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Background The Mycobacterium abscessus complex (MABC) is a difficult to treat mycobacterium with two distinct morphologies: smooth and rough. As the clinical implications are unclear, we explored the morphology of MABC in relation to disease and outcome. Methods We performed a retrospective multicenter cohort study including patients with confirmed MABC in Sweden, 2009–2020, with treatment outcome as the primary outcome. MABC colony morphology was determined by light microscopy on Middlebrook 7H10 agar plates. Results Of the 71 MABC isolates, a defined morphology could be determined for 63 isolates, of which 40 were smooth (56%) and 23 were rough (32%). Immunosuppression, pulmonary disease, and cavitary lesion on chest radiographs were significantly associated with a rough isolate morphology. Participants with smooth isolates had more favorable treatment outcomes (12/14, 86%) compared to those with rough isolates (3/10, 30%). In an age-adjusted logistic regression, rough morphology of MABC was associated to lower odds of clinical cure compared to smooth morphology (adjusted odds ratio, 0.12; P = .049). Conclusions Study participants with rough MABC colony morphology of isolates had a worse clinical outcome compared to those with smooth isolates. The biological mechanisms should be further characterized and colony morphology of MABC taken into account during clinical management.

Infection has been proposed as a cause of back pain in individuals with Modic changes. This review summarises the knowledge on this topic in Scandinavia. A Norwegian randomized controlled trial could not replicate results in favor of antibiotic treatment for such patients. A Danish study demonstrated that patients with low back pain and Modic changes had similar physical disability-scores and less sick leave due to back pain than individuals without Modic changes at long-term follow-up (10 years). A Swedish study displayed equal bacterial presence in discs of patients operated for lumbar disc herniation and in control patients, indicating that the presence of bacteria is caused by contamination during the surgical procedure and is not related to back pain.

Infection has been proposed as a cause of back pain in individuals with Modic changes. This review summarises the knowledge on this topic in Scandinavia. A Norwegian randomized controlled trial could not replicate results in favor of antibiotic treatment for such patients. A Danish study demonstrated that patients with low back pain and Modic changes had similar physical disability-scores and less sick leave due to back pain than individuals without Modic changes at long-term follow-up (>10 years). A Swedish study displayed equal bacterial presence in discs of patients operated for lumbar disc herniation and in control patients, indicating that the presence of bacteria is caused by contamination during the surgical procedure and is not related to back pain.

This report is based on results from three research groups in Sweden (Fritzell et al), Denmark (Udby et al), and Norway (Bråten et al). The groups have conducted studies published in international journals in 2019 [8-10]. The results complement each other and strongly suggest that antibiotics, in the absence of clear signs of a clinically relevant infection (discitis/spondylitis), should not be used for back pain with or without leg pain. The Swedish study showed that bacteria found in the disc/vertebra during surgery are very likely due to contamination [8], the Danish study showed that patients with Modic Changes (MC) on MR in the long term were not associated with more back pain or functional impairment than in patients without MC [9], and the Norwegian study showed that antibiotics for residual back pain after previous disc herniation had no better clinical effect than placebo [10]. Antibiotic resistance is one of the biggest threats to public health today and in the future.

Cystic fibrosis (CF) is a genetic disease leading to chronic bacterial airway infection and inflammation. T helper 17 (Th17) cells are identified by their production of interleukin (IL)-17A, which recruit neutrophils to the site of airway infection. IL-23 is an important inducer of IL-17 and IL-22 production. The aim of this study was to study the role of Th17 cells in CF airway infection by measuring the levels of Th17 associated cytokines in sputum from CF patients with or without airway infection and by comparison with non-CF-controls. In a cross-sectional screening study, cytokine levels were measured with a Th17 multiplex cytokine ELISA. Significantly lower levels of IL-17A and IL-23 were found in sputa from infected CF patients. The lowest levels of IL-17A were found in patients chronically infected with P. aeruginosa, which also had the lowest IL-17/IL-22 ratio, while children had a higher ratio. Children also had higher IL-23 levels than adults. IL-1ß and IL-10 were significantly lower in CF sputum compared to controls. Thus, in our study CF patients with chronic infections had a lower production of Th17 associated cytokines in sputum compared with non-infected CF patients and infected patient without CF.

