In-Silico Identification, Characterization and Expression Analysis of Genes Involved in Resistant Starch Biosynthesis in Potato (Solanum tuberosum L.) Varieties.

Potato (Solanum tuberosum L.), an important horticultural crop is a member of the family Solanaceae and is mainly grown for consumption at global level. Starch, the principal component of tubers, is one of the significant elements for food and non-food-based applications. The genes associated with biosynthesis of starch have been investigated extensively over the last few decades. However, a complete regulation pathway of constituent of amylose and amylopectin are still not deeply explored. The current in-silico study of genes related to amylose and amylopectin synthesis and their genomic organization in potato is still lacking. In the current study, the nucleotide and amino acid arrangement in genome and twenty-two genes linked to starch biosynthesis pathway in potato were analysed. The genomic structure analysis was also performed to find out the structural pattern and phylogenetic relationship of genes. The genome mining and structure analysis identified ten specific motifs and phylogenetic analysis of starch biosynthesis genes divided them into three different clades on the basis of their functioning and phylogeny. Quantitative real-time PCR (qRT-PCR) of amylose biosynthesis pathway genes in three contrast genotypes revealed the down-gene expression that leads to identify potential cultivar for functional genomic approaches. These potential lines may help to achieve higher content of resistant starch.

In vitro induction and selection of mutants obtained through gamma irradiation with improved processing traits in potato (Solanum tuberosum L.).

PURPOSE: This manuscript aimed for the generation of γ-irradiation derived mutants of potato genotype PAU/RR-1501 possessing desirable processing traits. MATERIALS AND METHODS: Nodal cuttings from virus-free explants were established on basal MS medium and irradiated with different doses (0, 5, 10 and 20 Gy) of γ-irradiation. The 5 and 10 Gy treated plantlets were multiplied and used for micro-tuber induction. Harvested micro-tubers were planted in pots for the selection and evaluation of mutants in M1V2 generation. RESULTS: Four weeks post-treatment, plantlets (5 Gy) showed enhanced growth as compared to the control while 20 Gy treatment exhibited completely ceased shoot growth. The highest number and weight of mini-tubers per plant was recorded for 10 Gy followed by 5 Gy treatment as compared to control. The γ-irradiation treatments caused changes in the skin color and shape of M1V2 tubers. CONCLUSION: Under the 5 Gy treatment 49.9% of clones produced exhibited cream and 8.53% brown skin color. Nine putative mutants were identified in genotype PAU/RR-1501 exhibiting promising processing traits.

Breeding strategies for late blight resistance in potato crop: recent developments.

Late blight (LB) is a serious disease that affects potato crop and is caused by Phytophthora infestans. Fungicides are commonly used to manage this disease, but this practice has led to the development of resistant strains and it also poses serious environmental and health risks. Therefore, breeding for resistance development can be the most effective strategies to control late blight. Various Solanum species have been utilized as a source of resistance genes to combat late blight disease. Several potential resistance genes and quantitative resistance loci (QRLs) have been identified and mapped through the application of molecular techniques. Furthermore, molecular markers closely linked to resistance genes or QRLs have been utilized to hasten the breeding process. However, the use of single-gene resistance can lead to the breakdown of resistance within a short period. To address this, breeding programs are now being focused on development of durable and broad-spectrum resistant cultivars by combining multiple resistant genes and QRLs using advanced molecular breeding tools such as marker-assisted selection (MAS) and cis-genic approaches. In addition to the strategies mentioned earlier, somatic hybridization has been utilized for the development and characterization of interspecific somatic hybrids. To further broaden the scope of late blight resistance breeding, approaches such as genomic selection, RNAi silencing, and various genome editing techniques can be employed. This study provides an overview of recent advances in various breeding strategies and their applications in improving the late blight resistance breeding program.

Multi-Wall Carbon Nanotubes, Metal Oxide and Hydroxy-Apatite Nanoparticles Enhanced Plant Growth Promoting Capabilities of Root Endosymbionts of Cowpea (Vigna unguiculata (L.) Walp.).

