Mycobacterium canettii, the smooth variant of M. tuberculosis, isolated from a Swiss patient exposed in Africa.

An exceptionally smooth and glossy morphotype of Mycobacterium tuberculosis complex was isolated from a 56-year-old Swiss patient with mesenteric tuberculosis. Direct 16S rRNA sequence analysis of the hypervariable signature gene regions revealed a 100% homology to the specific M. tuberculosis complex sequence. Spoligotyping and restriction fragment length polymorphism analyses using the insertion sequences IS6110 and IS1081 and the polymorphic GC-rich sequence as additional genetic markers identified the isolate as the novel taxon M. canettii. Like a Somali child with a similar case, this patient probably contracted the infection in Africa, which raises questions about the geographic distribution of M. canettii

Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance.

BACKGROUND: Data on the performance of standardized short-course directly observed treatment (DOTS) of tuberculosis (TB) in areas with high levels of drug resistance and on the potential impact of DOTS on amplification of resistance are limited. Therefore, we analyzed treatment results from a cross-sectional sample of patients with TB enrolled in a DOTS program in an area with high levels of drug resistance in Uzbekistan and Turkmenistan in Central Asia. METHODS: Sputum samples for testing for susceptibility to 5 first-line drugs and for molecular typing were obtained from patients starting treatment in 8 districts. Patients with sputum smear results positive for TB at the end of the intensive phase of treatment and/or at 2 months into the continuation phase were tested again. RESULTS. Among 382 patients with diagnoses of TB, 62 did not respond well to treatment and were found to be infected with an identical Mycobacterium tuberculosis strain when tested again; 19 of these patients had strains that developed new or additional drug resistance. Amplification occurred in only 1.2% of patients with initially susceptible or monoresistant TB strains, but it occurred in 17% of those with polyresistant strains (but not multidrug-resistant strains, defined as strains with resistance to at least isoniazid and rifampicin) and in 7% of those with multidrug-resistant strains at diagnosis. Overall, 3.5% of the patients not initially infected with multidrug-resistant TB strains developed such strains during treatment. Amplification of resistance, however, was found only in polyresistant Beijing genotype strains. CONCLUSIONS: High levels of amplification of drug resistance demonstrated under well-established DOTS program conditions reinforce the need for implementation of DOTS-Plus for multidrug-resistant TB in areas with high levels of drug resistance. The strong association of Beijing genotype and amplification in situations of preexisting resistance is striking and may underlie the strong association between this genotype and drug resistance

Multidrug-resistant tuberculosis in prison inmates, Azerbaijan.

In a tuberculosis (TB) program in the Central Penitentiary Hospital of Azerbaijan, we analyzed 65 isolates of Mycobacterium tuberculosis by IS6110-based restriction fragment-length polymorphism (RFLP) and spoligotyping. From 11 clusters associated with 33 patients, 31 isolates had an IS6110-based banding pattern characteristic of the Beijing genotype of M. tuberculosis. In addition, 15 M. tuberculosis isolates with similar RFLP patterns constituted a single group by spoligotyping, matching the Beijing genotype. Multidrug resistance, always involving isoniazid and rifampin, was seen in 34 (52.3%) of 65 isolates, with 28 belonging to the Beijing genotype

CRISPRcompar: a website to compare clustered regularly interspaced short palindromic repeats

Clustered regularly interspaced short palindromic repeat (CRISPR) elements are a particular family of tandem repeats present in prokaryotic genomes, in almost all archaea and in about half of bacteria, and which participate in a mechanism of acquired resistance against phages. They consist in a succession of direct repeats (DR) of 24–47 bp separated by similar sized unique sequences (spacers). In the large majority of cases, the direct repeats are highly conserved, while the number and nature of the spacers are often quite diverse, even among strains of a same species. Furthermore, the acquisition of new units (DR + spacer) was shown to happen almost exclusively on one side of the locus. Therefore, the CRISPR presents an interesting genetic marker for comparative and evolutionary analysis of closely related bacterial strains. CRISPRcompar is a web service created to assist biologists in the CRISPR typing process. Two tools facilitates the in silico investigation: CRISPRcomparison and CRISPRtionary. This website is freely accessible at http://crispr.u-psud.fr/CRISPRcompar/

Long-term musculoskeletal function after Open Pelvic ring fractures in Children (OPEC); a multicentre, retrospective case series with follow-up measurement