Antibiotics have been suggested as treatment for selected patients with chronic back pain, with or without leg pain, and in association with Modic changes type 1 (MC1) on MRI (Modic et al. 1988, Albert et al. 2013a). The hypothesis is that various bacteria, but above all the common skin bacterium Cutibacterium acnes (formerly Propionibacterium acnes), would spread hematogenously to degenerated discs, where a “low-grade subclinical infection” would trigger an inflammatory reaction and cause MC1 (Albert et al. 2013a), irritate nociceptive nerve endings, and induce pain. Other studies have not found this connection, or have been cautious in their conclusions (Birkenmaier 2013, Urquhart et al. 2015) but have not had the same public impact. Since back/leg pain is common, and Modic changes occur in people with or without back/leg pain (Wang et al. 2012), and as antibiotic resistance is a major health threat (Carlsson et al. 2019), the suggestion of treating chronic back/leg pain with antibiotics must be thoroughly investigated. Research groups in Sweden, Denmark, and Norway have independently conducted studies from 3 different perspectives, but with a focus on the same basic questions: is there a causative link between Modic changes, back pain, and bacteria. The studies, all published during 2019, conclude that antibiotics should not be used for back/leg pain, unless there is a clinically relevant infection in the disc/vertebra (discitis/spondylitis).

Previous studies have identified patients infected with Mycobacterium chimaera (M. chimaera) subsequent to cardiac surgery. Water tanks in heater-cooler units (HCUs) used cardiac heart surgery was traced as source. The aim was to investigate occurrence of M. chimaera and other microorganisms in HCUs and evaluate the silver-ion cleaning routine.Five HCUs were disinfected with silver-ions and examined for mycobacteria directly (15 min) after the disinfection procedures and later on three occasions (3, 6, 10 weeks). One HCU was selected for additional investigation of the presence of other microorganisms. In addition, tap water from five sinks in the surgical department was examined for the presence of mycobacteria and other microorganisms.M. chimaera grew in all the HCU water tanks and in 35 of the 40 HCU samples. Three of the samples also contained Mycobacterium gordonae. When the selected HCU tanks were analysed directly after the disinfection procedure bacteria and fungi were found but no non-fermenting Gram-negative rods. These HCU samples contained a doubled to 3 fold amount of bacteria compared to initial tap water samples. No mycobacteria were found in any sample from the five water taps.The silver-ion cleaning routine was insufficient and M. chimaera was found in all HCUs. However, no mycobacteria were found in any sample from the five water taps suggesting another source of colonization. It is probable that residual water and biofilm are of importance. Our results emphasize the need for improved disinfection procedures and improved construction of the HCUs.

Background: Low back pain (LBP) with or without lumbar disc herniation (LDH) is one of the most commonly found symptoms worldwide. The etiology is often unclear, but a low-grade infection caused by the anaerobic skin bacterium Cutibacterium acnes (formerly Propionibacterium acnes), sometimes found on culture during LDH surgery, has been suggested as a cause. Given worldwide concern over multidrug resistant bacteria, further investigation is highly warranted. Our study aimed to compare findings regarding bacterial presence in painful lumbar degenerative disc disease (DDD) in adults having LDH with findings in young patients with scoliosis, but without DDD or relevant lumbar pain. Methods: Between 2015 and 2017, 40 adults with LDH (median age 43, IQR 33-49) and 20 patients with scoliosis (median age 17, IQR 15-20) underwent surgery at seven Swedish hospitals. Samples were collected and cultured from skin, surgical wound, discs and vertebrae. Genetic relatedness of C. acnes isolates was investigated using single nucleotide polymorphism (SNP) analysis. DNA samples collected from discs/vertebrae were analysed using 16S rRNA-based PCR sequencing. Preoperative MRI findings were assessed for inflammatory Modic changes. Findings: No bacterial growth was found in 6/40 (15%) LDH patients, compared with 3/20 (15%) scoliosis patients. A single species, C. acnes, was found exclusively in the disc/vertebra from one patient in each group; in the LDH group, 29/40 (72%) patients had at least one sample with growth of C. acnes, while the corresponding figure in the scoliosis group was 14/20 (70%). There was no association between bacterial findings and Modic changes. Interpretations: The results suggest that finding bacteria like C. acnes in discs and vertebrae during surgery is likely due to contamination. Antibiotic use to treat LBP/LDH without signs of clinical discitis/spondylitis should be seriously questioned. Funding Statement: The study was funded by FORSS, a Swedish regional research foundation Declaration of Interests: The authors state: " no conflicts of interest to declare." Ethics Approval Statement: The study was approved by the ethical committee in Linkoping (EPN, Ref. no. 2015/152-31). All patients gave their written informed consent.

The number of patients infected with nontuberculous mycobacteria (NTM) is increasing and presents severe health problems. NTM infections in children are not uncommon and differ in several aspects from NTM infections in adults. In children, lymph nodes are most often infected, while lung infections dominate among adults. Thus, this chapter on NTM infections will focus on infections in children and pulmonary infections in adults. The reason why NTM diseases have been more commonly recognized is partly due to increased awareness and improved diagnostic methods. In addition, the number of patients with impaired resistance to infections has increased and such conditions are important risk factors for developing NTM disease. However, many NTM patients, particularly children, have no known predisposing condition. In addition, spontaneous resolution is common among children. Diagnosis and treatment are challenging since many patients suffer from other diseases and many NTM are resistant to commonly used drugs. Therapy is, therefore, generally complex and prolonged and side effects are common.

Purpose To compare bacterial findings in pain-generating degenerated discs in adults operated on for lumbar disc herniation (LDH), and mostly also suffering from low back pain (LBP), with findings in adolescent patients with non-degenerated non-pain-generating discs operated on for scoliosis, and to evaluate associations with Modic signs on magnetic resonance imaging (MRI). Cutibacterium acnes (Propionibacterium acnes) has been found in painful degenerated discs, why it has been suggested treating patients with LDH/LBP with antibiotics. As multidrug-resistant bacteria are a worldwide concern, new indications for using antibiotics should be based on solid scientific evidence. Methods Between 2015 and 2017, 40 adults with LDH/LBP (median age 43, IQR 33–49) and 20 control patients with scoliosis (median age 17, IQR 15–20) underwent surgery at seven Swedish hospitals. Samples were cultured from skin, surgical wound, discs and vertebrae. Genetic relatedness of C. acnes isolates was investigated using single-nucleotide polymorphism analysis. DNA samples collected from discs/vertebrae were analysed using 16S rRNA-based PCR sequencing. MRI findings were assessed for Modic changes. Results No bacterial growth was found in 6/40 (15%) LDH patients, compared with 3/20 (15%) scoliosis patients. Most positive samples in both groups were isolated from the skin and then from subcutis or deep within the wound. Of the four disc and vertebral samples from each of the 60 patients, 235/240 (98%) were DNA negative by bacterial PCR. A single species, C. acnes, was found exclusively in the disc/vertebra from one patient in each group. In the LDH group, 29/40 (72%) patients had at least one sample with growth of C. acnes, compared to 14/20 (70%) in the scoliosis group. Bacterial findings and Modic changes were not associated. Conclusions Cutibacterium acnes found in discs and vertebrae during surgery for disc herniation in adults with degenerated discs may be caused by contamination, as findings in this group were similar to findings in a control group of young patients with scoliosis and non-degenerated discs. Furthermore, such findings were almost always combined with bacterial findings on the skin and/or in the wound. There was no association between preoperative Modic changes and bacterial findings. Antibiotic treatment of lumbar disc herniation with sciatica and/or low back pain, without signs of clinical discitis/spondylitis, should be seriously questioned. Graphic abstract These slides can be retrieved under Electronic Supplementary Material.

Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the distribution differed depending on MIRU-VNTR limitations. Both genotyping techniques identified clusters where epidemiologic linking was insufficient, although WGS had higher correlation with epidemiologic data. To summarize, WGS provided better resolution of transmission than MIRU-VNTR in a setting with low TB incidence. WGS predicted epidemiologic links better which could consolidate and correct the epidemiologically linked cases, avoiding thus false clustering.

Global spread of aggressive mycobacteria Many mycobacteria, in addition to those causing leprosy and tuberculosis, are capable of infecting humans. Some can be particularly dangerous in patients suffering from immunosuppression or chronic disease, such as cystic fibrosis (CF). Bryant et al. observed clusters of near-identical isolates of drug-resistant Mycobacterium abscessus in patients reporting to CF clinics. The similarity of the isolates suggests transmission between patients, rather than environmental acquisition. Although this bacterium is renowned for its environmental resilience, the mechanism for its long-distance transmission among the global CF patient community remains a puzzle. Science , this issue p. 751

Unfortunately, the 5th author name was incorrectly published in the original paper. The complete correct name is given below.