The present study was aimed to evaluate the effect of three different nanomaterials (NMs) on the growth, physiology and protein profile of the endosymbiotic bacteria isolated from the root nodules of vegetable cowpea. The alterations in growth and viability of the bacterial cells, their indole-acetic acid (IAA) and siderophore production abilities, phosphate solubilization potential and total protein content were assessed. Further, the isolates were also analyzed for changes in their exopolysaccharide (EPS) production and secretion behavior with exposure to different concentrations of the NMs. The NM supplementation of the broth improved the growth, viable cell count, IAA content, siderophore production and potential to solubilize tri-calcium phosphate (TCP) as sole phosphorus (P)-source. The NMs also improved the total protein content of the bacterial cells indicating the improved physiology and biochemistry of the treated bacterial cells. The treated cells produced significantly high EPS compared to untreated control cultures. The present investigation revealed that the NMs improved plant growth abilities of cowpea root endosymbiotic bacteria, though the impact varied across various isolates as well as NM concentrations.

Chitosan-Urea Nanocomposite for Improved Fertilizer Applications: The Effect on the Soil Enzymatic Activities and Microflora Dynamics in N Cycle of Potatoes (Solanum tuberosum L.).

The impact of polymer-based slow-release urea formulations on soil microbial N dynamics in potatoes has been sparingly deciphered. The present study investigated the effect of a biodegradable nano-polymer urea formulation on soil enzymatic activities and microflora involved in the N cycling of potato (Solanum tuberosum L.). The nano-chitosan-urea composite (NCUC) treatment significantly increased the soil dehydrogenase activity, organic carbon content and available potassium compared to the conventional urea (CU) treatment. The soil ammonical nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) contents and urease activity were significantly decreased in the NCUC-amended soil. The slow urea hydrolysis rate led to low concentrations of NH4+-N and NO3--N in the tested potato soil. Furthermore, these results corroborate the low count of ammonia oxidizer and nitrate reducer populations. Quantitative PCR (q-PCR) studies revealed that the relative abundance of eubacterial (AOB) and archaeal ammonia-oxidizing (AOA) populations was reduced in the NCUC-treated soil compared to CU. The abundance of AOA was particularly lower than AOB, probably due to the more neutral and alkaline conditions of the tested soil. Our results suggest that the biodegradable polymer urea composite had a significant effect on the microbiota associated with soil N dynamics. Therefore, the developed NCUC could be used as a slow N-release fertilizer for enhanced growth and crop yields of potato.

Genetic diversity and interrelationship among Indian and exotic melons based on fruit morphology, quality components and microsatellite markers.

Seventy melon (Cucumis melo L.) accessions comprising of landraces, inbred lines, cultivars, wild relatives and exotic populations were characterized using fifteen fruit traits and 30 SSR markers. Overall, aim of this study was to investigate the genetic relatedness across origins, horticultural groups and accession categories. Significant differences were observed for days to first fruit maturity, fruit weight, fruits per vine, yield per plant, flesh thickness, fruit shape index, total soluble solids, ß-carotene, ascorbic acid and titrable acidity. Twenty-four polymorphic SSRs detected 67 distinct alleles with moderate polymorphic information content (0.43) and genetic diversity (0.44). Observed heterozygosity (0.53) was higher than expected heterozygosity (0.48) which can be attributed to out-cross nature of melons. Neighbor joining tree based on SSRs diverged 70 accessions into six clusters independent of geographic sites of collections. Momordica and inodorus accessions formed distinct clusters, with some exceptions. Intermixing of landraces, modern cultivars and exotic accessions belonging to different taxa and geographic regions indicated genetic resemblance with each other. Hybridization among exotic and indigenous genetic resources can be utilized for genetic enhancement and introgression of new traits in modern melon cultivars.

Bupropion for smoking cessation in patients hospitalized with acute myocardial infarction: a randomized, placebo-controlled trial.

