An ovine model of hyperdynamic endotoxemia and vital organ metabolism

BACKGROUND: Animal models of endotoxemia are frequently used to understand the pathophysiology of sepsis and test new therapies. However, important differences exist between commonly used experimental models of endotoxemia and clinical sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in contrast to clinical hyperdynamic shock. This difference may exaggerate the importance of hypoperfusion as a causative factor in organ dysfunction. This study sought to develop an ovine model of hyperdynamic endotoxemia and assess if there is evidence of impaired oxidative metabolism in the vital organs. METHODS: Eight sheep had microdialysis catheters implanted into the brain, heart, liver, kidney and arterial circulation. Shock was induced with a 4hr escalating dose infusion of endotoxin. After 3hrs vasopressor support was initiated with noradrenaline and vasopressin. Animals were monitored for 12hrs after endotoxemia. Blood samples were recovered for haemoglobin, white blood cell count, creatinine and proinflammatory cytokines (IL-1Beta, IL-6 & IL-8). RESULTS: The endotoxin infusion was successful in producing distributive shock with the mean arterial pressure decreasing from 84.5 ± 12.8 mmHg to 49 ± 8.03 mmHg (p < 0.001). Cardiac index remained within the normal range decreasing from 3.33 ± 0.56 l/min/m to 2.89l ± 0.36 l/min/m (p = 0.0845). Lactate/pyruvate ratios were not significantly abnormal in the heart, brain, kidney or arterial circulation. Liver microdialysis samples demonstrated persistently high lactate/pyruvate ratios (mean 37.9 ± 3.3). CONCLUSIONS: An escalating dose endotoxin infusion was successful in producing hyperdynamic shock. There was evidence of impaired oxidative metabolism in the liver suggesting impaired splanchnic perfusion. This may be a modifiable factor in the progression to multiple organ dysfunction and death

Factors associated with the desire for orthodontic treatment among Brazilian adolescents and their parents

<p>Abstract</p> <p>Background</p> <p>In the period of adolescence physical appearance takes on significant importance in the construction of personal identity, including one's relationship with one's own body. A variety of social, cultural, psychological and personal factors influences the self-perception of dental appearance and the decision to undergo orthodontic treatment. Adolescents who seek orthodontic treatment are concerned with improving their appearance and social acceptance. The aim of the present study was to determine factors associated to the desire for orthodontic treatment among Brazilian adolescents and their parents.</p> <p>Methods</p> <p>The sample consisted of 403 subjects aged 14 to 18 years, selected randomly from a population of 182,291 schoolchildren in the same age group. The outcome variable "desire for orthodontic treatment" was assessed through a questionnaire. Self-perception of dental aesthetics was assessed using the Oral Aesthetic Subjective Impact Scale (OASIS) and the Dental Aesthetic Index (DAI) was used for clinical assessment. Statistical analysis involved the chi-square test as well as both simple and multiple logistic regression analyses.</p> <p>Results</p> <p>The majority (78%) of the Brazilian adolescents desired orthodontic treatment and 69% of the parents reported that their children were not in orthodontic treatment due to the high costs involved. There was significant association (p ≤ 0.05) between the desire for orthodontic treatment and most types of malocclusion. However, there was no significant association between the desire for orthodontic treatment and the variables gender and age.</p> <p>Conclusions</p> <p>The following were considered factors associated to the desire for treatment: upper anterior crowding ≥ 2 mm and parents' perception of their child's need for treatment.</p

