A novel emergency department based prevention intervention program for people living with HIV: evaluation of early experiences

<p>Abstract</p> <p>Background</p> <p>HIV prevention is increasingly focused on people living with HIV (PLWH) and the role of healthcare settings in prevention. Emergency Departments (EDs) frequently care for PLWH, but do not typically endorse a prevention mission. We conducted a pilot exploratory evaluation of the first reported ED program to address the prevention needs of PLWH.</p> <p>Methods</p> <p>This retrospective observational cohort evaluation reviewed program records to describe the first six months of participants and programmatic operation. Trained counselors provided a risk assessment and counseling intervention combined with three linkage interventions: i) linkage to health care, ii) linkage to case management, and iii) linkage to partner counseling and referral.</p> <p>Results</p> <p>Of 81 self-identified PLWH who were approached, 55 initially agreed to participate. Of those completing risk assessment, 17/53 (32%, 95 CI 20% to 46%) reported unprotected anal/vaginal intercourse or needle sharing in the past six months with a partner presumed to be HIV negative. Counseling was provided to 52/53 (98%). For those requesting services, 11/15 (73%) were linked to healthcare, 4/23 (17%) were coordinated with case management, and 1/4 (25%) completed partner counseling and referral.</p> <p>Conclusion</p> <p>Given base resources of trained counselors, it was feasible to implement a program to address the prevention needs for persons living with HIV in an urban ED. ED patients with HIV often have unmet needs which might be addressed by improved linkage with existing community resources. Healthcare and prevention barriers for PLWH may be attenuated if EDs were to incorporate CDC recommended prevention measures for healthcare providers.</p

Pharmacological inhibition of leukotrienes in an animal model of bleomycin-induced acute lung injury

Leukotrienes are increased locally in idiopathic pulmonary fibrosis. Furthermore, a role for these arachidonic acid metabolites has been thoroughly characterized in the animal bleomycin model of lung fibrosis by using different gene knock-out settings. We investigated the efficacy of pharmacological inhibition of leukotrienes activity in the development of bleomycin-induced lung injury by comparing the responses in wild-type mice with mice treated with zileuton, a 5-lipoxygenase inhibitor and MK-571, a cys-leukotrienes receptor antagonist. Mice were subjected to intra-tracheal administration of bleomycin or saline and were assigned to receive either MK-571 at 1 mg/Kg or zileuton at 50 mg/Kg daily. One week after bleomycin administration, BAL cell counts, lung histology with van Gieson for collagen staining and immunohistochemical analysis for myeloperoxidase, IL-1 and TNF-α were performed. Following bleomycin administration both MK-571 and zileuton treated mice exhibited a reduced degree of lung damage and inflammation when compared to WT mice as shown by the reduction of:(i) loss of body weight, (ii) mortality rate, (iii) lung infiltration by neutrophils (myeloperoxidase activity, BAL total and differential cell counts), (iv) lung edema, (v) histological evidence of lung injury and collagen deposition, (vi) lung myeloperoxidase, IL-1 and TNF-α staining. This is the first study showing that the pharmacological inhibition of leukotrienes activity attenuates bleomycin-induced lung injury in mice. Given our results as well as those coming from genetic studies, it might be considered meaningful to trial this drug class in the treatment of pulmonary fibrosis, a disease that still represents a major challenge to medical treatment

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

How robust are the natural history parameters used in chlamydia transmission dynamic models? A systematic review

Transmission dynamic models linked to economic analyses often form part of the decision making process when introducing new chlamydia screening interventions. Outputs from these transmission dynamic models can vary depending on the values of the parameters used to describe the infection. Therefore these values can have an important influence on policy and resource allocation. The risk of progression from infection to pelvic inflammatory disease has been extensively studied but the parameters which govern the transmission dynamics are frequently neglected. We conducted a systematic review of transmission dynamic models linked to economic analyses of chlamydia screening interventions to critically assess the source and variability of the proportion of infections that are asymptomatic, the duration of infection and the transmission probability. We identified nine relevant studies in Pubmed, Embase and the Cochrane database. We found that there is a wide variation in their natural history parameters, including an absolute difference in the proportion of asymptomatic infections of 25% in women and 75% in men, a six-fold difference in the duration of asymptomatic infection and a four-fold difference in the per act transmission probability. We consider that much of this variation can be explained by a lack of consensus in the literature. We found that a significant proportion of parameter values were referenced back to the early chlamydia literature, before the introduction of nucleic acid modes of diagnosis and the widespread testing of asymptomatic individuals. In conclusion, authors should use high quality contemporary evidence to inform their parameter values, clearly document their assumptions and make appropriate use of sensitivity analysis. This will help to make models more transparent and increase their utility to policy makers

In Vivo Imaging of Transiently Transgenized Mice with a Bovine Interleukin 8 (CXCL8) Promoter/Luciferase Reporter Construct