OBJECTIVES: The purpose of this study was to examine smoking cessation rates among smokers with AMI to determine whether bupropion, started in-hospital, is safe and can improve cessation rates at 1 year. BACKGROUND: Bupropion doubles quit rates in otherwise healthy smokers and patients with stable cardiovascular disease. Although 2 previous trials examined the use of bupropion in patients hospitalized with acute cardiovascular disease, these studies have been inconclusive with respect to its safety and efficacy in patients with acute myocardial infarction (AMI). METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized trial in smokers hospitalized with AMI. Participants received bupropion or placebo for 9 weeks and were followed for 12 months. Both groups received low-intensity counseling. Point prevalence abstinence was assessed by 7-day recall and biochemical validation of expired carbon monoxide. RESULTS: A total of 392 patients were randomized (mean age 53.9 ± 10.3 years); 83.5% were male; 64.9% had ST-segment elevation myocardial infarction). Patients smoked a mean of 23.2 ± 10.6 cigarettes/day for a mean of 32.9 ± 12.4 years. At 12 months, point prevalence abstinence rates were 37.2% in the bupropion group and 32.0% in the placebo group (p = 0.33; % difference after adjusting for between center differences 3.9%). Continuous abstinence rates were 26.8% and 22.2%, respectively (p = 0.34). Major adverse cardiac event rates were similar (13.0% vs. 11.0%, respectively; p = 0.64). CONCLUSIONS: Two-thirds of patients return to smoking by 12 months after AMI. Bupropion is well tolerated and seems to be safe to use in the immediate post-AMI period. However, bupropion is not effective for smoking cessation in patients post-AMI.

The impact of repeated marathon running on cardiovascular function in the aging population.

BACKGROUND: Several studies have correlated elevations in cardiac biomarkers of injury post marathon with transient and reversible right ventricular (RV) systolic dysfunction as assessed by both transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR). Whether or not permanent myocardial injury occurs due to repeated marathon running in the aging population remains controversial. OBJECTIVES: To assess the extent and severity of cardiac dysfunction after the completion of full marathon running in individuals greater than 50 years of age using cardiac biomarkers, TTE, cardiac computed tomography (CCT), and CMR. METHODS: A total of 25 healthy volunteers (21 males, 55 ± 4 years old) from the 2010 and 2011 Manitoba Full Marathons (26.2 miles) were included in the study. Cardiac biomarkers and TTE were performed one week prior to the marathon, immediately after completing the race and at one-week follow-up. CMR was performed at baseline and within 24 hours of completion of the marathon, followed by CCT within 3 months of the marathon. RESULTS: All participants demonstrated an elevated cTnT post marathon. Right atrial and ventricular volumes increased, while RV systolic function decreased significantly immediately post marathon, returning to baseline values one week later. Of the entire study population, only two individuals demonstrated late gadolinium enhancement of the subendocardium in the anterior wall of the left ventricle, with evidence of stenosis of the left anterior descending artery on CCT. CONCLUSIONS: Marathon running in individuals over the age of 50 is associated with a transient, yet reversible increase in cardiac biomarkers and RV systolic dysfunction. The presence of myocardial fibrosis in older marathon athletes is infrequent, but when present, may be due to underlying occult coronary artery disease.

Obstructive sleep apnea: effects of continuous positive airway pressure on cardiac remodeling as assessed by cardiac biomarkers, echocardiography, and cardiac MRI.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular morbidity and mortality. Although previous echocardiographic studies have demonstrated short-term improvement in cardiovascular remodeling in patients with OSA receiving continuous positive airway pressure (CPAP) therapy, a long-term study incorporating cardiac biomarkers, echocardiography, and cardiac MRI (CMR) has not been performed to date. METHODS: A prospective study of 47 patients with OSA was performed between 2007 and 2010. Cardiac biomarkers, including C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and troponin T (TnT), were measured at baseline and serially over 1 year. All patients underwent baseline and serial transthoracic echocardiography (TTE) and CMR to assess cardiac remodeling. RESULTS: Following 12 months of CPAP therapy, levels of CRP, NT-proBNP, and TnT did not change significantly from normal baseline values. As early as 3 months after initiation of CPAP, TTE revealed an improvement in right ventricular end-diastolic diameter, left atrial volume index, right atrial volume index, and degree of pulmonary hypertension, which continued to improve over 1 year of follow-up. Finally, left ventricular mass, as determined by CMR, decreased from 159 ± 12 g/m(2) to 141 ± 8 g/m(2) as early as 6 months into CPAP therapy and continued to improve until completion of the study at 1 year. CONCLUSION: Both systolic and diastolic abnormalities in patients with OSA can be reversed as early as 3 months into CPAP therapy, with progressive improvement in cardiovascular remodeling over 1 year as assessed by both TTE and CMR.

