Intermolecular interactions underlie protein/peptide phase separation irrespective of sequence and structure at crowded milieu.

Liquid-liquid phase separation (LLPS) has emerged as a crucial biological phenomenon underlying the sequestration of macromolecules (such as proteins and nucleic acids) into membraneless organelles in cells. Unstructured and intrinsically disordered domains are known to facilitate multivalent interactions driving protein LLPS. We hypothesized that LLPS could be an intrinsic property of proteins/polypeptides but with distinct phase regimes irrespective of their sequence and structure. To examine this, we studied many (a total of 23) proteins/polypeptides with different structures and sequences for LLPS study in the presence and absence of molecular crowder, polyethylene glycol (PEG-8000). We showed that all proteins and even highly charged polypeptides (under study) can undergo liquid condensate formation, however with different phase regimes and intermolecular interactions. We further demonstrated that electrostatic, hydrophobic, and H-bonding or a combination of such intermolecular interactions plays a crucial role in individual protein/peptide LLPS.

p53 amyloid pathology is correlated with higher cancer grade irrespective of the mutant or wild-type form.

p53 (also known as TP53) mutation and amyloid formation are long associated with cancer pathogenesis; however, the direct demonstration of the link between p53 amyloid load and cancer progression is lacking. Using multi-disciplinary techniques and 59 tissues (53 oral and stomach cancer tumor tissue samples from Indian individuals with cancer and six non-cancer oral and stomach tissue samples), we showed that p53 amyloid load and cancer grades are highly correlated. Furthermore, next-generation sequencing (NGS) data suggest that not only mutant p53 (e.g. single-nucleotide variants, deletions, and insertions) but wild-type p53 also formed amyloids either in the nucleus (50%) and/or in the cytoplasm in most cancer tissues. Interestingly, in all these cancer tissues, p53 displays a loss of DNA-binding and transcriptional activities, suggesting that the level of amyloid load correlates with the degree of loss and an increase in cancer grades. The p53 amyloids also sequester higher amounts of the related p63 and p73 (also known as TP63 and TP73, respectively) protein in higher-grade tumor tissues. The data suggest p53 misfolding and/or aggregation, and subsequent amyloid formation, lead to loss of the tumor-suppressive function and the gain of oncogenic function, aggravation of which might determine the cancer grade.

Rust (Uromyces viciae-fabae Pers. de-Bary) of Pea (Pisum sativum L.): Present Status and Future Resistance Breeding Opportunities.

Uromyces viciae-fabae Pers. de-Bary is an important fungal pathogen causing rust in peas (Pisum sativum L.). It is reported in mild to severe forms from different parts of the world where the pea is grown. Host specificity has been indicated in this pathogen in the field but has not yet been established under controlled conditions. The uredinial states of U. viciae-fabae are infective under temperate and tropical conditions. Aeciospores are infective in the Indian subcontinent. The genetics of rust resistance was reported qualitatively. However, non-hypersensitive resistance responses and more recent studies emphasized the quantitative nature of pea rust resistance. Partial resistance/slow rusting had been described as a durable resistance in peas. Such resistance is of the pre-haustorial type and expressed as longer incubation and latent period, poor infection efficiency, a smaller number of aecial cups/pustules, and lower units of AUDPC (Area Under Disease Progress Curve). Screening techniques dealing with slow rusting should consider growth stages and environment, as both have a significant influence on the disease scores. Our knowledge about the genetics of rust resistance is increasing, and now molecular markers linked with gene/QTLs (Quantitative Trait Loci) of rust resistance have been identified in peas. The mapping efforts conducted in peas came out with some potent markers associated with rust resistance, but they must be validated under multi-location trails before use in the marker-assisted selection of rust resistance in pea breeding programs.

Direct Demonstration of Seed Size-Dependent α-Synuclein Amyloid Amplification.

The size of amyloid seeds is known to modulate their autocatalytic amplification and cellular toxicity. However, the seed size-dependent secondary nucleation mechanism, toxicity, and disease-associated biological processes mediated by α-synuclein (α-Syn) fibrils are largely unknown. Using the cellular model and in vitro reconstitution, we showed that the size of α-Syn fibril seeds dictates not only their cellular internalization and associated cell death but also the distinct mechanisms of fibril amplification pathways involved in the pathological conformational change of α-Syn. Specifically, small fibril seeds showed elongation possibly through monomer addition at the fibril termini, whereas longer fibrils template the fibril amplification by surface-mediated nucleation as demonstrated by super-resolution microscopy. The distinct mechanism of fibril amplification and cellular uptake along with toxicity suggest that breakage of fibrils into seeds of different sizes determines the underlying pathological outcome of synucleinopathies.