One of the most remarkable properties of interleukin 8 (CXCL8/IL-8), a chemokine with known additional functions also in angiogenesis and tissue remodeling, is the variation of its expression levels. In healthy tissues, IL-8 is barely detectable, but it is rapidly induced by several folds in response to proinflammatory cytokines, bacterial or viral products, and cellular stress. Although mouse cells do not bear a clear homologous IL-8 gene, the murine transcriptional apparatus may well be capable of activating or repressing a heterologous IL-8 gene promoter driving a reporter gene. In order to induce a transient transgenic expression, mice were systemically injected with a bovine IL-8 promoter–luciferase construct. Subsequently mice were monitored for luciferase expression in the lung by in vivo bioluminescent image analysis over an extended period of time (up to 60 days). We demonstrate that the bovine IL-8 promoter–luciferase construct is transiently and robustly activated 3–5 hours after LPS and TNF-α instillation into the lung, peaking at 35 days after construct delivery. Bovine IL-8 promoter–luciferase activation correlates with white blood cell and neutrophil infiltration into the lung. This study demonstrates that a small experimental rodent model can be utilized for non-invasively monitoring, through a reporter gene system, the activation of an IL-8 promoter region derived from a larger size animal (bovine). This proof of principle study has the potential to be utilized also for studying primate IL-8 promoter regions

Effectiveness of hygienic-dietary recommendations as enhancers of antidepressant treatment in patients with Depression: Study protocol of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>In recent years some studies have been published supporting the efficacy of light exposure, physical activity, sleep control and a Mediterranean diet pattern on the improvement or prevention of Depression. However, to our knowledge, there have been no studies using all these measures together as an adjuvant antidepressant strategy.</p> <p>Methods</p> <p>Multicenter, randomized, controlled, two arm-parallel, clinical trial. Eighty depressed patients undergoing standard antidepressant treatment will be advised to follow four additional hygienic-dietary recommendations about exercise, diet, sunlight exposure and sleep. Outcome measures will be assessed before and after the 6 month intervention period.</p> <p>Discussion</p> <p>We expect the patients in the active recommendations group to experience a greater improvement in their depressive symptoms. If so, this would be a great support for doctors who might systematically recommend these simple and costless measures, especially in primary care.</p> <p>Trial Registration</p> <p>ISRCTN59506583</p

The Effects of Hydrogen Peroxide on the Circadian Rhythms of Microcystis aeruginosa

Background: The cyanobacterium Microcystis aeruginosa is one of the principal bloom-forming cyanobacteria present in a wide range of freshwater ecosystems. M. aeruginosa produces cyanotoxins, which can harm human and animal health. Many metabolic pathways in M. aeruginosa, including photosynthesis and microcystin synthesis, are controlled by its circadian rhythms. However, whether xenobiotics affect the cyanobacterial circadian system and change its growth, physiology and biochemistry is unknown. We used real-time PCR to study the effect of hydrogen peroxide (H2O2) on the expression of clock genes and some circadian genes in M. aeruginosa during the light/dark (LD) cycle. Results: The results revealed that H 2O 2 changes the expression patterns of clock genes (kaiA, kaiB, kaiC and sasA) and significantly decreases the transcript levels of kaiB, kaiC and sasA. H2O2 treatment also decreased the transcription of circadian genes, such as photosynthesis-related genes (psaB, psbD1 and rbcL) and microcystin-related genes (mcyA, mcyD and mcyH), and changed their circadian expression patterns. Moreover, the physiological functions of M. aeruginosa, including its growth and microcystin synthesis, were greatly influenced by H 2O 2 treatment during LD. These results indicate that changes in the cyanobacterial circadian system can affect its physiological and metabolic pathways. Conclusion: Our findings show that a xenobiotic can change the circadian expression patterns of its clock genes t

Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation

BACKGROUND: Theophylline has been used widely as a bronchodilator for the treatment of bronchial asthma and has been suggested to modulate immune response. While the importance of macrophages in asthma has been reappraised and emphasized, their significance has not been well investigated. We conducted a genome-wide profiling of the gene expressions of macrophages in response to theophylline. METHODS: Microarray technology was used to profile the gene expression patterns of macrophages modulated by theophylline. Northern blot and real-time quantitative RT-PCR were also used to validate the microarray data, while Western blot and ELISA were used to measure the levels of IL-13 and LTC4. RESULTS: We identified dozens of genes in macrophages that were dose-dependently down- or up-regulated by theophylline. These included genes related to inflammation, cytokines, signaling transduction, cell adhesion and motility, cell cycle regulators, and metabolism. We observed that IL-13, a central mediator of airway inflammation, was dramatically suppressed by theophylline. Real-time quantitative RT-PCR and ELISA analyses also confirmed these results, without respect to PMA-treated THP-1 cells or isolated human alveolar macrophages. Theophylline, rolipram, etazolate, db-cAMP and forskolin suppressed both IL-13 mRNA expression (~25%, 2.73%, 8.12%, 5.28%, and 18.41%, respectively) and protein secretion (<10% production) in macrophages. These agents also effectively suppressed LTC4 expression. CONCLUSION: Our results suggest that the suppression of IL-13 by theophylline may be through cAMP mediation and may decrease LTC4 production. This study supports the role of theophylline as a signal regulator of inflammation, and that down regulation of IL-13 by theophylline may have beneficial effects in inflammatory airway diseases