The role of three-dimensional echocardiography in the assessment of right ventricular dysfunction after a half marathon: comparison with cardiac magnetic resonance imaging.

BACKGROUND: Although marathon running is associated with transient right ventricular (RV) systolic dysfunction as detected by two-dimensional transthoracic echocardiography, quantitative assessment of the right ventricle is difficult because of its complex geometry. Little is known about the use of real-time three-dimensional echocardiography (RT3DE) in the detection of cardiac dysfunction after a half marathon. The aim of this study was to assess the extent of RV dysfunction after the completion of a half marathon using cardiac biomarkers, RT3DE, and cardiac magnetic resonance imaging (CMR). METHODS: A prospective study was performed in 15 individuals in 2009 participating in the Manitoba Half Marathon. Cardiac biomarkers (myoglobin, creatine kinase-MB and cardiac troponin T) were assessed and RT3DE and CMR were performed 1 week before, immediately after, and 1 week after the race. RESULTS: At baseline, cardiac biomarkers and ventricular function were within normal limits. Immediately following the half marathon, all patients demonstrated elevated cardiac troponin T levels, with a median value of 0.37 ng/mL. RV ejection fraction, as assessed by RT3DE, decreased from 59 ± 4% at baseline to 45 ± 5% immediately following the race (P < .05). On CMR, RV end-diastolic volume increased after the half marathon, and the RV ejection fraction was reduced, at 47 ± 5% compared with 60 ± 2% at baseline (P < .05). There were strong linear correlations between RV ejection fraction assessed by RT3DE and CMR at baseline and after the half marathon (r = 0.69 and r = 0.87, P < .01, respectively). CONCLUSIONS: Compared with CMR, RT3DE is a feasible and reproducible method of assessing transient RV dysfunction in athletes completing a half marathon.

Oxygen supplementation facilitating successful prosthetic fitting and rehabilitation of a patient with severe chronic obstructive pulmonary disease following trans-tibial amputation: a case report.

INTRODUCTION: Dysvascular amputations are increasingly performed in patients with underlying cardiac and pulmonary disorders. A limb prosthesis is rarely offered to patients with severe chronic obstructive pulmonary disease because of their inability to achieve the high energy expenditure required for prosthetic ambulation. We describe a case of successful prosthetic fitting and rehabilitation of a patient with severe chronic obstructive pulmonary disease with the aid of oxygen supplementation. CASE PRESENTATION: A 67-year-old aboriginal woman with severe chronic obstructive pulmonary disease and hypercapnic respiratory failure underwent right trans-tibial (below the knee) amputation for severe foot gangrene. An aggressive rehabilitation program of conditioning exercises and gait training utilizing oxygen therapy was initiated. She was custom-fitted with a right trans-tibial prosthesis. A rehabilitation program improved her strength, endurance and stump contracture, and she was able to walk for short distances with the prosthesis. The motion analysis studies showed a cadence of 73.5 steps per minute, a velocity of 0.29 meters per second and no difference in right and left step time and step length. CONCLUSION: This case report illustrates that patients with significant severe chronic obstructive pulmonary disease can be successfully fitted with limb prostheses and undergo rehabilitation using supplemental oxygen along with optimization of their underlying comorbidities. Despite the paucity of published information in this area, prosthesis fitting and rehabilitation should be considered in patients who have undergone amputation and have severe chronic obstructive disease.

A comparison of obese and nonobese people with asthma: exploring an asthma-obesity interaction.

