Association of mitochondrial DNA copy number with metabolic syndrome and type 2 diabetes in 14 176 individuals.

BACKGROUND: Mitochondria play an important role in cellular metabolism, and their dysfunction is postulated to be involved in metabolic disturbances. Mitochondrial DNA is present in multiple copies per cell. The quantification of mitochondrial DNA copy number (mtDNA-CN) might be used to assess mitochondrial dysfunction. OBJECTIVES: We aimed to investigate the cross-sectional association of mtDNA-CN with type 2 diabetes and the potential mediating role of metabolic syndrome. METHODS: We examined 4812 patients from the German Chronic Kidney Disease (GCKD) study and 9364 individuals from the Cooperative Health Research in South Tyrol (CHRIS) study. MtDNA-CN was measured in whole blood using a plasmid-normalized qPCR-based assay. RESULTS: In both studies, mtDNA-CN showed a significant correlation with most metabolic syndrome parameters: mtDNA-CN decreased with increasing number of metabolic syndrome components. Furthermore, individuals with low mtDNA-CN had significantly higher odds of metabolic syndrome (OR = 1.025; 95% CI = 1.011-1.039, P = 3.19 × 10-4 , for each decrease of 10 mtDNA copies) and type 2 diabetes (OR = 1.027; 95% CI = 1.012-1.041; P = 2.84 × 10-4 ) in a model adjusted for age, sex, smoking and kidney function in the meta-analysis of both studies. Mediation analysis revealed that the association of mtDNA-CN with type 2 diabetes was mainly mediated by waist circumference in the GCKD study (66%) and by several metabolic syndrome parameters, especially body mass index and triglycerides, in the CHRIS study (41%). CONCLUSIONS: Our data show an inverse association of mtDNA-CN with higher risk of metabolic syndrome and type 2 diabetes. A major part of the total effect of mtDNA-CN on type 2 diabetes is mediated by obesity parameters.

Behaviours of concern following moderate to severe traumatic brain injury in individuals living in the community.

PRIMARY OBJECTIVE: Behaviours of Concern (BoC) following traumatic brain injury (TBI) have a significant negative impact on the daily functioning and quality of life for the individual and their family. However, there has been limited research examining the nature and severity of BoC beyond the acute recovery period, including the perspective of the individual with TBI as well as close others (COs). METHODS AND PROCEDURE: Eighty-nine individuals with predominantly severe TBI, at a mean of 11.4 years' post-injury, were identified through a no-fault accident compensation system database. Structured interviews were completed with 65 individuals with TBI, and 62 COs. Current BoC were documented using the Overt Behaviour Scale (OBS). MAIN OUTCOMES AND RESULTS: 70.5% of participants exhibited BoC on the OBS, with an average of 3 behaviours. Verbal aggression and socially inappropriate behaviour were the most common BoC. Self-report of behaviour change was endorsed by 81% of the sample. There was generally poor concordance between the perspectives of the individual with the TBI and their CO. CONCLUSION: Severe BoC, across multiple behaviour types, may be evident many years following predominantly severe TBI. There is a need to provide long-term behaviour support for these individuals.

A 16-week randomized controlled trial evaluating the physical activity guidelines for adults with spinal cord injury.

STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To evaluate the effectiveness of the physical activity guidelines (PAG) for adults with spinal cord injury (SCI) to improve aspects of physical fitness. SETTING: Community exercise facility. METHODS: Twenty-three participants (age: 40.4±11.6 years, C1-T11, 12.0±10.0 years post injury) were randomized into PAG training (n=12) or active control (CON, n=11) groups. PAG training was 2x per week for 16 weeks and involved 20 min of aerobic exercise at a moderate to vigorous intensity and three sets of 10 repetitions (at 50-70% 1 repetition maximum; 1RM). Pre- and post-testing included peak exercise and aerobic endurance tests on an arm ergometer and 1RM testing. RESULTS: Nineteen participants (PAG, n=11; CON, n=8) completed the 16-week training program and post-testing. There was a significant (P<0.05) increase in peak aerobic capacity (relative VO2peak: 17.2%, absolute VO2peak: 9.9%) and submaximal power output (26.3%) in the PAG group only. Increases in strength ranged from 11.5-38.9% and were significantly (P<0.05) different from CON for vertical bench press, seated row, and rickshaw press. Adherence to the exercise program was 85.2±8.3% for PAG, 44.4±34.3% for CON (P<0.01). CONCLUSION: The PAG for adults with SCI are sufficient to improve aspects of aerobic and muscular fitness and should be promoted as a means to improve physical capacity. SPONSORSHIP: Ontario Neurotrauma Foundation (ONF), Natural Sciences and Engineering Research Council (NSERC) of Canada.