Background: The proportion of Open Pelvic fractures in the paediatric population is relatively high. While operative fixation is the primary approach for managing Open Pelvic fractures in adults, there is limited literature on treatment outcomes in Children, particularly regarding long-term musculoskeletal, neurological, and urogenital function. Methods: This multicentre case series included paediatric patients (&lt;18 years old) with Open Pelvic ring fractures treated at one of two major trauma centres in the Netherlands between January 1, 2001 and December 31, 2021. Data collection involved clinical records and long-term assessments, including musculoskeletal function, growth disorders, urogenital function, sexual dysfunction, and sensory motor function. Results: A total of 11 patients were included, primarily females (73 %), with a median age at trauma of 12 years (P25–P75 7–14). Most patients had unstable Pelvic ring fractures resulting from high-energy trauma. Surgical interventions were common, with external fixation as the main initial surgical approach (n = 7, 70 %). Complications were observed in eight (73 %) patients. Musculoskeletal function revealed a range of issues in the lower extremity, daily activities, and mental and emotional domain. Long-term radiologic follow-up showed high rates of Pelvic malunion (n = 7, 64 %). Neurological function assessment showed motor and sensory function impairment in a subset of patients. Urogenital function was moderately affected, and sexual dysfunction was limited with most respondents reporting no issues. Conclusion: Paediatric Open Pelvic fractures are challenging injuries associated with significant short-term complications and long-term musculoskeletal and urogenital issues. Further research is needed to develop tailored treatment strategies and improve outcomes of these patients.</p

Effects of direct renin blockade on renal & systemic hemodynamics and on raas activity, in weight excess and hypertension: A randomized clinical trial

Aim: The combination of weight excess and hypertension significantly contributes to cardiovascular risk and progressive kidney damage. An unfavorable renal hemodynamic profile is thought to contribute to this increased risk and may be ameliorated by direct renin inhibition (DRI). The aim of this trial was to assess the effect of DRI on renal and systemic hemodynamics and on RAAS activity, in men with weight excess and hypertension. Methods: A randomized, double-blind, cross-over clinical trial to determine the effect of DRI (aliskiren 300 mg/day), with angiotensin converting enzyme inhibition (ACEi; ramipril 10 mg/day) as a positive control, on renal and systemic hemodynamics, and on RAAS activity (n = 15). Results: Mean (SEM) Glomerular filtration rate (101 (5) mL/min/1.73m2) remained unaffected by DRI or ACEi. Effective renal plasma flow (ERPF; 301 (14) mL/min/1.73m2) was increased in response to DRI (320 (14) mL/min/1.73m2, P = 0.012) and ACEi (317 (15) mL/min/1.73m2, P = 0.045). Filtration fraction (FF; 34 (0.8)%) was reduced by DRI only (32 (0.7)%, P = 0.044). Mean arterial pressure (109 (2) mmHg) was reduced by DRI (101 (2) mmHg, P = 0.008) and ACEi (103 (3) mmHg, P = 0.037). RAAS activity was reduced by DRI and ACEi. Albuminuria (20 [9±42] mg/d) was reduced by DRI only (12 [5±28] mg/d, P = 0.030). Conclusions: In men with weight excess and hypertension, DRI and ACEi improved renal and systemic hemodynamics. Both DRI and ACEi reduced RAAS activity. Thus, DRI provides effective treatment in weight excess and hypertension

A Geographically-Restricted but Prevalent Mycobacterium tuberculosis Strain Identified in the West Midlands Region of the UK between 1995 and 2008

Background: We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK.Methodology/Principal Findings: Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the "Mercian" strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95% CI = 4.56-17.87, p 65 years old (OR = 0.25, 95% CI = 0.09-0.67, p < 0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95% CI = 2.00-46.78, p < 0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95% CI = 1.45-27.02, p = .01) were observed as social risk factors for infection.Conclusions/Significance: The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain

Mycobacterium tuberculosis Transmission from Human to Canine

A 71-year-old woman from Tennessee, USA with a 3-week history of a productive, nonbloody cough was evaluated. Chest radiograph showed infiltrates and atelectasis in the upper lobe of the right lung. A tuberculosis (TB) skin test resulted in a 14-mm area of induration. Sputum stained positive for acid-fast bacilli (AFB) and was positive for Mycobacterium tuberculosis by DNA probe and culture. Treatment was initiated with isoniazid, rifampicin, and pyrazinamide. After 14 days of daily, directly observed therapy, the patient complained of nausea, vomiting and diarrhoea. Treatment adjustments were made, and therapy was completed 11 months later with complete recovery. Six months after the patient\u27s TB diagnosis, she took her three and a half-year-old male Yorkshire Terrier to a veterinary clinic with cough, weight loss, and vomiting of several months\u27 duration. Initial sputum sample was negative on AFB staining. Eight days after discharge from a referral veterinary teaching hospital with a presumptive diagnosis of TB, the dog was euthanized due to urethral obstruction. Liver and tracheobronchial lymph node specimens collected at necropsy were positive for M. tuberculosis complex by polymerase chain reaction. The M. tuberculosis isolates from the dog and its owner had an indistinguishable 10-band pattern by IS6110-based restriction fragment length polymorphism genotyping

Structural and mechanistic insights into a Bacteroides vulgatus retaining N-acetyl-β-galactosaminidase that uses neighbouring group participation

Bacteroides vulgatus is a member of the human microbiota whose abundance is increased in patients with Crohn's disease. We show that a B. vulgatus glycoside hydrolase from the carbohydrate active enzyme family GH123, BvGH123, is an N-acetyl-β-galactosaminidase that acts with retention of stereochemistry, and, through a 3-D structure in complex with Gal-thiazoline, provide evidence in support of a neighbouring group participation mechanism