Pepducins containing a fatty acid linked to an amino acid sequence derived from cytosolic parts of a G-protein-coupled receptor (GPCR) constitute a new group of lipopeptide tools in GPCR studies. Pepducins corresponding to the third intracellular loop of formyl peptide receptor 2 (FPR2) activate human neutrophils, and we show here that, in addition, these allosteric modulators of receptor activity also kill bacteria. The functional dualism of FPR2 pepducins could potentially be explored as a novel class of antibacterial drugs with immunomodulatory properties.

Interleukin-17 (IL-17) is produced by a subset of CD4(+) T helper (Th) lymphocytes known as Th17 cells. In humans, IL-1β, enhanced by IL-6 and IL-23 is crucial for differentiation of these cells. IL-17 evokes inflammation and is involved in host defence against microorganisms, although little is known about its role in diseases caused by non-tuberculous mycobacteria. The genus Mycobacterium contains both obligate and opportunistic pathogens as well as saprophytes, and the mycobacterial cell envelope is unique in its abundance of lipids. Here we investigated IL-17 and IL-23 production in human PBMC in response to intact UV-inactivated mycobacteria and mycobacterial surface lipids from two opportunistic (Mycobacterium avium and Mycobacterium abscessus) and one generally non-pathogenic (Mycobacterium gordonae) species. Representative Gram-positive (Enterococcus faecalis, Streptococcus mitis) and Gram-negative (Escherichia coli) bacteria were included as controls. Intact mycobacteria induced production of large amounts of IL-17, while IL-17 responses to control bacteria were negligible. Purified CD4(+) T cells, but not CD4-depleted cell fractions, produced this IL-17. Isolated mycobacterial surface lipids induced IL-17, but not IL-23 production. The ability of the non-tuberculous mycobacteria to induce IL-17 production in CD4(+) T cells was the same regardless of the pathogenic potential of the particular mycobacterial species.

Mycobacterium abscessus is a non-tuberculous mycobacteria able to cause opportunistic infections in selected patient groups. During the last decades it has emerged as a cause of chronic pulmonary infection in patients with cystic fibrosis (CF). M. abscessus strains exhibit either smooth or rough colony morphology. Strains exhibiting the rough phenotype more often cause pulmonary infections in CF patients than did the smooth ones. Here, we examined phagocytosis and production of cytokines by human peripheral blood mononuclear cells, in response to M. abscessus strains with smooth and rough colony phenotype. The rough isolates all formed multicellular cords, similar to what is observed in Mycobacterium tuberculosis. Monocytes were generally unable to internalize these rough cord isolates, in contrast with the smooth ones. Furthermore, the rough M. abscessus strains induced a distinct cytokine profile differing from that induced by the smooth ones. Rough isolates induced significantly less IL-10 and tumour necrosis factor compared to smooth strains, but more IL-1β. Both varieties induced equal amounts of IFN-γ, IL-17, IL-23, IL-6, IL-8 and equally little IL-12. The ability to withstand phagocytosis might be a virulence factor contributing to the capacity of rough M. abscessus strains to give persistent pulmonary infections.

The black-pigmented fungus Exophiala dermatitidis is considered to be a harmless colonizer of the airways of cystic fibrosis (CF) patients. The aim of this study was to establish the recovery rate of E. dermatitidis in respiratory specimens from CF patients, transplant recipients, and subjects with other respiratory disorders in Sweden. Second, we wished to determine if particular clinical traits were associated with E. dermatitidis colonization of the airways and the antifungal susceptibility profiles of Exophiala strains. Sputum and bronchoalveolar lavage samples ( n = 492) derived from 275 patients were investigated. E. dermatitidis was isolated in respiratory specimens from 19% (18/97) of the CF patients but in none of the other patient categories. All isolates were recovered after 6 to 25 days of incubation on erythritol-chloramphenicol agar (ECA) medium. Morphological and genetic analyses confirmed species identity. Pancreatic insufficiency was positively associated with the presence of E. dermatitidis in sputum samples ( P = 0.0198). Antifungal susceptibility tests demonstrated that voriconazole and posaconazole had the lowest MICs against E. dermatitidis . In conclusion, E. dermatitidis is a frequent colonizer of the respiratory tract in CF patients in Sweden and appears to be associated with more advanced disease. Whether E. dermatitidis is pathogenic remains to be elucidated.

For some forty years the eye-tracking technology has facilitated the study of eye movement patterns for sighted people during reading and other visual activities. Today - a newly developed automati ...

Instead of discussing existing design methods that aim at bridging or annihilating gaps between users and designers, we want to highlight an approach for designers that helps us increase reflexivit ...