A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila.

Humans sleep approximately a third of their lifetime. The observation that individuals with either long or short sleep duration show associations with metabolic syndrome and psychiatric disorders suggests that the length of sleep is adaptive. Although sleep duration can be influenced by photoperiod (season) and phase of entrainment (chronotype), human familial sleep disorders indicate that there is a strong genetic modulation of sleep. Therefore, we conducted high-density genome-wide association studies for sleep duration in seven European populations (N=4251). We identified an intronic variant (rs11046205; P=3.99 × 10(-8)) in the ABCC9 gene that explains ≈5% of the variation in sleep duration. An influence of season and chronotype on sleep duration was solely observed in the replication sample (N=5949). Meta-analysis of the associations found in a subgroup of the replication sample, chosen for season of entry and chronotype, together with the discovery results showed genome-wide significance. RNA interference knockdown experiments of the conserved ABCC9 homologue in Drosophila neurons renders flies sleepless during the first 3 h of the night. ABCC9 encodes an ATP-sensitive potassium channel subunit (SUR2), serving as a sensor of intracellular energy metabolism.

Direct referral and physical activity counselling upon discharge from spinal cord injury rehabilitation.

STUDY DESIGN: Sixteen-week follow-up study. OBJECTIVE: To evaluate the efficacy of referral from a health-care provider to regular exercise combined with 16 weeks of counselling support following discharge from inpatient or outpatient spinal cord injury (SCI) rehabilitation. SETTING: Two rehabilitation centres in Canada. METHODS: Seventeen participants (age 42.1±10.6 years, C3-T12, ASIA impairment score A-C) were recruited at discharge from inpatient (n=9; 5.2±1.3 months post-injury) or outpatient (n=8; 14.2±3.8 months post-injury) rehabilitation and were given a referral for regular exercise. Telephone counselling support was provided and adherence to the prescribed program was monitored for 16 weeks. RESULTS: There was a nonsignificant difference in exercise adherence rates (percentage of available sessions attended) between participants discharged from inpatient (71.4±44.9%) and those from outpatient (39.5±27.2%) rehabilitation programs. The most common barriers to participation were physical health problems (50%) and transportation (36%). An exercise beliefs questionnaire revealed that participants value exercise at discharge from rehabilitation, despite the common report of a relative lack of confidence in their ability to perform or adapt aerobic and resistance exercises to their specific capabilities. CONCLUSION: A system of direct referral and ongoing counselling support following discharge from either inpatient or outpatient SCI rehabilitation appears to encourage sustained participation, although future health promotion strategies should continue to provide specific information about how to adapt and complete aerobic and resistance exercises. SPONSORSHIP: Rick Hansen Institute and Ontario Neurotrauma Foundation.

