Operational Challenges in Diagnosing Multi-Drug Resistant TB and Initiating Treatment in Andhra Pradesh, India

Revised National TB Control Programme (RNTCP), Andhra Pradesh, India. There is limited information on whether MDR-TB suspects are identified, undergo diagnostic assessment and are initiated on treatment according to the programme guidelines.To assess i) using the programme definition, the number and proportion of MDR-TB suspects in a large cohort of TB patients on first-line treatment under RNTCP ii) the proportion of these MDR-TB suspects who underwent diagnosis for MDR-TB and iii) the number and proportion of those diagnosed as MDR-TB who were successfully initiated on treatment.A retrospective cohort analysis, by reviewing RNTCP records and reports, was conducted in four districts of Andhra Pradesh, India, among patients registered for first line treatment during October 2008 to December 2009.Among 23,999 TB patients registered for treatment there were 559 (2%) MDR-TB suspects (according to programme definition) of which 307 (55%) underwent diagnosis and amongst these 169 (55%) were found to be MDR-TB. Of the MDR-TB patients, 112 (66%) were successfully initiated on treatment. Amongst those eligible for MDR-TB services, significant proportions are lost during the diagnostic and treatment initiation pathway due to a variety of operational challenges. The programme needs to urgently address these challenges for effective delivery and utilisation of the MDR-TB services

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine

Butyrylcholinesterase (BChE) is a plasma enzyme that catalyzes the hydrolysis of choline esters, including the muscle-relaxant succinylcholine and mivacurium. Patients who present sustained neuromuscular blockade after using succinylcholine usually carry BChE variants with reduced enzyme activity or an acquired BChE deficiency. We report here the molecular basis of the BCHE gene underlying the slow catabolism of succinylcholine in a patient who underwent endoscopic nasal surgery. We measured the enzyme activity of BChE and extracted genomic DNA in order to study the promoter region and all exons of the BCHE gene of the patient, her parents and siblings. PCR products were sequenced and compared with reference sequences from GenBank. We detected that the patient and one of her brothers have two homozygous mutations: nt1615 GCA > ACA (Ala539Thr), responsible for the K variant, and nt209 GAT > GGT (Asp70Gly), which produces the atypical variant A. Her parents and two of her brothers were found to be heterozygous for the AK allele, and another brother is homozygous for the normal allele. Sequence analysis of exon 1 including 5′UTR showed that the proband and her brother are homozygous for –116GG. The AK/AK genotype is considered the most frequent in hereditary hypocholinesterasemia (44%). This work demonstrates the importance of defining the phenotype and genotype of the BCHE gene in patients who are subjected to neuromuscular block by succinylcholine, because of the risk of prolonged neuromuscular paralysis

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears

Antimicrobial activity and brine shrimp toxicity of extracts of Terminalia brownii roots and stem

BACKGROUND: Ternimalia brownii Fresen (Combretaceae) is widely used in traditional medicine to treat bacterial, fungal and viral infections. There is a need to evaluate extracts of this plant in order to provide scientific proof for it's wide application in traditional medicine system. METHODS: Extraction of stem bark, wood and whole roots of T. brownii using solvents of increasing polarity, namely, Pet ether, dichloromethane, dichloromethane: methanol (1:1), methanol and aqua, respectively, afforded dry extracts. The extracts were tested for antifungal and antibacterial activity and for brine shrimp toxicity test. RESULTS: Extracts of the stem bark, wood and whole roots of T. brownii exhibited antibacterial activity against standard strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, and Bacillus anthracis and the fungi, Candida albicans and Cryptococcus neoformans. Aqueous extracts exhibited the strongest activity against both bacteria and fungi. Extracts of the roots and stem bark exhibited relatively mild cytotoxic activity against brine shrimp larvae with LC(50 )values ranging from 113.75–4356.76 and 36.12–1458.81 μg/ml, respectively. The stem wood extracts exhibited the highest toxicity against the shrimps (LC(50 )values 2.58–14.88 μg/ml), while that of cyclophosphamide, a standard anticancer drug, was 16.33 (10.60–25.15) μg/ml. CONCLUSION: These test results support traditional medicinal use of, especially, aqueous extracts for the treatment of conditions such as diarrhea, and gonorrhea. The brine shrimp results depict the general trend among plants of the genus Terminalia, which are known to contain cytotoxic compounds such as hydrolysable tannins. These results warrant follow-up through bioassay-directed isolation of the active principles

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein