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Stenotrophomonas, achromobacter, and nonmelioid burkholderia species: antimicrobial resistance and therapeutic strategies.

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Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nonmelioid Burkholderia species, namely, Burkholderia cepacia complex, collectively are a group of troublesome nonfermenters. Although not inherently virulent organisms, these environmental Gram negatives can complicate treatment in those who are immunocompromised, critically ill in the intensive care unit and those patients with suppurative lung disease, such as cystic fibrosis.

Through a range of intrinsic antimicrobial resistance mechanisms, virulence factors, and the ability to survive in biofilms, these opportunistic pathogens are well suited to persist, both in the environment and the host. Treatment recommendations are hindered by the difficulties in laboratory identification, the lack of reproducibility of antimicrobial susceptibility testing, the lack of clinical breakpoints, and the absence of clinical outcome data. Despite trimethoprim-sulfamethoxazole often being the mainstay of treatment, resistance is widely encountered, and alternative regimens, including combination therapy, are often used.

This review will highlight the important aspects and unique challenges that these three nonfermenters pose, and, in the absence of clinical outcome data, our therapeutic recommendations will be based on reported antimicrobial susceptibility and pharmacokinetic/pharmacodynamic profiles.

Vitamin D supplementation in children with asthma: a systematic review and meta-analysis.

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Epidemiologic studies suggest an association between vitamin D deficiency and atopic diseases, including asthma. The objective of this study was to systematically review the benefits and harms of vitamin D supplementation in children with asthma.

Methods : We used standard Cochrane systematic review methodology. The search strategy included an electronic search in February 2013 of MEDLINE and EMBASE. Two reviewers completed in duplicate and independently study selection, data abstraction, and assessment of risk of bias. We pooled the results of trials using a random-effects model. We assessed the quality of evidence by outcome using the GRADE methodology.

Results : Four trials with a total of 149 children met eligibility criteria. The trials had major methodological limitations. Given the four studies reporting on asthma symptoms used different instruments to measure that outcome, we opted not to conduct a meta-analysis. Three of those studies reported improvement in asthma symptoms in the vitamin D supplemented group study, while the fourth reported no effect (very low quality evidence). For the lung function outcome, a meta-analysis of two trials assessing post treatment FEV-1 found a mean difference of 0.54 liters per second (95% CI -5.28; 4.19; low quality evidence). For the vitamin D level outcome, a meta-analysis of three trials found a mean difference of 6.56 ng/ml (95% CI -0.64; 13.77; very low quality evidence).

Conclusions : The available very low to low quality evidence does not confirm or rule out beneficial effects of vitamin D supplementation in children with asthma. Large-scale, well-designed and executed randomized controlled trials are needed to better understand the effectiveness and safety of vitamin D in children with asthma.

Dietary agents for prevention and treatment of lung cancer.

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Lung cancer is a prominent cause of cancer-associated mortality worldwide. The main reason for high mortality due to lung cancer is attributable to the fact that the diagnosis is generally made when it has spread beyond a curable stage and cannot be treated surgically or with radiation therapy.

Therefore, new approaches like dietary modifications could be extremely useful in reducing lung cancer incidences. Several fruits and vegetables offer a variety of bioactive compounds to afford protection against several diseases, including lung cancer. A number of research studies involving dietary agents provide strong evidence for their role in the prevention and treatment of lung cancer, and have identified their molecular mechanisms of action and potential targets.

In this review article, we summarize data from in-vitro and in-vivo studies and where available, in clinical trials, on the effects of some of the most promising dietary agents against lung cancer.

Treatment of pulmonary arterial hypertension in children.

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Pulmonary arterial hypertension (PAH) is an important cause of morbidity and mortality in children. Improved understanding of the pathophysiological mechanisms of the underlying diseases has resulted in the development of effective, but not yet curative, therapies.

Currently, drugs from three main pharmacological groups targeting specific aberrant pathways (endothelin, nitric oxide, and prostacyclin) and four routes of administration (inhaled, intravenous, oral, and subcutaneous) have been approved for adult patients with PAH. However, only a minority of these drugs has been officially approved for children, mainly because randomized controlled studies are limited by the small number of paediatric patients with PAH worldwide. In children with progressive, severe PAH and an inadequate response to drug therapy, advances in interventional and surgical approaches have provided promising new strategies to avoid right ventricular deterioration. These techniques can delay or even avoid the need for lung transplantation.

In this Review, we present an update on developments in drug therapy for patients with PAH and highlight the current status of these treatments in children. We also describe the new surgical, interventional, and hybrid procedures, as well as their practical application in children with severe PAH.

Free radicals: properties, sources, targets, and their implication in various diseases.

Free radicals and other oxidants have gained importance in the field of biology due to their central role in various physiological conditions as well as their implication in a diverse range of diseases.

The free radicals, both the reactive oxygen species (ROS) and reactive nitrogen species (RNS), are derived from both endogenous sources (mitochondria, peroxisomes, endoplasmic reticulum, phagocytic cells etc.) and exogenous sources (pollution, alcohol, tobacco smoke, heavy metals, transition metals, industrial solvents, pesticides, certain drugs like halothane, paracetamol, and radiation). Free radicals can adversely affect various important classes of biological molecules such as nucleic acids, lipids, and proteins, thereby altering the normal redox status leading to increased oxidative stress. The free radicals induced oxidative stress has been reported to be involved in several diseased conditions such as diabetes mellitus, neurodegenerative disorders (Parkinson's disease-PD, Alzheimer's disease-AD and Multiple sclerosis-MS), cardiovascular diseases (atherosclerosis and hypertension), respiratory diseases (asthma), cataract development, rheumatoid arthritis and in various cancers (colorectal, prostate, breast, lung, bladder cancers).

This review deals with chemistry, formation and sources, and molecular targets of free radicals and it provides a brief overview on the pathogenesis of various diseased conditions caused by ROS/RNS.

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