Exercise equipment preferences among adults with spinal cord injury.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To evaluate exercise equipment preferences and compare cardiometabolic demand for passive hybrid and arm-only exercise among adults with paraplegia (PP) and those with tetraplegia (TP). SETTING: Four community exercise programmes. METHODS: Thirty-six adults (mean age: 41.1±12.1 years) with chronic (11.4±10.7 years post injury) TP (C3-C8; n=17) or PP (T3-T12; n=19) were recruited. Participants completed 20 min of submaximal aerobic exercise at moderate to vigorous intensity on four types of aerobic exercise equipment: arm cycle ergometer (ACE), arm glider (AG), arm-leg recumbent stepper (ALRS), and arm-leg cycle ergometer (ALCE). Participants also completed 3 sets of 10 repetitions of resistance exercise using wall pulleys (WP) and weight stack (WS) equipment. A questionnaire was administered to evaluate equipment preference. Heart rate (HR) and oxygen uptake (VO2) were measured in a subset of participants (n=9) during submaximal aerobic exercise. RESULTS: Arm-only exercise modes were perceived as being safer than passive hybrid exercise modes. There were no differences in perceived enjoyment between equipment types and groups. There were significant group but not equipment differences in HR (TP: 101.4 bpm; PP: 124.9 bpm) and VO2 (TP: 6.5 ml•kg(-1)•min(-1); PP: 10.5 mL•kg(-1)•min(-1)) during submaximal aerobic exercise. CONCLUSION: In this cross-community assessment of exercise equipment preferences after spinal cord injury (SCI), arm-only exercise modes were perceived as safer than hybrid exercise modes and there were no differences between equipment types in physiological responses.

Development of an evidence-informed leisure time physical activity resource for adults with spinal cord injury: the SCI Get Fit Toolkit.

OBJECTIVES: To systematically develop an evidence-informed leisure time physical activity (LTPA) resource for adults with spinal cord injury (SCI). SETTING: Canada. METHODS: The Appraisal of Guidelines, Research and Evaluation (AGREE) II protocol was used to develop a toolkit to teach and encourage adults with SCI how to make smart and informed choices about being physically active. A multidisciplinary expert panel appraised the evidence and generated specific recommendations for the content of the toolkit. Pilot testing was conducted to refine the toolkit's presentation. RESULTS: Recommendations emanating from the consultation process were that the toolkit be a brief, evidence-based resource that contains images of adults with tetraplegia and paraplegia, and links to more detailed online information. The content of the toolkit should include the physical activity guidelines (PAGs) for adults with SCI, activities tailored to manual and power chair users, the benefits of LTPA, and strategies to overcome common LTPA barriers for adults with SCI. The inclusion of action plans and safety tips was also recommended. CONCLUSION: These recommendations have resulted in the development of an evidence-informed LTPA resource to assist adults with SCI in meeting the PAGs. This toolkit will have important implications for consumers, health care professionals and policy makers for encouraging LTPA in the SCI community.

ALK rearrangements in EBUS-derived transbronchial needle aspiration cytology in lung cancer.

OBJECTIVES: Patients with non-small cell lung cancer (NSCLC) positive for anaplastic lymphoma kinase (ALK) gene rearrangements may be treated successfully with the ALK inhibitor crizotinib. ALK copy-number abnormalities have also been described. In this study, we evaluated the suitability of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to determine ALK status in endobronchial ultrasound (EBUS)-derived cytology samples. METHODS: Samples were obtained from 55 consecutive patients with NSCLC who had undergone EBUS-transbronchial needle aspiration (TBNA) according to our standard clinical protocols. All tumours had been screened previously for epithelial growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. FISH, using commercially available ALK rearrangement-specific probes, was employed to assess ALK status. IHC using the ALK-1 monoclonal antibody (DAKO) was also performed. RESULTS: FISH analysis was successful in 52 of 55 samples (94.5%); ALK rearrangement was demonstrated in 3 of 52 samples from patients with NSCLC (5.7%). ALK amplification was observed in 3 of 52 patient samples (5.7%) and an increase in ALK copy number was found in 28 of 52 patient samples (53.8%). IHC on cell blocks demonstrated ALK expression in one of three samples with ALK rearrangement. One patient sample had concomitant ALK rearrangement and KRAS mutation. CONCLUSIONS: We found FISH to be superior to IHC using the ALK-1 monoclonal antibody for the detection of ALK rearrangement in EBUS-TBNA cytology specimens in NSCLC, and also that ALK rearrangement can co-exist with KRAS mutation in the same tumour.

Pelagic to demersal transition in a coral-reef fish, the orbicular batfish Platax orbicularis.