Gene-Based Resistance to Erysiphe Species Causing Powdery Mildew Disease in Peas (Pisum sativum L.).

Globally powdery mildew (PM) is one of the major diseases of the pea caused by Erysiphe pisi. Besides, two other species viz. Erysiphe trifolii and Erysiphe baeumleri have also been identified to infect the pea plant. To date, three resistant genes, namely er1, er2 and Er3 located on linkage groups VI, III and IV respectively were identified. Studies have shown the er1 gene to be a Pisum sativum Mildew resistance Locus 'O' homologue and subsequent analysis has identified eleven alleles namely er1-1 to er1-11. Despite reports mentioning the breakdown of er1 gene-mediated PM resistance by E. pisi and E. trifolii, it is still the most widely deployed gene in PM resistance breeding programmes across the world. Several linked DNA markers have been reported in different mapping populations with varying linkage distances and effectiveness, which were used by breeders to develop PM-resistant pea cultivars through marker assisted selection. This review summarizes the genetics of PM resistance and its mechanism, allelic variations of the er gene, marker linkage and future strategies to exploit this information for targeted PM resistance breeding in Pisum.

Heat stress tolerance in peas (Pisum sativum L.): Current status and way forward.

In the era of climate change, the overall productivity of pea (Pisum sativum L.) is being threatened by several abiotic stresses including heat stress (HS). HS causes severe yield losses by adversely affecting several traits in peas. A reduction in pod yield has been reported from 11.1% to 17.5% when mean daily temperature increase from 1.4 to 2.2°C. High-temperature stress (30.5-33°C) especially during reproductive phase is known to drastically reduce both seed yield and germination. HS during germination and early vegetative stage resulted in poor emergence and stunted plant growth along with detrimental effects on physiological functions of the pea plant. To combat HS and continue its life cycle, plants use various defense strategies including heat escape, avoidance or tolerance mechanisms. Ironically, the threshold temperatures for pea plant and its responses are inconsistent and not yet clearly identified. Trait discovery through traditional breeding such as semi leaflessness (afila), upright growing habit, lodging tolerance, lower canopy temperature and small seeded nature has highlighted their utility for greater adaptation under HS in pea. Screening of crop gene pool and landraces for HS tolerance in a targeted environment is a simple approach to identify HS tolerant genotypes. Thus, precise phenotyping using modern phenomics tools could lead to increased breeding efficiency. The NGS (next generation sequencing) data can be associated to find the candidate genes responsible for the HS tolerance in pea. In addition, genomic selection, genome wide association studies (GWAS) and marker assisted selection (MAS) can be used for the development of HS tolerant pea genotypes. Additionally, development of transgenics could be an alternative strategy for the development of HS tolerant pea genotypes. This review comprehensively covers the various aspects of HS tolerance mechanisms in the pea plant, screening protocols, omic advances, and future challenges for the development of HS tolerant genotypes.

De novo transcriptome analysis provides insights into formation of in vitro adventitious root from leaf explants of Arnebia euchroma.

