Remisión a largo plazo de la hipertensión portopulmonar mediante trasplante hepático en paciente con cirrosis asociada a hepatitis autoinmune / Long term remission of portopulmonary hypertension with liver transplantation in a patient with cirrhosis associated to autoimmune hepatitis

La hipertensión portopulmonar (HTPP) es una complicación infrecuente de la hipertensión portal, que sigue un curso progresivo con un pronóstico sombrío. Los reportes en pacientes pediátricos son escasos y con períodos de seguimiento cortos. Se describe una paciente con cirrosis descompensada que desarrolló HTPP resuelta mediante trasplante hepático, que permanece asintomática tras diez años de seguimiento.

Portopulmonary hypertension is an uncommon complication of portal hypertension, running a progressive course with a negative prognosis. Reports in pediatric patients are scarce with short follow up. We describe the case of decompensated cirrhosis who developed PoPH and resolved with liver transplantation, remaining asymptomatic after ten years of follow up.

Long term remission of portopulmonary hypertension with liver transplantation in a patient with cirrhosis associated to autoimmune hepatitis. / Remisión a largo plazo de la hipertensión portopulmonar mediante trasplante hepático en paciente con cirrosis asociada a hepatitis autoinmune.

Portopulmonary hypertension is an uncommon complication of portal hypertension, running a progressive course with a negative prognosis. Reports in pediatric patients are scarce with short follow up. We describe the case of decompensated cirrhosis who developed PoPH and resolved with liver transplantation, remaining asymptomatic after ten years of follow up.

La hipertensión portopulmonar (HTPP) es una complicación infrecuente de la hipertensión portal, que sigue un curso progresivo con un pronóstico sombrío. Los reportes en pacientes pediátricos son escasos y con períodos de seguimiento cortos. Se describe una paciente con cirrosis descompensada que desarrolló HTPP resuelta mediante trasplante hepático, que permanece asintomática tras diez años de seguimiento.

Ion Binding Properties of a Naturally Occurring Metalloantibody.

LT1009 is a humanized version of murine LT1002 IgG1 that employs two bridging Ca2+ ions to bind its antigen, the biologically active lipid sphingosine-1-phosphate (S1P). We crystallized and determined the X-ray crystal structure of the LT1009 Fab fragment in 10 mM CaCl2 and found that it binds two Ca2+ in a manner similar to its antigen-bound state. Flame atomic absorption spectroscopy (FAAS) confirmed that murine LT1002 also binds Ca2+ in solution and inductively-coupled plasma-mass spectrometry (ICP-MS) revealed that, although Ca2+ is preferred, LT1002 can bind Mg2+ and, to much lesser extent, Ba2+. Isothermal titration calorimetry (ITC) indicated that LT1002 binds two Ca2+ ions endothermically with a measured dissociation constant (KD) of 171 µM. Protein and genome sequence analyses suggested that LT1002 is representative of a small class of confirmed and potential metalloantibodies and that Ca2+ binding is likely encoded for in germline variable chain genes. To test this hypothesis, we engineered, expressed, and purified a Fab fragment consisting of naïve murine germline-encoded light and heavy chain genes from which LT1002 is derived and observed that it binds Ca2+ in solution. We propose that LT1002 is representative of a class of naturally occurring metalloantibodies that are evolutionarily conserved across diverse mammalian genomes.

Attenuation of a select agent-excluded Burkholderia pseudomallei capsule mutant in hamsters.