Behavioural and ecological observations were made on young, reared Platax orbicularis in Opunohu Bay, Moorea, French Polynesia, during their transition from the pelagic, dispersive stage to the reef-orientated demersal stage. Seventy-two young P. orbicularis (17-75 mm standard length, LS ) were released in the pelagic zone and 20 (40-70 mm LS ) adjacent to the reefs. Swimming speed was slow (mean 5·2 cm s(-1) ) and independent of size. An ontogenetic descent was observed: the smallest P. orbicularis swam at the surface, medium-sized P. orbicularis swam in midwater (mean 5-13 m) and the largest P. orbicularis swam to the bottom, where many lay on their sides. Platax orbicularis swam southerly on average, away from the ocean and into the bay. Smaller P. orbicularis were more likely to swim directionally than larger individuals. Young P. orbicularis released near reef edges swam at similar, but more variable speeds (mean 6·6 cm s(-1) ). About half of those released near reefs swam away, but fewer swam away from an inshore fringing reef than from a patch reef near the bay mouth. Many P. orbicularis swam up the slope onto the reef top, but the little settlement observed was near the reef base. Average, near-reef swimming direction was also southerly. Some reef residents, in particular the triggerfish Balistapus undulatus, harassed young P. orbicularis.

Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology.

Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.

Muscle fatigue characteristics in paralyzed muscle after spinal cord injury.

STUDY DESIGN: The study design used is cross-sectional. OBJECTIVES: The aim of this study is to examine muscle contractile and excitability characteristics during fatigue of the tibialis anterior in six individuals with chronic spinal cord injury (SCI) and matched able-bodied (AB) controls. SETTING: McMaster University, Hamilton, ON, Canada. METHODS: Muscle compound action potential (M-wave) characteristics, muscle twitch properties, and summated force were examined during a 2 min fatigue protocol of intermittent bursts at 30 Hz (4 s tetanus, 2 s rest) or maximal voluntary contraction (MVC). Evoked twitch responses were followed during a recovery period. RESULTS: M-wave amplitude was smaller in SCI (2.5 ± 1.6 mV in SCI, 5.7 ± 3.2 mV in AB) at baseline, but there was no change in M-wave amplitude or area during fatigue in either group. There was an increase in M-wave duration toward the end of recovery in the SCI group. Peak torque (PT) was not different between groups at baseline (3.8 ± 1.8 Nm in SCI, 3.7 ± 0.6 Nm in AB); PT potentiated significantly during fatigue in the AB, but not SCI group. There was significantly greater fatigue of both PT (43% decline) and summated force (57% decline) in the SCI group compared with the AB group (13% increase and 22% decline for PT and MVC, respectively). CONCLUSION: The dorsiflexor muscles in people with SCI are significantly more fatiguable than those in AB controls, but decreases in muscle excitability do not seem to be an important contributor to the increased fatiguability. The mechanisms behind the increased fatigue must lie distal to the muscle membrane.

The effects of exercise training on physical capacity, strength, body composition and functional performance among adults with spinal cord injury: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVES: To conduct a systematic review of evidence surrounding the effects of exercise on physical fitness in people with spinal cord injury (SCI). SETTING: Canada. METHODS: The review was limited to English-language studies (published prior to March 2010) of people with SCI that evaluated the effects of an exercise intervention on at least one of the four main components of physical fitness (physical capacity, muscular strength, body composition and functional performance). Studies reported at least one of the following outcomes: oxygen uptake/consumption, power output, peak work capacity, muscle strength, body composition, exercise performance or functional performance. A total of 166 studies were identified. After screening, 82 studies (69 chronic SCI; 13 acute SCI) were included in the review. The quality of evidence derived from each study was evaluated using established procedures. RESULTS: Most studies were of low quality; however, the evidence was consistent that exercise is effective in improving aspects of fitness. There is strong evidence that exercise, performed 2-3 times per week at moderate-to-vigorous intensity, increases physical capacity and muscular strength in the chronic SCI population; the evidence is not strong with respect to the effects of exercise on body composition or functional performance. There were insufficient high-quality studies in the acute SCI population to draw any conclusions. CONCLUSIONS: In the chronic SCI population, there is good evidence that exercise is effective in improving both physical capacity and muscular strength, but insufficient quality evidence to draw meaningful conclusions on its effect on body composition or functional capacity.