BACKGROUND: Adventitious root formation is considered a major developmental step during the propagation of difficult to root plants, especially in horticultural crops. Recently, adventitious roots induced through plant tissue culture methods have also been used for production of phytochemicals such as flavonoids, anthocyanins and anthraquinones. It is rather well understood which horticultural species will easily form adventitious roots, but the factors affecting this process at molecular level or regulating the induction process in in vitro conditions are far less known. The present study was conducted to identify transcripts involved in in vitro induction and formation of adventitious roots using Arnebia euchroma leaves at different time points (intact leaf (control), 3 h, 12 h, 24 h, 3 d, 7 d, 10 d and 15 d). A. euchroma is an endangered medicinal Himalayan herb whose root contains red naphthoquinone pigments. These phytoconstituents are widely used as an herbal ingredient in Asian traditional medicine as well as natural colouring agent in food and cosmetics. RESULTS: A total of 137.93 to 293.76 million raw reads were generated and assembled to 54,587 transcripts with average length of 1512.27 bps and N50 of 2193 bps, respectively. In addition, 50,107 differentially expressed genes were identified and found to be involved in plant hormone signal transduction, cell wall modification and wound induced mitogen activated protein kinase signalling. The data exhibited dominance of auxin responsive (AUXIN RESPONSE FACTOR8, IAA13, GRETCHEN HAGEN3.1) and sucrose translocation (BETA-31 FRUCTOFURANOSIDASE and MONOSACCHARIDE-SENSING protein1) genes during induction phase. In the initiation phase, the expression of LATERAL ORGAN BOUNDARIES DOMAIN16, EXPANSIN-B15, ENDOGLUCANASE25 and LEUCINE-rich repeat EXTENSION-like proteins was increased. During the expression phase, the same transcripts, with exception of LATERAL ORGAN BOUNDARIES DOMAIN16 were identified. Overall, the transcriptomic analysis revealed a similar patterns of genes, however, their expression level varied in subsequent phases of in vitro adventitious root formation in A. euchroma. CONCLUSION: The results presented here will be helpful in understanding key regulators of in vitro adventitious root development in Arnebia species, which may be deployed in the future for phytochemical production at a commercial scale.

In vitro adventitious roots: a non-disruptive technology for the production of phytoconstituents on the industrial scale.

The current trends of consumer-driven demands for natural therapeutics and the availability of evidence-based phytopharmaceuticals from traditional knowledge has once again brought the medicinal plants into forefront of health. In 2019, World Health Organization global report on traditional and complementary medicine has also substantiated the revival of herbal medicine including its convergence with conventional medicine for the management and prevention of diseases. It means these industries need plenty of plant materials to meet the unprecedented demands of herbal formulations. However, it is pertinent to mention here that around 70-80% medicinal plants are sourced from the wild and most of such highly acclaimed plants are listed under Rare, Endangered and Threatened species by IUCN. Additionally, over 30% traditional health formulations are based on underground plant parts, which lead to the uprooting of plants. Overharvesting from limited plant populations, meager conventional cultivation and a rising fondness for natural products exerting enormous pressure on natural habitats. Therefore, the nondestructive means of phytochemical production employing biotechnological tools could be used for sustainable production and consumption patterns. In recent years, a number of reports described the use of adventitious roots induced under in vitro conditions for the extraction of phytochemicals on a sustainable basis. In this article, efforts are made to review recent developments in this area as well as understand the induction mechanisms of adventitious roots, their in vitro cultivation, probable factors that affect the growth and metabolite production, and assess the possibility of industrial scale production to meet the rising demands of natural herbs.

Insights into the Host-Pathogen Interaction Pathways through RNA-Seq Analysis of Lens culinaris Medik. in Response to Rhizoctonia bataticola Infection.

Dry root rot (Rhizoctonia bataticola) is an important disease of lentils (Lens culinaris Medik.).To gain an insight into the molecular aspects of host-pathogen interactions, the RNA-seq approach was used in lentils following inoculation with R.bataticola. The RNA-Seq has generated >450 million high-quality reads (HQRs) and nearly 96.97% were properly aligned to the reference genome. Very high similarity in FPKM (fragments per kilobase of exon per million mapped fragments) values (R > 0.9) among biological replicates showed the consistency of the RNA-Seq results. The study revealed various DEGs (differentially expressed genes) that were associated with changes in phenolic compounds, transcription factors (TFs), antioxidants, receptor kinases, hormone signals which corresponded to the cell wall modification enzymes, defense-related metabolites, and jasmonic acid (JA)/ethylene (ET) pathways. Gene ontology (GO) categorization also showed similar kinds of significantly enriched similar GO terms. Interestingly, of the total unigenes (42,606), 12,648 got assembled and showed significant hit with Rhizoctonia species. String analysis also revealed the role of various disease responsive proteins viz., LRR family proteins, LRR-RLKs, protein kinases, etc. in the host-pathogen interaction. Insilico validation analysis was performed using Genevestigator® and DEGs belonging to six major defense-response groups viz., defense-related enzymes, disease responsive genes, hormones, kinases, PR (pathogenesis related) proteins, and TFs were validated. For the first time some key miRNA targets viz. miR156, miR159, miR167, miR169, and miR482 were identified from the studied transcriptome, which may have some vital role in Rhizoctonia-based responses in lentils. The study has revealed the molecular mechanisms of the lentil/R.bataticola interactions and also provided a theoretical approach for the development of lentil genotypes resistant to R.bataticola.

