23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A-->G

The 23S rRNA A2058G alteration mediates macrolide, lincosamide, and streptogramin B resistance in the bacterial domain and determines the selectivity of macrolide antibiotics for eubacterial ribosomes, as opposed to eukaryotic ribosomes. However, this mutation is associated with a disparate resistance phenotype: It confers high-level resistance to ketolides in mycobacteria but only marginally affects ketolide susceptibility in streptococci. We used site-directed mutagenesis of nucleotides within domain V of 23S rRNA to study the molecular basis for this disparity. We show that mutational alteration of the polymorphic 2057-2611 base pair from A-U to G-C in isogenic mutants of Mycobacterium smegmatis significantly affects susceptibility to ketolides but does not influence susceptibility to other macrolide antibiotics. In addition, we provide evidence that the 2057-2611 polymorphism determines the fitness cost of the 23S rRNA A2058G resistance mutation. Supported by structural analysis, our results indicate that polymorphic nucleotides mediate the disparate phenotype of genotypically identical resistance mutations and provide an explanation for the large species differences in the epidemiology of defined drug resistance mutations.     

Effects of some chemical and physical agents on the metacestode Taenia solium in spicy meat and sausage

OBJECTIVE: To assess the effect of different cooking times and temperatures, as well as of some seasonings, on the viability of Taenia solium metacestodes in spicy meat and hot sausage. MATERIAL AND METHODS: This study was conducted by the Universidad Autónoma de Guerrero (Guerrero State Autonomous University), Mexico in 1999. Infected pork meat was bought in the community of Azacoaloya, in the municipality of Chilapa de Alvarez, Guerrero State. It was used to prepare spicy meat (adobada) and hot sausage (chorizo). Only the meat in which metacestode viability was proven was used. The products obtained underwent a) room temperature for 12 to 100 hours; b) temperatures of -10 to 37 degrees C for 24 hours; c) boiling (97 degrees C) from 1 to 15 minutes. To determine the effect of the seasonings, batches were prepared using twice the amount of a specific seasoning. Trials were done and assessed three times. Proportion differences were established using the chi-squared test. RESULTS: At room temperature the lowest evagination occurred after 100 hours for both products (p<0.05). After 24 hours, the lowest evagination occurred at -10 degrees C in spicy meat and at 37 degrees C in hot sausage (p<0.05). At boiling temperature there was no evagination after 10 minutes (p<0.05). In spicy meat, adding salt caused the most significant reduction; in hot sausage, thyme caused the most significant reduction (p<0.05). CONCLUSIONS: Meat with metacestodes should not be eaten, yet, it is being sold and used to prepare spicy meats. Adding spices can hide the metacestode, thus, adequate cooking of these meat products is necessary. These meats may be consumed at least four days after its preparation and spicy meat after a minimum of four days of refrigeration. The English version of this paper is available at: http://www.insp.mx/salud/index.html.     

Sinn und Unsinn von Antitussiva

· keine oder nur wenige objektivierbare quantitative klinische Parameter zur Verfügung stehen,     

Sinn und Unsinn von Antitussiva

Der breiten Anwendung von Hustentherapeutika steht eine unzureichende und meist kontroverse Studienlage gegenüber. Die Bewertung dieser Substanzen ist unter anderem deshalb problematisch, da · keine oder nur wenige objektivierbare quantitative klinische Parameter zur Verfügung stehen, · die antitussive Wirkung oft schwach ist oder · nur bestimmte Patientengruppen davon einen Nutzen zu haben scheinen. Die Fülle pflanzlicher und hom?opathischer Therapeutika unterschiedlichster Anwendungsformen tr?gt zu einer weiteren Verunsicherung bei, da es kontrollierte Studien mit diesen Substanzen meist nicht gibt. Oft fordern aber die Patienten, ungeachtet des fehlenden klinisch objektivierbaren Effektivit?tsnachweises, hustenblockierende oder die Expektoration f?rdernde Medikamente, sei es, weil ihr Leidensdruck hoch ist oder weil sie subjektiv eine Verbesserung verspüren. Diese übersicht gibt anhand der Literatur der letzten 20 Jahre einen überblick, wann der klinische Einsatz von Hustentherapeutika sinnvoll erscheint und wann nicht.     

