodes, and taken into account the Echinococcus spp. genomic information regarding both lipid metabolism and the EgAgB gene family.