Customization of attachments in tooth supported overdentures: Three clinical reports.

In elderly patients with few remaining teeth, overdenture is a good treatment option. Roots beneath the denture protect the alveolar ridge, offer proprioception and improve retention, stability and masticatory efficiency of dentures. Customization of attachments available is a viable alternative for some patients in which prefabricated attachments cannot be placed or in which cost is a factor; to improve the final outcome of the treatment. Due to competitive commercialization, implant treatment has become the norm in current dentistry and the concept of tooth supported overdentures has eclipsed, but with proper case selection, thorough treatment planning and modifications in the denture such as customization of attachments, amalgam stops, cross-linked teeth, and metallic mesh can be applied to prolong the longevity and success of the attachment overdenture prosthesis.

Development and characterization of penta-flowering and triple-flowering genotypes in garden pea (Pisum sativum L. var. hortense).

This study reports the development of a garden pea genotype 'VRPM-901-5' producing five flowers per peduncle at multiple flowering nodes, by using single plant selection approach from a cross 'VL-8 × PC-531'. In addition, five other stable genetic stocks, namely VRPM-501, VRPM-502, VRPM-503, VRPM-901-3 and VRPSeL-1 producing three flowers per peduncle at multiple flowering nodes were also developed. All these unique genotypes were of either mid- or late- maturity groups. Furthermore, these multi-flowering genotypes were identified during later generations (F4 onward), which might be because of fixation of certain QTLs or recessive gene combinations. Surprisingly, a common parent PC-531, imparting multi-flowering trait in ten cross combinations was identified. Thus, the genotype PC-531 seems to harbor some recessive gene(s) or QTLs that in certain combination(s) express the multi-flowering trait. The interaction between genotype and environment showed that temperature (11-20°C) plays a key role in expression of the multi-flowering trait besides genetic background. Furthermore, the possible relationship between various multi-flowering regulatory genes such as FN, FNA, NEPTUNE, SN, DNE, HR and environmental factors was also explored, and a comprehensive model explaining the multi-flowering trait in garden pea is proposed.

Assessment of treatment response to splint therapy and evaluation of TMJ function using joint vibration analysis in patients exhibiting TMJ disc displacement with reduction: A clinical study.

Context, Aim, and Objectives: Diagnosis of temporomandibular joint (TMJ) disc displacement with reduction (DDR) is difficult. Literature combining different subjective parameters of TMJ function with an objective evaluation of TMJ function using joint vibration analysis (JVA) is limited. Hence, the study was planned to diagnose temporomandibular disorder accurately, to do a subjective and objective evaluation of TMJ function, and to assess the effectiveness of different types of splint therapy over the conventional anterior repositioning appliance (ARA) group. DESIGN: Single-blind, randomized, comparative clinical trial conducted in thirty patients, 18-55 years of age, allocated to three groups, i.e., ARA conventional group, centric stabilization splint (CSS), and Soft splint (SS) groups. SUBJECTS AND METHODS: Preoperative values of comfortable mouth opening (CMO) in mm, maximum mouth opening (MMO) in mm, TMJ clicking and tenderness (grading 0-3), visual analog scale pain score (0-10 cm), and total energy (TE) integral values of both TMJs using JVA were recorded. Postoperative values were taken at the time of delivery of splint at 1st, 2nd, 6th, and 10th week. Statistical Analysis and Results: Intergroup comparison - Kruskal-Wallis test showed no statistically significant difference in CMO, MMO, and TE values of right TMJs among three groups at any point. No significant difference was seen in TMJ clicking and tenderness among groups at any point of time except at 10 weeks and at 2 weeks, respectively, by Chi-square test. Intragroup comparison - Wilcoxon signed-rank test showed the significance of difference (P < 0.05*) in postoperative visits for CMO, MMO, pain score, and TE values. Clinical effect size, extent, consistency, and percentage of cases showing improvement were maximum for CSS group. CONCLUSIONS: The study concludes that the use of JVA for diagnosis along with history and clinical examination increases the accuracy of the diagnosis of DDR. ARA group was used as a conventional treatment option. Although statistically significant difference in pre- and post-treatment values was obtained in all the three groups, CSS group patients showed consistent clinically effective responses and more significant improvement in the subsequent follow-up visits than SS group. Hence, it is advisable to start therapy with CSS splint in TMJ DDR patients to get sooner and effective results without minimum side effects.