Burkholderia pseudomallei is a Tier 1 select agent and potential bioweapon. Given it is potential to cause a lethal respiratory disease, research with fully virulent B. pseudomallei is conducted in Biosafety Level 3 (BSL-3) laboratory spaces. The logistical, financial, and administrative burden of Tier 1 select agent BSL-3 research has created an interest in mitigating such burdens through the use of either attenuated B. pseudomallei strains at BSL-2, or research with surrogate species, such as Burkholderia thailandensis. Previously, attenuated B. pseudomallei auxotroph mutants (asd and purM) have been approved for exclusion from select agent requirements, allowing for in vitro studies to be conducted at BSL-2. Acapsular B. pseudomallei mutants are known to be strongly attenuated in a variety of animal models, and yet acapsular B. pseudomallei mutants do not require nutritional supplementation, and can be studied within cultured macrophages, performing phenotypically similarly to parent strains. We demonstrate that the loss of a 30.8 kb region of the wcb capsule operon allows for a dramatic >4.46 log attenuation in a hamster intraperitoneal infection model, and report that this strain, JW270, has met criteria for exclusion from select agent requirements.

Respiratory Nursing Diagnoses: Presenting Evidence for Identification of the Defining Characteristics in Neonatal and Pediatric Populations.

PURPOSE: To identify and summarize clinical data supporting selection of nursing diagnoses related to the respiratory system for pediatric and neonatal populations. METHOD: A literature review conducted in indexed publications was used. FINDINGS: The final sample consisted of 13 studies conducted in children with cardiac disease, respiratory infection, and asthma with nursing diagnoses such as ineffective breathing pattern, impaired gas exchange, and ineffective airway clearance. CONCLUSION: The higher frequency defining characteristics were dyspnea, abnormal breathing pattern, use of accessory muscle to breathe, change in frequency and respiratory rate, decreased SaO2 , and agitation. IMPLICATION FOR NURSING KNOWLEDGE: This literature review may provide a basis for consideration of important diagnostic criteria in the pediatric population; however, clinical validation in different stages of development is critical for ensuring diagnostic accuracy.

Comprehensive identification of virulence factors required for respiratory melioidosis using Tn-seq mutagenesis.

Respiratory melioidosis is a disease presentation of the biodefense pathogen, Burkholderia pseudomallei, which is frequently associated with a lethal septicemic spread of the bacteria. We have recently developed an improved respiratory melioidosis model to study the pathogenesis of Burkholderia pseudomallei in the lung (intubation-mediated intratracheal [IMIT] inoculation), which more closely models descriptions of human melioidosis, including prominent septicemic spread from the lung and reduced involvement of the upper respiratory tract. We previously demonstrated that the Type 3 Secretion System cluster 3 (T3SS3) is a critical virulence determinant for B. pseudomallei when delivered directly into the lung. We decided to comprehensively identify all virulence determinants required for respiratory melioidosis using the Tn-seq phenotypic screen, as well as to investigate which virulence determinants are required for dissemination to the liver and spleen. While previous studies have used Tn-seq to identify essential genes for in vitro cultured B. pseudomallei, this represents the first study to use Tn-seq to identify genes required for in vivo fitness. Consistent with our previous findings, we identified T3SS3 as the largest genetic cluster required for fitness in the lung. Furthermore, we identified capsular polysaccharide and Type 6 Secretion System cluster 5 (T6SS5) as the two additional major genetic clusters facilitating respiratory melioidosis. Importantly, Tn-seq did not identify additional, novel large genetic systems supporting respiratory melioidosis, although these studies identified additional small gene clusters that may also play crucial roles in lung fitness. Interestingly, other previously identified virulence determinants do not appear to be required for lung fitness, such as lipopolysaccharide. The role of T3SS3, capsule, and T6SS5 in lung fitness was validated by competition studies, but only T3SS3 was found to be important for respiratory melioidosis when delivered as a single strain challenge, suggesting that competition studies may provide a higher resolution analysis of fitness factors in the lung. The use of Tn-seq phenotypic screening also provided key insights into the selective pressure encountered in the liver.

Type 3 secretion system cluster 3 is a critical virulence determinant for lung-specific melioidosis.