The Cobas TaqMan MTB assay is used for rapid detection of the Mycobacterium tuberculosis complex (MTC) in clinical samples. It is only validated for respiratory samples, but is often requested by physicians for non-respiratory specimens. The aim of this study was therefore to evaluate the performance of this assay in clinical praxis in a country with low prevalence of tuberculosis (TB).The results from 2388 respiratory and 1005 non-respiratory human specimens were analyzed by this real-time PCR technique. Using culture results as the gold standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) of the PCR results were calculated.For smear-positive respiratory specimens all the four values investigated were 100%. The number of smear-positive non-respiratory specimens was only eight, and all of these eight specimens reacted positively. Sensitivity was 51% for smear-negative respiratory specimens, and 47% for smear-negative non-respiratory specimens. When all non-respiratory specimens were analyzed together the sensitivity was 51%. Specimens from 16 patients were PCR-positive but culture-negative and these cases are discussed. In one case, TB DNA was still present in sputum 2 years after a successful treatment.The study shows that the Cobas TaqMan MTB assay performs well in smear-positive samples, while the sensitivities are unsatisfactory for both respiratory and non-respiratory smear-negative specimens. Furthermore, the analyses emphasize that this assay cannot be used to evaluate treatment or contagiousness, or to detect relapses or screen for TB.

The pilot project reported here utilized the first technology ever developed for the computerized on-line registration and analysis of finger movements during Braille reading. Five congenitally blind subjects performed tactile reading of pedagogically carefully selected texts. Two specialists in visual impairments analyzed the computer-registered reading activities using specially designed interaction software. The subjects themselves were interviewed and contributed to discussions about their own individual reading styles. The analyses of this first handful of subjects reveal a number of important strategies and preferences with regard to on-line tactile reading. Further, the results challenge several assumptions and practices in Braille teaching. This pilot project lays the foundation for more comprehensive large-scale studies—both cross-sectional and longitudinal ones—studies long wanted in the domain of tactile reading.

BACKGROUND: Pyrazinamide (PZA) is a key drug in the treatment of tuberculosis (TB), including multidrug-resistant TB. Drug susceptibility testing (DST) of Mycobacterium tuberculosis against PZA is not included in the World Health Organization's yearly proficiency testing. There is an increasing need to establish quality control of PZA DST. OBJECTIVE: To evaluate the performance of PZA DST and to introduce a quality assurance system for the test in Sweden. METHOD: Panels with PZA-susceptible and -resistant isolates were used in three rounds of proficiency testing in all five Swedish clinical TB laboratories and our reference laboratory. All laboratories used the MGIT 960 system. Minimum inhibitory concentrations (MICs) were determined and the pncA gene was sequenced to further characterise the 52 panel strains. RESULTS: Good agreement was seen between the phenotypic PZA DST and pncA sequence data, and MIC determination confirmed high levels of resistance. However, in contrast to other drugs, for which correct proficiency test results were observed, specificity problems occurred for PZA DST in some laboratories. CONCLUSIONS: In Sweden, using panel testing, differences were seen in the proficiency of TB laboratories in correctly identifying PZA susceptibility. Improved results were noted in the third round; PZA has therefore been included in yearly proficiency testing.

Mononuclear phagocytes, that is, monocytes and macrophages, are central in the defense against mycobacteria. Mycobacterium abscessu s is an opportunistic mycobacterial species able to cause chronic pulmonary infections in patients with cystic fibrosis but also soft tissue infections in immunocompetent individuals. Pathogenic isolates of M. abscessus with rough colony morphology form cord-like aggregates. In this study, we investigated the in vitro response of human peripheral blood mononuclear cells (PBMCs) from healthy blood donors to cord-forming M. abscessus strains from cystic fibrosis patients with clinical lung infection. Microscopic examination revealed that the PBMCs produced a coarse fibrous meshwork containing DNA and histones, which surrounded the mycobacterial cords. Thus, the bacterial cord formations were entrapped by monocytes and lymphocytes aggregated onto the DNA-rich meshwork fibers. Mycobacterium abscessus strains with smooth colony morphology, which do not form cords and are readily phagocytosed, did not induce any meshwork formation in PBMCs. The chromatin meshwork may represent a defense mechanism against nondigestible invaders.