Esthetic Rehabilitation of Anterior Teeth with Copy-Milled Restorations: A Report of Two Cases.

Digitalization has become part and parcel of contemporary prosthodontics with the probability of most of the procedures being based on the digital techniques in the near future. This digital revolution started in the latter half of the 20th century by converting analog objects/signals into digital bits and bytes. Recent developments in all-ceramic materials and systems of computer-aided designing and computer-aided manufacturing (CAD/CAM), copy milling, and so forth offer excellent esthetics and superb biocompatibility. Copy milling system for ceramics enables milling of the zirconia cores of all-ceramic restorations precisely and also if this system is properly used the procedure for fabricating all-ceramic restorations can be substantially simplified. This case report presents fabrication of all-ceramic Maryland Bridge and post-core with a copy milling system for esthetics and preservation of integrity of tooth. For both of the patients, the use of biologic, all-ceramic, copy-milled restorations resulted in clinical success and recovered function and esthetics.

Analgesic Efficacy of Ultrasound Guided FICB in Patients with Hip Fracture.

INTRODUCTION: Hip fractures are often encountered in the elderly and present special problems to the anaesthesiologist. Fascia iliaca compartment block is another technique with the intent to block all the three nerves like 3-in-1 nerve block. AIM: To evaluate the analgesic efficacy of ultrasound guided fascia iliaca compartment block to facilitate positioning of patients with hip fracture for spinal anaesthesia. MATERIALS AND METHODS: This prospective study was conducted in 50 patients aged between 40-80 years, belonging to American Society of Anesthesiologists (ASA) physical status I-III undergoing surgery for hip fracture. All 50 patients received an ultrasound guided Fascia Iliaca Compartment Block (FICB) in the premedication room with 30 mL of 0.5% ropivacaine by 23G spinal needle. Sensory blockade was evaluated 5, 10 and 20 minutes after ropivacaine administration using loss of perception to cold in the lateral, anterior and medial part of the thigh. Visual analogue scale scores were noted before the block, 20 minutes after block and during positioning for spinal anaesthesia. Patient's acceptance for FICB was evaluated 24 hour after arriving back to the orthopaedics ward using a two-point score. Any episode of hypotension or bradycardia was noted and managed accordingly. RESULTS: In lateral part of thigh, at 5 minutes sensory blockade was present in 33 patients (66%) and at 10 minutes sensory blockade was present in 45 cases (90%). In anterior part of thigh, sensory blockade was present in 34 cases (68%) at 5 minutes time interval and at 10 minutes sensory blockade was present in 48 cases (96%). In medial part of thigh, 28 cases (56%) had sensory blockade at 5 minutes and at 10 minutes in 43 cases (86%). Sensory blockage was same at 20 minutes as on 10 minutes interval in all thigh parts. Before FIC block average VAS was 7.5 which was decreased to average of 2.94 at 20 minutes after block which was statistically significant (p<0.01). During positioning for spinal anaesthesia, 46 patients had VAS less than 4. Positioning during spinal anaesthesia was assessed unsatisfactory (0) in 2 cases (4%), satisfactory (1) in 5 cases (10%), good (2) in 25 cases (50%) and excellent (3) in 18 cases (36%). CONCLUSION: Ultrasound guided FICB can be performed safely without complications in controlling pain for patients with hip fracture. Performing an FICB before positioning for spinal anaesthesia provides good pain management and facilitates spinal performance with wide patient acceptance, hence improving overall quality and efficiency of care.

A Novel Approach to Treat Traumatized Alveolar Ridges: Two Case Reports.

Functional forces are transmitted to the basal seat mucosa through a hard denture base during mastication. Such hard base dentures are not comfortably tolerated in patients with fragile oral mucosa and will cause sore spots, masticatory pain, and further resorption of alveolar bone. Soft liners materials can be advocated successfully to manage such clinical situations. The soft liner material absorbs masticatory forces by means of the cushioning effect and distributes occlusal forces uniformly to prevent trauma to compromised residual ridges.

Concurrent sensitization to Aspergillus Fumigatus in tropical pulmonary eosinophilia.

Tropical pulmonary eosinophilia (TPE) is characterized by lung tissue and peripheral blood eosinophilia. Serum total IgE is also markedly increased in TPE. However, an association with asthma or other hypersensitivity conditions has not been described. During the diagnostic workup of three patients eventually confirmed to have TPE, hypersensitivity to the fungus, Aspergillus Fumigatus was found. However, there was no evidence of diseases of aspergillus hypersensitivity such as severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA). This association however raises the possibility of a future risk of these potentially serious allergic respiratory manifestations.