Burkholderia pseudomallei, the bacterial agent of melioidosis, causes disease through inhalation of infectious particles, and is classified as a Tier 1 Select Agent. Optical diagnostic imaging has demonstrated that murine respiratory disease models are subject to significant upper respiratory tract (URT) colonization. Because human melioidosis is not associated with URT colonization as a prominent presentation, we hypothesized that lung-specific delivery of B. pseudomallei may enhance our ability to study respiratory melioidosis in mice. We compared intranasal and intubation-mediated intratracheal (IMIT) instillation of bacteria and found that the absence of URT colonization correlates with an increased bacterial pneumonia and systemic disease progression. Comparison of the LD50 of luminescent B. pseudomallei strain, JW280, in intranasal and IMIT challenges of albino C57BL/6J mice identified a significant decrease in the LD50 using IMIT. We subsequently examined the LD50 of both capsular polysaccharide and Type 3 Secretion System cluster 3 (T3SS3) mutants by IMIT challenge of mice and found that the capsule mutant was attenuated 6.8 fold, while the T3SS3 mutant was attenuated 290 fold, demonstrating that T3SS3 is critical to respiratory melioidosis. Our previously reported intranasal challenge studies, which involve significant URT colonization, did not identify a dissemination defect for capsule mutants; however, we now report that capsule mutants exhibit significantly reduced dissemination from the lung following lung-specific instillation, suggesting that capsule mutants are competent to spread from the URT, but not the lung. We also report that a T3SS3 mutant is defective for dissemination following lung-specific delivery, and also exhibits in vivo growth defects in the lung. These findings highlight the T3SS3 as a critical virulence system for respiratory melioidosis, not only in the lung, but also for subsequent spread beyond the lung using a model system uniquely capable to characterize the fate of lung-delivered pathogen.

Intubation-mediated intratracheal (IMIT) instillation: a noninvasive, lung-specific delivery system.

Respiratory disease studies typically involve the use of murine models as surrogate systems. However, there are significant physiologic differences between the murine and human respiratory systems, especially in their upper respiratory tracts (URT). In some models, these differences in the murine nasal cavity can have a significant impact on disease progression and presentation in the lower respiratory tract (LRT) when using intranasal instillation techniques, potentially limiting the usefulness of the mouse model to study these diseases. For these reasons, it would be advantageous to develop a technique to instill bacteria directly into the mouse lungs in order to study LRT disease in the absence of involvement of the URT. We have termed this lung specific delivery technique intubation-mediated intratracheal (IMIT) instillation. This noninvasive technique minimizes the potential for instillation into the bloodstream, which can occur during more invasive traditional surgical intratracheal infection approaches, and limits the possibility of incidental digestive tract delivery. IMIT is a two-step process in which mice are first intubated, with an intermediate step to ensure correct catheter placement into the trachea, followed by insertion of a blunt needle into the catheter to mediate direct delivery of bacteria into the lung. This approach facilitates a >98% efficacy of delivery into the lungs with excellent distribution of reagent throughout the lung. Thus, IMIT represents a novel approach to study LRT disease and therapeutic delivery directly into the lung, improving upon the ability to use mice as surrogates to study human respiratory disease. Furthermore, the accuracy and reproducibility of this delivery system also makes it amenable to Good Laboratory Practice Standards (GLPS), as well as delivery of a wide range of reagents which require high efficiency delivery to the lung.

The influence of the initiation of an exercise programme on seroma formation and dehiscence following breast cancer surgery.

AIMS AND OBJECTIVES: To verify whether early (first post-operative day) or late initiation (after removal of the continuous suction drain) of a functional rehabilitation exercise programme influences the incidence of seroma formation and dehiscence for women after breast cancer surgery. BACKGROUND: Benefits of early implementation of an exercise programme initiated with women in the first days following breast cancer surgery are widely known. However, the safe initiation of the exercises is still a controversial issue and some authors correlate early initiation of the exercises with an increase in seroma formation. DESIGN: A prospective, randomised, controlled clinical trial. METHODS: Seventy-seven women were randomly assigned to initiate the programme on post-operative day 1 (early group = 40) or after removal of the drain (late group = 37) and were monitored until the 45th post-operative day. Patients in the early group were instructed to perform the exercises daily at home, beginning on post-operative day 1, while those of the late group began the exercises after the drain was removed. The assessment for seroma formation and dehiscence was performed on post-operative days 7 and 45. RESULTS: There was no statistically significant difference regard to seroma formation between early group and late group. Also there was no association between the presence of dehiscence and early exercises. CONCLUSION: The early initiation of the exercises for women, following breast cancer surgery, constitutes a safe practice for the rehabilitation. However, these findings need to be further explored and confirmed in a larger sample. RELEVANCE TO CLINICAL PRACTICE: Studies showing evidence that early functional rehabilitation process is a safe practice for women having surgery for breast cancer, as well as the present research, are of interest to health professionals who care for these patients and contribute to the wider global clinical community.