An online survey in the form of a questionnaire was conducted to obtain the opinion of computer users with tetraplegia on their current computer interfaces and to assess desirable applications for future independent control using assistive devices. The survey included questions related to information about the respondents' injury/disease, everyday activities and social life, electronic devices and computer programs, evaluation of computer interfaces, and desirable applications for assistive devices. The survey was distributed via tetraplegia associations, magazines, and Internet forums mainly in Denmark and Sweden, but also through other European and American associations. Thirty-one completed questionnaires were collected from individuals with spinal cord injury and other neuromuscular diseases that resulted in tetraplegia. Respondents evaluated gaze and head trackers; speech recognition systems; chin, mouth, and hand joysticks; sip and puff interfaces; and typing sticks. Most interfaces were evaluated i...

BACKGROUND: Mycobacterium avium is the principal etiologic agent of non-tuberculous lymphadenitis in children. It is also a known pathogen for birds and other animals. Genetic typing of M. avium isolates has led to a proposal to expand the set of subspecies to include M. avium subsp. hominissuis. Isolates associated with disease in humans belong to this subspecies. METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood mononuclear cells from six healthy blood donors were stimulated in vitro with ten isolates of M. avium avium and 11 isolates of M. avium hominissuis followed by multiplex bead array quantification of cytokines in supernatants. M. avium hominissuis isolates induced significantly more IL-10 and significantly less IL-12p70, TNF, IFN-γ and IL-17 when compared to M. avium avium isolates. All strains induced high levels of IL-17, but had very low levels of IL-12p70. CONCLUSION/SIGNIFICANCE: The strong association between M. avium subsp. hominissuis and disease in humans and the clear differences in the human immune response to M. avium subsp. hominissuis compared to M. avium subsp. avium isolates, as demonstrated in this study, suggest that genetic differences between M. avium isolates play an important role in the pathogenicity in humans.

The genus Mycobacterium includes obligate pathogens as well as opportunistic and non-pathogenic species ubiquitous in the environment. Mycobacteria have a unique cell wall abundant in lipids. Here we investigated cytokine production by human peripheral blood mononuclear cells (PBMC) in response to the opportunistic mycobacteria Mycobacterium avium and Mycobacterium abscessus, the non-pathogenic Mycobacterium gordonae and extracted surface lipids from the three species. The cytokine response elicited by mycobacteria, regardless of their pathogenic potential, differed distinctly from that induced by control Gram-positive (Enterococcus faecalis, Streptococcus mitis) and Gram-negative (Escherichia coli) bacteria. Mycobacteria induced no IL-12 and less TNF and IFN-γ compared with conventional Gram-positive bacteria. IL-10 was induced by all the mycobacteria and this production was partly responsible for the down-regulation of IL-12 and IFN-γ. The capacity of the Gram-positive bacterium E. faecalis to induce IL-12, as well as TNF and IFN-γ, in human PBMCs was strongly reduced when mycobacterial lipids were added. The mycobacterial surface lipids down-regulated the production of IL-12 and IFN-γ without eliciting IL-10 production. Our results show that mycobacteria evade triggering production of phagocyte activating cytokines (IL-12, TNF and IFN-γ) and that the mycobacterial cell wall surface lipids may play a significant role in this process.

Background In the tsunami catastrophe in Thailand in 2004, several thousand Swedish tourists were injured, with contaminated crush trauma of the legs being the main cause of injury among the survivors. Methods Patient and laboratory data for those who received hospital care in Stockholm and Gothenburg and contracted late-onset infections due to rapid-growing mycobacteria were reviewed retrospectively. Also, concomitant infections were recorded. Results Fifteen patients with late-onset skin and soft-tissue infections due to rapid-growing mycobacteria are described here. Mycobacterium abscessus was isolated in 7 cases, Mycobacterium fortuitum was isolated in 6 cases, and Mycobacterium peregrinum and Mycobacterium mageritense were isolated in 1 case each. The infections appeared after a delay of 20-105 days (median, 60 days) after the trauma, targeting undamaged skin located near primary sutured wounds or skin grafts. Antimycobacterial drugs were given to 9 (60%) of the patients. The course of infection was protracted, but all infections due to rapid-growing mycobacteria healed within 12 months. Concomitant subcutaneous infections due to other microorganisms, such as Burkholderia pseudomallei or Cladophialophora bantiana, appeared early or late after the trauma. Conclusions Repeated cultures of abscess and wound specimens for Mycobacterium species may be needed to find the etiologic agents causing contaminated skin and soft-tissue infections, such as those that developed after traumas that occurred during the tsunami. These cultures are especially necessary when symptoms appear late and when conventional bacterial culture results are negative. A biopsy is recommended for the best yield and for complementary histopathological examination.