Facile Synthesis of Monodisperse CdS Nanocrystals via Microreaction

CdS-based nanocrystals (NCs) have attracted extensive interest due to their potential application as key luminescent materials for blue and white LEDs. In this research, the continuous synthesis of monodisperse CdS NCs was demonstrated utilizing a capillary microreactor. The enhanced heat and mass transfer in the microreactor was useful to reduce the reaction temperature and residence time to synthesize monodisperse CdS NCs. The superior stability of the microreactor and its continuous operation allowed the investigation of synthesis parameters with high efficiency. Reaction temperature was found to be a key parameter for balancing the reactivity of CdS precursors, while residence time was shown to be an important factor that governs the size and size distribution of the CdS NCs. Furthermore, variation of OA concentration was demonstrated to be a facile tuning mechanism for controlling the size of the CdS NCs. The variation of the volume percentage of OA from 10.5 to 51.2% and the variation of the residence time from 17 to 136 s facilitated the synthesis of monodisperse CdS NCs in the size range of 3.0–5.4 nm, and the NCs produced photoluminescent emissions in the range of 391–463 nm

The progestational and androgenic properties of medroxyprogesterone acetate: gene regulatory overlap with dihydrotestosterone in breast cancer cells

INTRODUCTION: Medroxyprogesterone acetate (MPA), the major progestin used for oral contraception and hormone replacement therapy, has been implicated in increased breast cancer risk. Is this risk due to its progestational or androgenic properties? To address this, we assessed the transcriptional effects of MPA as compared with those of progesterone and dihydrotestosterone (DHT) in human breast cancer cells. METHOD: A new progesterone receptor-negative, androgen receptor-positive human breast cancer cell line, designated Y-AR, was engineered and characterized. Transcription assays using a synthetic promoter/reporter construct, as well as endogenous gene expression profiling comparing progesterone, MPA and DHT, were performed in cells either lacking or containing progesterone receptor and/or androgen receptor. RESULTS: In progesterone receptor-positive cells, MPA was found to be an effective progestin through both progesterone receptor isoforms in transient transcription assays. Interestingly, DHT signaled through progesterone receptor type B. Expression profiling of endogenous progesterone receptor-regulated genes comparing progesterone and MPA suggested that although MPA may be a somewhat more potent progestin than progesterone, it is qualitatively similar to progesterone. To address effects of MPA through androgen receptor, expression profiling was performed comparing progesterone, MPA and DHT using Y-AR cells. These studies showed extensive gene regulatory overlap between DHT and MPA through androgen receptor and none with progesterone. Interestingly, there was no difference between pharmacological MPA and physiological MPA, suggesting that high-dose therapeutic MPA may be superfluous. CONCLUSION: Our comparison of the gene regulatory profiles of MPA and progesterone suggests that, for physiologic hormone replacement therapy, the actions of MPA do not mimic those of endogenous progesterone alone. Clinically, the complex pharmacology of MPA not only influences its side-effect profile; but it is also possible that the increased breast cancer risk and/or the therapeutic efficacy of MPA in cancer treatment is in part mediated by androgen receptor

Pharmacological Inhibition of Caspase and Calpain Proteases: A Novel Strategy to Enhance the Homing Responses of Cord Blood HSPCs during Expansion

Background: Expansion of hematopoietic stem/progenitor cells (HSPCs) is a well-known strategy employed to facilitate the transplantation outcome. We have previously shown that the prevention of apoptosis by the inhibition of cysteine proteases, caspase and calpain played an important role in the expansion and engraftment of cord blood (CB) derived HSPCs. We hypothesize that these protease inhibitors might have maneuvered the adhesive and migratory properties of the cells rendering them to be retained in the bone marrow for sustained engraftment. The current study was aimed to investigate the mechanism of the homing responses of CB cells during expansion. Methodology/Principal Findings: CB derived CD34 + cells were expanded using a combination of growth factors with and without Caspase inhibitor-zVADfmk or Calpain 1 inhibitor- zLLYfmk. The cells were analyzed for the expression of homingrelated molecules. In vitro adhesive/migratory interactions and actin polymerization dynamics of HSPCs were assessed. In vivo homing assays were carried out in NOD/SCID mice to corroborate these observations. We observed that the presence of zVADfmk or zLLYfmk (inhibitors) caused the functional up regulation of CXCR4, integrins, and adhesion molecules, reflecting in a higher migration and adhesive interactions in vitro. The enhanced actin polymerization and the RhoGTPase protein expression complemented these observations. Furthermore, in vivo experiments showed a significantly enhanced homing to the bone marrow of NOD/SCID mice