OBJECTIVE: The objectives of our study were to compare patient characteristics and severity of disease in obese and normal-weight-confirmed people with asthma and to explore reasons for misdiagnosis of asthma, including potential interactions with obesity. METHODS: We randomly selected patients with physician-diagnosed asthma from eight Canadian cities. Asthma diagnosis was confirmed via a sequential lung function testing algorithm. Logistic analysis was conducted to compare obese and normal-weight-confirmed people with asthma and to assess characteristics associated with misdiagnosis of asthma. Interaction with obesity was investigated. RESULTS: Complete assessments were obtained on 496 subjects who reported physician-diagnosed asthma (242 obese and 254 normal-weight subjects); 346 had asthma confirmed with sequential lung testing, and in 150 subjects a diagnosis of asthma was ruled out. Obese subjects with asthma were significantly more likely to be men, have a history of hypertension and gastroesophageal reflux disease, and have a lower FEV(1) compared with normal-weight subjects with asthma. Older subjects, men, and subjects with higher FEV(1) were more likely to have received misdiagnoses of asthma. Obesity was not an independent predictor of misdiagnosis, however there was an interaction between obesity and urgent visits for respiratory symptoms. The odds ratio for receiving a misdiagnosis of asthma for obese individuals as compared with normal-weight individuals was 4.08 (95% CI, 1.23-13.5) for those with urgent visits in the past 12 months. CONCLUSIONS: Obese people with asthma have lower lung function and more comorbidities compared with normal-weight people with asthma. Obese individuals who make urgent visits for respiratory symptoms are more likely to receive a misdiagnosis of asthma.

Acute respiratory distress syndrome.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is characterised by a profound deterioration in systemic oxygenation or ventilation, or both, despite supportive respiratory therapy. ARDS is an acute and progressive respiratory disease of a non-cardiac cause that is associated with progressively diffuse bilateral pulmonary infiltrates, reduced pulmonary compliance, and hypoxaemia. The main causes of ARDS include direct lung injury (e.g., pneumonia, gastric acid aspiration) or indirect lung injury (e.g., sepsis, pancreatitis, massive blood transfusion, non-thoracic trauma). Sepsis and pneumonia account for about 60% of cases. Between one third and one half of people with ARDS die from the disease, but mortality depends on the underlying cause. Some survivors have long-term respiratory or cognitive problems. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions in adults with acute respiratory distress syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids, low tidal-volume mechanical ventilation, nitric oxide, prone position, and protective ventilation.

Critically ill patients with 2009 influenza A(H1N1) infection in Canada.

CONTEXT: Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America. OBJECTIVE: To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection. DESIGN, SETTING, AND PATIENTS: A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009. MAIN OUTCOME MEASURES: The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay. RESULTS: Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of Pao(2) to fraction of inspired oxygen [Fio(2)] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29). CONCLUSION: Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.

Cardiac imaging in myocardial sarcoidosis and other cardiomyopathies.

PURPOSE OF REVIEW: The clinical role of emerging imaging technologies for diagnosing cardiac sarcoidosis and other cardiomyopathies is evolving. An up-to-date review of the role of various imaging modalities in the evaluation of cardiac sarcoidosis and other cardiomyopathies is presented. RECENT FINDINGS: No study prospectively established the accuracy of each of the various techniques for diagnosing myocardial involvement in patients with suspected cardiac sarcoidosis. Cardiac magnetic resonance imaging (CMR) is demonstrated to have a sensitivity of 100% and specificity of approximately 80%, and positive predictive value of approximately 55% in diagnosing cardiac sarcoidosis. Recent studies have shown that 18F-2-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) has 100% sensitivity of detecting earlier stages of sarcoidosis. Both the FDG-PET and CMR may provide complementary information for the diagnosis and assessment of efficacy of therapy in patients with cardiac involvement from sarcoidosis. SUMMARY: Clinical and subclinical cardiac involvement is common among patients with sarcoidosis. A structured clinical assessment incorporating advanced cardiac imaging with CMR and FDG-PET scanning is more sensitive than the established clinical criteria. CMR is an established imaging modality in the diagnosis of various other cardiomyopathies. Well designed prospective clinical trials are awaited to define the exact role of these imaging studies in the diagnosis and guidance of therapy.

Relation of biomarkers and cardiac magnetic resonance imaging after marathon running.