The development of evidence-informed physical activity guidelines for adults with spinal cord injury.

OBJECTIVES: To systematically develop evidence-informed physical activity guidelines to improve physical fitness in people with spinal cord injury (SCI). SETTING: This study was conducted in Canada. METHODS: The Appraisal of Guidelines, Research and Evaluation II guideline development protocol was used to develop exercise guidelines to improve physical capacity and muscular strength. The evidence base for the guideline development process consisted of a systematic review and quality appraisal of research examining the effects of exercise on physical fitness among people with SCI. A multidisciplinary expert panel deliberated the evidence and generated the guidelines. Pilot testing led to refinement of the wording and presentation of the guidelines. RESULTS: The expert panel generated the following guidelines: for important fitness benefits, adults with a SCI should engage in (a) at least 20 min of moderate to vigorous intensity aerobic activity two times per week and (b) strength training exercises two times per week, consisting of three sets of 8-10 repetitions of each exercise for each major muscle group. CONCLUSION: People with SCI, clinicians, researchers and fitness programmers are encouraged to adopt these rigorously developed guidelines.

Factors influencing infection patterns of trophically transmitted parasites among a fish community: host diet, host-parasite compatibility or both?

Parasite infection patterns were compared with the occurrence of their intermediate hosts in the diet of nine sympatric fish species in a New Zealand lake. Stomach contents and infection levels of three gastrointestinal helminth species were examined from the entire fish community. The results highlighted some links between fish host diet and the flow of trophically transmitted helminths. Stomach contents indicated that all but one fish species were exposed to these helminths through their diet. Host feeding behaviour best explained infection patterns of the trematode Coitocaecum parvum among the fish community. Infection levels of the nematode Hedruris spinigera and the acanthocephalan Acanthocephalus galaxii, however, were not correlated with host diets. Host specificity is thus likely to modulate parasite infection patterns. The data indicate that host diet and host-parasite compatibility both contribute to the distribution of helminths in the fish community. Furthermore, the relative influence of encounter (trophic interactions between prey and predator hosts) and compatibility (host suitability) filters on infection levels appeared to vary between host-parasite species associations. Therefore, understanding parasite infection patterns and their potential impacts on fish communities requires determining the relative roles of encounter and compatibility filters within and across all potential host-parasite associations.

Comparison of droplet spread in standard and laminar flow operating theatres: SPRAY study group.

BACKGROUND: Reducing COVID-19 transmission relies on controlling droplet and aerosol spread. Fluorescein staining reveals microscopic droplets. AIM: To compare the droplet spread in non-laminar and laminar air flow operating theatres. METHODS: A 'cough-generator' was fixed to a theatre trolley at 45°. Fluorescein-stained 'secretions' were projected on to a series of calibrated targets. These were photographed under UV light and 'source detection' software measured droplet splatter size and distance. FINDINGS: The smallest droplet detected was ∼120 µm and the largest ∼24,000 µm. An average of 25,862 spots was detected in the non-laminar theatre, compared with 11,430 in the laminar theatre (56% reduction). The laminar air flow mainly affected the smaller droplets (<1000 µm). The surface area covered with droplets was: 6% at 50 cm, 1% at 2 m, and 0.5% at 3 m in the non-laminar air flow; and 3%, 0.5%, and 0.2% in the laminar air flow, respectively. CONCLUSION: Accurate mapping of droplet spread in clinical environments is possible using fluorescein staining and image analysis. The laminar air flow affected the smaller droplets but had limited effect on larger droplets in our 'aerosol-generating procedure' cough model. Our results indicate that the laminar air flow theatre requires similar post-surgery cleaning to the non-laminar, and staff should consider full personal protective equipment for medium- and high-risk patients.

The length-tension relationship of human dorsiflexor and plantarflexor muscles after spinal cord injury.