Revisión de la literatura integradora acerca de intervenciones de la enfermería volcadas hacia el incremento del autocuidado entre pacientes con insuficiencia cardiaca

Objective: to analyze and summarize knowledge concerning critical components of interventions that have been proposed and implemented by nurses with the aim of optimizing self-care by heart failure patients.Methods: PubMed and CINAHL were the electronic databases used to search full peer-reviewed papers, presenting descriptions of nursing interventions directed to patients or to patients and their families and designed to optimize self-care. Forty-two studies were included in the final sample (n=4,799 patients).Results: this review pointed to a variety and complexity of nursing interventions. As self-care encompasses several behaviors, interventions targeted an average of 3.6 behaviors. Educational/counselling activities were combined or not with cognitive behavioral strategies, but only about half of the studies used a theoretical background to guide interventions. Clinical assessment and management were frequently associated with self-care interventions, which varied in number of sessions (1 to 30); length of follow-up (2 weeks to 12 months) and endpoints.Conclusions: these findings may be useful to inform nurses about further research in self-care interventions in order to propose the comparison of different modalities of intervention, the use of theoretical background and the establishment of endpoints to evaluate their effectiveness.Objetivo:analisar e sintetizar o conchecimento relacionado aos componentes críticos das intervençoes que têm, sido propostas e implementadas por enfermeiros(as) com objetivo de optimizar o auto-cuidado de pacientes portadores de insuficiência cardíaca.Método:PubMed e CINAHL foram as bases de dados electrônicas utilizadas para investigar artigos revisados por pares (peer review), apresentando as descrições das intervenções dirigidas ao paciente ou ao paciente e sua familia, visando melhorar o auto-cuidado. Foram incluídos 42 estudos na amostra final (n=4799 pacientes).Resultados:esta revisão apontou variedade e complexidade das intervenções de enfermagem. Como o auto-cuidado envolve diferentes comportamentos, as intervenções visaram em média 3,6 comportamentos. As Atividades de educação e aconselhamento foram combinadas ou não com estratégias cognitivo-comportamentais, mas somente a metade dos estudos utilizaram suporte teórico para guiar as intervenções. A avaliação e o manejo clínico foram frequentemente associados às intervenções de auto-cuidado, as quais variam em número de sessões (1 a 30), duração do seguimento (2 semanas a 12 meses) e desfechos.Conclusão:estes resultados podem ser úteis para guiar os enfermeiros no que se refere à futuros estudos sobre intervenções de auto-cuidado, de maneira a propor a comparação de diferentes modalidades de intervenção, uso de suporte teórico e estabelecimento de desfechos para melhor avaliar sua eficácia.Objetivo:analizar y sintetizar el conocimiento relacionado a componentes críticos de intervenciones que han sido propuestas e implementadas por enfermeros(as) con el objetivo de optimizar el autocuidado entre pacientes con insuficiencia cardiaca.Método:PUBMED y CINAHL han sido las bases de datos electrónicas usadas para investigar artículos revisados por pares (peer review), presentando descripciones de intervenciones destinadas a perfeccionar el autocuidado dirigido al paciente o al paciente y a su familia. Se incluyeron 42 estudios en la muestra final (n=4799 pacientes).Resultados:esta revisión apuntó a una variedad y complejidad de intervenciones de enfermería. Como el autocuidado abarca varios comportamientos, las intervenciones tuvieron como blanco, en media, 3,6 comportamientos. Actividades de educación/consejería fueron combinadas o no con estrategias cognitivo-comportamentales, pero tan solo cerca de la mitad de los estudios tenían aporte teórico para guiar intervenciones. La gestión y la evaluación clínica fueron frecuentemente asociadas a intervenciones de autocuidado, las cuales oscilaron en número de sesiones (1 a 30), duración del seguimiento (2 semanas a 12 meses) y objetivos.Conclusiones:estos resultados pueden ser útiles para informar a las enfermeras acerca de nuevas investigaciones en intervenciones de autocuidado, de modo a proponer la comparación de distintas modalidades de intervención, el uso de un aporte teórico y el establecimiento de objetivos para evaluar su eficacia