Instead of discussing existing design methods that aim at bridging or annihilating gaps between users and designers, we want to highlight an approach for designers that helps us increase reflexivity of what is beyond our grasp when interacting with users. The first steps are to become aware of the gaps, identify them, and then manage them. This emphasises and makes visible to both parties the existing differences in conceptions. The tension between these differences is considered to be the potential for mutual learning which benefits future design processes involving the same communities of practice. This will be exemplified by four cases relevant for designers and implemented in the area of ageing and design.

This paper presents a person-centred model and a tangible computing approach to better adapt television media to meet two important needs of older people: social inclusion in their immediate surrou ...

Mycobacterium abscessushas been isolated increasingly often from the respiratory tracts of cystic fibrosis (CF) patients. It is not known whether these organisms are transmitted from person to person or acquired from environmental sources. Here, colony morphology and pulsed-field gel electrophoresis (PFGE) pattern were examined for 71 isolates ofM. abscessusderived from 14 CF patients, three non-CF patients with chronic respiratoryM. abscessusinfection or colonization, one patient with mastoiditis, and four patients with infected wounds, as well as for six isolates identified as environmental contaminants in various clinical specimens. Contaminants and wound isolates mainly exhibited smooth colony morphology, while a rough colony phenotype was significantly associated with chronic airway colonization (P= 0.014). Rough strains may exhibit increased airway-colonizing capacity, the cause of which remains to be determined. Examination by PFGE of consecutive isolates from the same patient showed that they all represented a single strain, even in cases where both smooth and rough isolates were present. When PFGE patterns were compared, it was shown that 24 patients had unique strains, while four patients harbored strains indistinguishable by PFGE. Two of these were siblings with CF. The other two patients, one of whom had CF, had not had contact with each other or with the siblings. Our results show that most patients colonized byM. abscessusin the airways have unique strains, indicating that these strains derive from the environment and that patient-to-patient transmission rarely occurs.

(2005). Communication aids for people with aphasia. Logopedics Phoniatrics Vocology: Vol. 30, No. 1, pp. 41-46.

Applied ethics in research is no longer regarded as a concern exclusive to the medical field. Exemplars in ethics from other fields such as design are, however, meagre, as are relevant practical and design applied guidelines. The more ethically grounded a given area of research is, the greater the chance it can contribute to long-term, meaningful breakthroughs in knowledge. An improved ethics in design can enable a critical questioning that in turn leads to entirely new research questions. The mere involvement of human subjects and the application of safety provisions in design research do not guarantee it will meet ethical considerations, best practices or standards. The entire complex interaction with users offers intriguing possibilities and risks, or can result in mediocrity in areas such as: preparation and implementation that is worth the research person’s time; respect for users’ contributions; dignified treatment; feedback in an iterative and interactive process with mutual information and inspiration; and products and processes that are truly influenced by the users. This reasoning applies to all, but with special distinction to people who are disabled and elderly. Starting with specific needs as opposed to more general ones (the latter of which result in the necessity for more abstract specifications for the multitudes) can, above and beyond the ethical dimension, also result in increased innovation and effectiveness for society on the whole. Proceeding from the particular to the general is of considerable value, for ethical reasons as well as for sheer effectiveness. Involving persons with a variety of disabilities in product development helps to ensure innovative and useworthy products.[1] One of many prerequisites for ethically sound user involvement is that all participants are aware of the interference taking place in an iterative design process. An elaboration of ethical aspects in design can be valuable for different stakeholders (user organisations, NGOs and the design community) and, of course, for the relevance of resulting products and processes. A more considerate ethical approach could have substantial economical value due to the higher relevance of the results. There has been a considerable increase in the ethical expectations placed on businesses and professions in recent years. Scores of organisations have reacted by developing ethical codes of conduct and professional guidelines to explicitly state their values and principles.[2] Moreover, the drafting of a code of ethics can be seen as an indication of professionalism in an emerging profession.[3]