STUDY DESIGN: A cross-sectional design. OBJECTIVES: To examine the length-tension relationship of dorsiflexion (DF) and plantarflexion (PF) muscle groups in seven individuals with chronic spinal cord injury (SCI; C2-T7; age 43+/-10.1 years) and compare it with a group of age and sex-matched able-bodied (AB) controls. SETTING: McMaster University, Hamilton, ON, Canada. METHODS: Isometric single twitch properties, 0.5-s tetanic contractions (SCI) and maximal voluntary contractions (AB) were measured at nine joint angles from 20 degrees DF to 20 degrees PF. RESULTS: In the DF muscles, peak-evoked twitch (PT) torque occurred at 20 degrees PF for SCI (3.4+/-1.1 N m) and AB (3.8+/-1.4 N m) with no difference in peak torque between groups, whereas peak summated force occurred at 10 degrees PF in AB and 20 degrees PF in SCI (P<0.01). In the PF muscles, PT torque occurred at 15 degrees DF in AB (18.6+/-2.6 N m) and at 5 degrees DF (6.8+/-3.3 N m; P<0.01) in SCI, and peak-summated force occurred at 15 degrees DF in AB. The SCI group did not show any change in PF peak-summated force with varying joint angles. Rates of contraction and relaxation were not different between the two groups. CONCLUSIONS: The results suggest a significant change in the length-tension relationship of the PF muscles after SCI, but no change in the DF muscle group. Rehabilitation programs should focus on maintaining PF muscle length in order to optimize muscle strength and function after SCI.

Transsynaptic expression of a presynaptic glutamate receptor during hippocampal long-term potentiation.

Repetitive activation of excitatory synapses in the hippocampus produces a persistent enhancement of synaptic efficiency known as long-term potentiation (LTP). In anesthetized and in freely moving rats, the induction of LTP in the perforant path led to a transient increase in the amount of messenger RNA (mRNA) coding for a presynaptic glutamate receptor (GR33) in dentate granule cells. The amount of GR33 mRNA was increased for at least 5 hours after the induction of LTP but was indistinguishable from control values 1 day after induction. The N-methyl-D-aspartate receptor antagonist 2-aminophosphonovalerate prevented the induction of both LTP and the increase in GR33 mRNA. The amount of GR33 protein was increased in the mossy fiber terminal zone of dentate granule cells 5 hours after the induction of LTP. These results suggest that the induction of LTP in synapses at one stage in a neural network may lead to modification in synaptic function at the next stage in the network.

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Simple measures are as effective as invasive techniques in the diagnosis of pulmonary tuberculosis in Malawi.

SETTING: Detection of smear-positive pulmonary tuberculosis (PTB) cases is vital for tuberculosis (TB) control. Methods to augment sputum collection are available, but their additional benefit is uncertain in resource-limited settings. OBJECTIVE: To compare the diagnostic yields using five methods to obtain sputum from adults diagnosed with smear-negative PTB in Malawi. DESIGN: Self-expectorated sputum was collected under supervision for microscopy and mycobacterial culture in the study laboratory. Confirmed smear-negative patients provided physiotherapy-assisted sputum and induced sputum, followed the next morning by gastric washing and bronchoalveolar lavage (BAL) samples. RESULTS: A total of 150 patients diagnosed with smear-negative PTB by the hospital service were screened; 39 (26%) were smear-positive from supervised self-expectorated sputum examined in the study laboratory. The remaining 111 confirmed smear-negative patients were enrolled in the study; 89% were human immunodeficiency virus positive. Seven additional smear-positive cases were diagnosed using the augmented sputum collection techniques. No differences were observed in the numbers of cases detected using the different methods. Of the 46 smear-positive cases, 44 (95.6%) could be detected from self-expectorated and physiotherapy-assisted samples. CONCLUSIONS: For countries such as Malawi, the best use of limited resources to detect smear-positive PTB cases would be to improve the quality of self-expectorated sputum collection and microscopy. The additional diagnostic yield using BAL after induced sputum is limited.

Achalasia: an unusual cause of airway obstruction.

Achalasia is a disorder of the lower oesophageal sphincter and the smooth musculature of the oesophageal body. Although oesophageal obstruction is common, concurrent airway obstruction is exceptional. A case is presented of a 79-year-old woman admitted to the emergency department requiring intubation following out-of-hospital airway obstruction and subsequent respiratory arrest.