Chemical Modification of Graphene Oxide by Nitrogenation: An X-ray Absorption and EmissionSpectroscopy Study

Nitrogen-doped graphene oxides (GO:Nx) were synthesized by a partial reduction of graphene oxide (GO) using urea [CO(NH2)2]. Their electronic/bonding structures were investigated using X-ray absorption near-edge structure (XANES), valence-band photoemission spectroscopy (VB-PES), X-ray emission spectroscopy (XES) and resonant inelastic X-ray scattering (RIXS). During GO:Nx synthesis, different nitrogen-bonding species, such as pyrrolic/graphitic-nitrogen, were formed by replacing of oxygen-containing functional groups. At lower N-content (2.7 at%), pyrrolic-N, owing to surface and subsurface diffusion of C, N and NH is deduced from various X-ray spectroscopies. In contrast, at higher N-content (5.0 at%) graphitic nitrogen was formed in which each N-atom trigonally bonds to three distinct sp2-hybridized carbons with substitution of the N-atoms for C atoms in the graphite layer. Upon nitrogen substitution, the total density of state close to Fermi level is increased to raise the valence-band maximum, as revealed by VB-PES spectra, indicating an electron donation from nitrogen, molecular bonding C/N/O coordination or/and lattice structure reorganization in GO:Nx. The well-ordered chemical environments induced by nitrogen dopant are revealed by XANES and RIXS measurements

Group B <em>Streptococcus </em>engages an inhibitory siglec through sialic acid mimicry to blunt innate immune and inflammatory responses <em>in vivo</em>

Group B Streptococcus (GBS) is a common agent of bacterial sepsis and meningitis in newborns. The GBS surface capsule contains sialic acids (Sia) that engage Sia-binding immunoglobulin-like lectins (Siglecs) on leukocytes. Here we use mice lacking Siglec-E, an inhibitory Siglec of myelomonocytic cells, to study the significance of GBS Siglec engagement during in vivo infection. We found GBS bound to Siglec-E in a Sia-specific fashion to blunt NF-κB and MAPK activation. As a consequence, Siglec-E-deficient macrophages had enhanced pro-inflammatory cytokine secretion, phagocytosis and bactericidal activity against the pathogen. Following pulmonary or low-dose intravenous GBS challenge, Siglec-E KO mice produced more pro-inflammatory cytokines and exhibited reduced GBS invasion of the central nervous system. In contrast, upon high dose lethal challenges, cytokine storm in Siglec-E KO mice was associated with accelerated mortality. We conclude that GBS Sia mimicry influences host innate immune and inflammatory responses in vivo through engagement of an inhibitory Siglec, with the ultimate outcome of the host response varying depending upon the site, stage and magnitude of infection

Intracellular lumen extension requires ERM-1-dependent apical membrane expansion and AQP-8-mediated flux

SUMMARY Many unicellular tubes such as capillaries form lumens intracellularly, a process that is not well understood. Here we show that the cortical membrane organizer ERM-1 is required to expand the intracellular apical/lumenal membrane and its actin undercoat during single-cell C.elegans excretory canal morphogenesis. We characterize AQP-8, identified in an ERM-1 overexpression (ERM-1[++]) suppressor screen, as a canalicular aquaporin that interacts with ERM-1 in lumen extension in a mercury-sensitive manner, implicating water-channel activity. AQP-8 is transiently recruited to the lumen by ERM-1, co-localizing in peri-lumenal cuffs interspaced along expanding canals. An ERM-1[++]-mediated increase in the number of lumen-associated canaliculi is reversed by AQP-8 depletion. We propose that the ERM-1-AQP-8 interaction propels lumen extension by translumenal flux, suggesting a direct morphogenetic effect of water-channel-regulated fluid pressure