Implant success lies in complications management: A report of two cases.

At present, implant supported or retained prostheses are considered as a first therapeutic alternative for patients. Although the success rate of dental implants is very high, no treatment is without complications; same applies to implants also. Implant failure can be due to biological factors, i.e., loss of osseointegration or due to technical complications. This case report presents implant complications involving both factors along with the management of these cases. In implant supported overdenture patient, loss of implant on the right side and implant body fracture of the left side implant is reported and in another patient abutment screw fracture and its management is reported.

Occupational emphysema following long-term exposure to metal fumes during electroplating in a non-smoker.

Exposure to cigarette smoke is by far the most common causative factor for chronic obstructive pulmonary disease. Occupational exposure to fumes, chemicals, dusts and environmental pollution is also an important cause of chronic productive cough. Emphysema developing as a consequence of an occupational exposure is extremely rare. We describe the rare occurrence of severe emphysema in a non-smoker male who had worked for nearly three decades in nickel electroplating industry.

Cardiac Sympathetic Dominance and Systemic Inflammation in COPD.

Cardiac autonomic dysfunction is an independent determinant of adverse outcomes in many diseases. The available literature on the relative changes in sympathetic and parasympathetic components in chronic obstructive pulmonary disease (COPD) is equivocal, the clinical and physiological correlates are poorly defined and association with markers of systemic inflammation has not been explored. As both autonomic dysfunction and systemic inflammation may contribute to cardiovascular morbidity in COPD, we hypothesized that these may be associated. Sixty three stable patients of COPD and 36 controls underwent spirometry, estimation of diffusion capacity, six-minute walk test and measurements of serum interleukin-6 (IL-6) and high-sensitivity C-Reactive protein. Cardiac autonomic activity was evaluated by standard five-minute heart rate variability (HRV) recordings to obtain time- and frequency-domain indices and the averaged heart rate. We observed that HRV indices of overall autonomic modulation, the standard deviation of time intervals between consecutive normal beats (SDNN) and total power, were greater in patients with higher levels of indices of both parasympathetic and sympathetic activity. The heart rate was significantly higher in patients indicating an overall sympathetic dominance and was inversely correlated with diffusion capacity. Serum IL-6 was inversely correlated with pNN50, an index of parasympathetic activity, and positively with LF/HF ratio, a measure of sympathetic: parasympathetic balance. None of the HRV indices was significantly correlated with physiological measures of severity. It was concluded that patients with COPD have increased cardiac autonomic modulation with sympathetic dominance. This is associated with decreased lung diffusion capacity and systemic inflammation.

Acute exacerbations of chronic obstructive pulmonary disease: causes and impacts.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are recognised clinically as episodes of increased breathlessness and productive cough requiring a more intensive treatment. A subset of patients with this disease is especially prone to such exacerbations. These patients are labelled as 'frequent exacerbators'. Though yet poorly characterised in terms of host characteristics, including any genetic basis, these patients are believed to represent a distinct phenotype as they have a different natural history with a more progressive disease and a poorer prognosis than those who get exacerbations infrequently. Most exacerbations appear to be associated with infective triggers, either bacterial or viral, although 'non-infective' agents, such as air pollution and other irritants may also be important. Susceptibility to exacerbations is determined by multiple factors. Several risk factors have been identified, some of which are modifiable. Chronic obstructive pulmonary disease (COPD) exacerbations are major drivers of health status and patient-centered outcomes, and are a major reason for health care utilisation including hospitalisations and intensive care admissions. These are associated with considerable morbidity and mortality, both immediate and long-term. These episodes have a negative impact on the patient and the disease including high economic burden, increased mortality, worsening of health status, limitation of activity, and aggravation of comorbidities including cardiovascular disease, osteoporosis and neuro-psychiatric complications. Exacerbations also increase the rate of progression of disease, increasing the annual decline in lung function and leading to a poorer prognosis. Evaluation of risk of exacerbations is now included as a major component of the initial assessment of a patient with COPD in addition to the traditionally used lung function parameter, forced expiratory volume in one second (FEV1). Decreasing the risk of exacerbations and their prevention is a major therapeutic goal of management in COPD.