Carotenoids are more bioavailable from papaya than from tomato and carrot in humans: a randomised cross-over study.

Carrot, tomato and papaya represent important dietary sources of ß-carotene and lycopene. The main objective of the present study was to compare the bioavailability of carotenoids from these food sources in healthy human subjects. A total of sixteen participants were recruited for a randomised cross-over study. Test meals containing raw carrots, tomatoes and papayas were adjusted to deliver an equal amount of ß-carotene and lycopene. For the evaluation of bioavailability, TAG-rich lipoprotein (TRL) fractions containing newly absorbed carotenoids were analysed over 9·5 h after test meal consumption. The bioavailability of ß-carotene from papayas was approximately three times higher than that from carrots and tomatoes, whereas differences in the bioavailability of ß-carotene from carrots and tomatoes were insignificant. Retinyl esters appeared in the TRL fractions at a significantly higher concentration after the consumption of the papaya test meal. Similarly, lycopene was approximately 2·6 times more bioavailable from papayas than from tomatoes. Furthermore, the bioavailability of ß-cryptoxanthin from papayas was shown to be 2·9 and 2·3 times higher than that of the other papaya carotenoids ß-carotene and lycopene, respectively. The morphology of chromoplasts and the physical deposition form of carotenoids were hypothesised to play a major role in the differences observed in the bioavailability of carotenoids from the foods investigated. Particularly, the liquid-crystalline deposition of ß-carotene and the storage of lycopene in very small crystalloids in papayas were found to be associated with their high bioavailability. In conclusion, papaya was shown to provide highly bioavailable ß-carotene, ß-cryptoxanthin and lycopene and may represent a readily available dietary source of provitamin A for reducing the incidence of vitamin A deficiencies in many subtropical and tropical developing countries.

Properties of honey from ten species of Peruvian stingless bees.

Honey produced by ten stingless bee species (Melipona crinita, M. eburnea, M. grandis, M. illota, Nannotrigona melanocera, Partamona epiphytophila, Ptilotrigona lurida, Scaptotrigona polystica, Scaura latitarsis, and Tetragonisca angustula) from Peru has been characterized according to traditional physicochemical standards (color and moisture), biochemical components (flavonoids, polyphenols, nitrites, proteins), and bioactive properties (antibacterial activity, antioxidant capacity). Analytical data are also provided for a sample of Apis mellifera and an artificial honey control. For stingless bees, honey color varied between 26 and 150 mm Pfund. M. illota produced the lightest honey, while N. melanocera and T. angustula were the darkest. Moisture varied between 20.8 and 45.8 g water/100 g, confirming higher moisture for stingless bee honey than the A. mellifera honey standard of 20 g water/100 g. Flavonoids varied from 2.6 to 31.0 mg quercetin equivalents/100g, nitrites from 0.30 to 2.88 micromoles nitrites/100 g, polyphenols from 99.7 to 464.9 mg gallic acid equivalents/100g, proteins from 0.75 to 2.86 g/100 g, and the antioxidant capacity from 93.8 to 569.6 micromoles Trolox equivalents/100 g. The minimal inhibitory concentration (MIC) was slightly lower against Staphylococcus aureus (12.5 -50 g/100 mL) than Escherichia coli (50 g/100 mL).