The genetic diversity of Mycobacterium tuberculosis isolates among patients from Sweden was determined by a combination of two PCR-based techniques (spoligotyping and variable number of tandem repeats analysis). It resulted in a clustering of 23.6% of the isolates and a rate of recent transmission of 14.1%. The clustered isolates mainly belonged to the Haarlem family (23.2%), followed by the Beijing (9.8%), Latin American and Mediterranean (LAM; 8%), and East African-Indian (EAI; 6.2%) families. A comparison of the spoligotypes with those in the international spoligotyping database showed that 62.5% of the clustered isolates and 36.6% of all isolates typed were grouped into six major shared types. A comparison of the spoligotypes with those in databases for Scandinavian countries showed that 33% of the isolates belonged to an ill-defined T family, followed by the EAI (22%), Haarlem (20%), LAM (11%), Central Asian (5%), X (5%), and Beijing (4%) families. Both the highest number of cases and the proportion of clustered cases were observed in patients ages 15 to 39 years. Nearly 10% of the isolates were resistant to one or more drugs (essentially limited to isoniazid monoresistance). However, none of the strains were multidrug resistant. Data on the geographic origins of the patients showed that more than two-thirds of the clustered patients with tuberculosis were foreign-born individuals or refugees. These results are explained on the basis of both the historical links within specific countries and recently imported cases of tuberculosis into Sweden.

A developmental disability often includes a language disorder, the result of which render learning, in part, if not entirely impossible. This has drastic consequences for children and adults, and gradually ends up becoming the primary disability. With to

The Cobas Amplicor MTB test is a polymerase chain reaction (PCR) technique commonly used for direct detection of Mycobacterium tuberculosis in clinical samples. This assay is only validated for respiratory specimens, but many physicians also request PCR analyses for non-respiratory ones. 877 respiratory and 564 non-respiratory specimens were analysed by this test. Using culture results as standard, the sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the PCR were, respectively, 97.9%, 100%, 100% and 94.4% for smear-positive respiratory specimens, 68.8%, 99.2%, 87.5% and 97.5% for smear-negative respiratory samples, 57.8%, 98.6%, 78.8% and 96.4% for all non-respiratory specimens, and 42.4%, 98.6%, 66.7% and 96.4% for smear-negative non-respiratory specimens. 154 cerebrospinal fluid samples were analysed and the sensitivity, specificity, PPV and NPV were 55.6%, 97.2%, 55.6% and 97.2%, respectively. These results indicate that the Cobas Amplicor MTB test enables detection of tuberculosis in respiratory specimens, but does not perform well enough in non-respiratory specimens. The method fails particularly in cases where a reliable and rapid test is urgently needed, e.g. in tuberculous meningitis.

Background: The metallation of closed ring tetrapyrroles resulting in the formation of hemes, chlorophylls and vitamin B 12 is catalyzed by specific enzymes called chelatases. Ferrochelatase catalyzes the terminal step in heme biosynthesis by inserting ferrous ion into protoporphyrin IX by a mechanism that is poorly understood. Mutations in the human gene for ferrochelatase can result in the disease erythropoietic protoporphyria, and a further understanding of the mechanism of this enzyme is therefore of clinical interest. No three-dimensional structure of a tetrapyrrole metallation enzyme has been available until now. Results: The three-dimensional structure of Bacillus subtilis ferrochelatase has been determined at 1.9 A resolution by the method of multiple isomorphous replacement. The structural model contains 308 of the 310 amino acid residues of the protein and 198 solvent molecules. The polypeptide is folded into two similar domains each with a four-stranded parallel β sheet flanked by α helices. Structural elements from both domains build up a cleft, which contains several amino acid residues that are invariant in ferrochelatases from different organisms. In crystals soaked with gold and cadmium salt solutions, the metal ion was found to be coordinated to the conserved residue His 183, which is located in the cleft. This histidine residue has previously been suggested to be involved in ferrous ion binding. Conclusions: Ferrochelatase seems to have a structurally conserved core region that is common to the enzyme from bacteria, plants and mammals. We propose that porphyrin binds in the identified cleft; this cleft also includes the metal-binding site of the enzyme. It is likely that the structure of the cleft region will have different conformations upon substrate binding and release.

Discrete γ-ray lines emitted after (n,2n) and (n,n') reactions in radiogenic and natural lead at 15.5 MeV neutron energy have been studied. Differential 120° cross sections have been determined relative to the cross section for the ground state transition from the 4.44 MeV level of 12C populated through inelastic scattering. The (n,2n) and (n,n') contributions to the cross sections for the most dominant γ-ray lines in 206Pb and 207Pb have been separated. Upper and lower limits of the cross sections for (n,2n) and (n,n') reactions in lead are estimated. The results indicate that the statistical theory of nuclear reactions fails to give a correct description of neutron emission processes in lead at 15 MeV neutron energy.