Although previous studies including endurance athletes after marathon running have demonstrated biochemical evidence of cardiac injury and have correlated these findings with echocardiographic evidence of cardiac dysfunction, particularly of the right ventricle, a study of marathon athletes incorporating biomarkers, echocardiography, and cardiac magnetic resonance (CMR) imaging has not been performed to date. The aim of this study was to demonstrate the cardiac changes associated with participation in a marathon using serial cardiac biomarkers, echocardiography, and CMR imaging. Fourteen participants (mean age 33 +/- 6 years, 8 men) completed the full marathon. Myoglobin, creatine kinase, and troponin T were elevated in all athletes after the race. There was a strong linear correlation between right ventricular (RV) fractional area change as assessed by echocardiography and the RV ejection fraction as assessed by CMR imaging (r = 0.96) after the marathon. RV function, using echocardiography, transiently decreased from before to after the race (RV fractional area change 43 +/- 4% vs 33 +/- 5%, p <0.05). There were also postrace changes in left ventricular and RV diastolic filling. Although RV systolic changes were transient, left ventricular and RV diastolic abnormalities persisted up to 1 week after the marathon. No evidence of delayed enhancement of the left ventricular myocardium was found on CMR imaging, suggesting that the increase in cardiac biomarkers after the marathon may not have be due to myocardial necrosis. In conclusion, RV systolic dysfunction transiently occurs after a marathon and has been validated for the first time by CMR imaging. The increase in cardiac troponin after marathon running is likely due to the cytosolic release of the biomarker, not to the true breakdown of the myocyte, as confirmed by delayed enhancement CMR imaging.

Overdiagnosis of asthma in obese and nonobese adults.

BACKGROUND: It is unclear whether asthma is overdiagnosed in developed countries, particularly among obese individuals, who may be more likely than nonobese people to experience dyspnea. METHODS: We conducted a longitudinal study involving nonobese (body mass index 20-25) and obese (body mass index >/= 30) individuals with asthma that had been diagnosed by a physician. Participants were recruited from 8 Canadian cities by means of random-digit dialing. A diagnosis of current asthma was excluded in those who did not have evidence of acute worsening of asthma symptoms, reversible airflow obstruction or bronchial hyperresponsiveness, despite being weaned off asthma medications. We stopped asthma medications in those in whom a diagnosis of asthma was excluded and assessed their clinical outcomes over 6 months. RESULTS: Of 540 individuals with physician-diagnosed asthma who participated in the study, 496 (242 obese and 254 nonobese) could be conclusively assessed for a diagnosis of asthma. Asthma was ultimately excluded in 31.8% (95% confidence interval [CI] 26.3%-37.9%) in the obese group and in 28.7% (95% CI 23.5%-34.6%) in the nonobese group. Overdiagnosis of asthma was no more likely to occur among obese individuals than among nonobese individuals (p = 0.46). Of those in whom asthma was excluded, 65.5% did not need to take asthma medication or seek health care services because of asthma symptoms during a 6-month follow-up period. INTERPRETATION: About one-third of obese and nonobese individuals with physician-diagnosed asthma did not have asthma when objectively assessed. This finding suggests that, in developed countries such as Canada, asthma is overdiagnosed.

Antimicrobial management of sepsis and septic shock.

Every patient who has sepsis and septic shock must be evaluated appropriately at presentation before the initiation of antibiotic therapy. However, in most situations, an abridged initial assessment focusing on critical diagnostic and management planning elements is sufficient. Intravenous antibiotics should be administered as early as possible, and always within the first hour of recognizing severe sepsis and septic shock. Broad-spectrum antibiotics must be selected with one or more agents active against likely bacterial or fungal pathogens and with good penetration into the presumed source. Antimicrobial therapy should be reevaluated daily to optimize efficacy, prevent resistance, avoid toxicity, and minimize costs. Consider combination therapy in septic shock Pseudomonas infections in neutropenic patients. Combination therapy should be continued for no more than 3 to 5 days and de-escalation should occur following availability of susceptibilities. The duration of antibiotic therapy typically is limited to 7 to 10 days. Longer duration is considered if response is slow, if there is inadequate surgical source control, or if immunologic deficiencies are evident. Antimicrobial therapy should be stopped if infection is not considered the etiologic factor for a shock state.