Tabakrauchen und Lungenerkrankungen

Chronic cigarette smoking is the leading cause of preventable death and primarily affects the airways and lung parenchyma. It is a well-established prime risk factor for the development of chronic obstructive pulmonary disease (COPD) and lung cancer. Chronic cigarette smoking exacerbates pre-existing diseases of the airways and the lung parenchyma such as asthma and various forms of interstitial lung diseases. Additional exposure, e.g. in an occupational setting to asbestos fibres or silica, may act synergistically to increase the risk of lung cancer and pulmonary fibrosis and also of COPD. This paper gives a synopsis of smoking-induced pulmonary diseases with respect to epidemiology and pathology and how cigarette smoking affects the prognosis.     

Validation of the NAFLD fibrosis score in a Chinese population with low prevalence of advanced fibrosis

OBJECTIVES:  Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide. This study aimed to validate the NAFLD fibrosis score in the Chinese population.
METHODS:  NAFLD patients were prospectively recruited for liver biopsy and blood tests. The NAFLD fibrosis score was calculated as −1.675 + 0.037 × age (yr) + 0.094 × BMI (kg/m²) + 1.13 × impaired fasting glucose/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio–0.013 × platelet (×10⁹/L)−0.66 × albumin (g/dL). Advanced fibrosis was defined as stage 3 to 4 fibrosis.
RESULTS:  One hundred sixty-two patients (age 46 ± 10 yr, male 59%) were included in the study. Advanced fibrosis was found in 18 (11%) patients. Only 11 of 128 patients with the NAFLD fibrosis score below the proposed low cutoff point (<−1.455) were under-staged, resulting in a high negative predictive value of 91%. Only two patients exceeded the proposed high cutoff point (>0.676), but neither had advanced fibrosis. If the NAFLD fibrosis score was implemented in the Chinese population, 79% of liver biopsies could be avoided.
CONCLUSIONS:  The NAFLD fibrosis score has high negative predictive value in excluding advanced fibrosis in the Chinese population, and can reduce the burden of liver biopsy in the vast majority of cases. Since there were few cases of advanced fibrosis in this cohort, this study had limited power in validating the high cutoff point.     

Psychometric properties of the Zephyr bioharness device: a systematic review

Background

Technological development and improvements in Wearable Physiological Monitoring devices, have facilitated the wireless and continuous field-based monitoring/capturing of physiologic measures in healthy, clinical or athletic populations. These devices have many applications for prevention and rehabilitation of musculoskeletal disorders, assuming reliable and valid data is collected. The purpose of this study was to appraise the quality and synthesize findings from published studies on psychometric properties of heart rate measurements taken with the Zephyr Bioharness device.

Methods

We searched the Embase, Medline, PsycInfo, PuMed and Google Scholar databases to identify articles. Articles were appraised for quality using a structured clinical measurement specific appraisal tool. Two raters evaluated the quality and conducted data extraction. We extracted data on the reliability (intra-class correlation coefficients and standard error of measurement) and validity measures (Pearson/Spearman’s correlation coefficients) along with mean differences. Agreement parameters were summarised by the average biases and 95% limits of agreement.

Results

A total of ten studies were included: quality ratings ranged from 54 to 92%. The intra-class correlation coefficients reported ranged from 0.85–0.98. The construct validity coefficients compared against gold standard calibrations or other commercially used devices, ranged from 0.74–0.99 and 0.67–0.98 respectively. Zephyr Bioharness agreement error ranged from ??4.81 (under-estimation) to 3.00 (over-estimation) beats per minute, with varying 95% limits of agreement, when compared with gold standard measures.

Conclusion

Good to excellent quality evidence from ten studies suggested that the Zephyr Bioharness device can provide reliable and valid measurements of heart rate across multiple contexts, and that it displayed good agreements vs. gold standard comparators – supporting criterion validity.

     

The Tougher the Better: An Economic Analysis of Increased Payment Thresholds on the Performance of General Practices

We investigate whether and how a change in performance‐related payment motivated General Practitioners (GPs) in Scotland. We evaluate the effect of increases in the performance thresholds required for maximum payment under the Quality and Outcomes Framework in April 2006. A difference‐in‐differences estimator with fixed effects was employed to examine the number of patients treated under clinical indicators whose payment schedules were revised and to compare these with the figures for those indicators whose schedules remained unchanged. The results suggest that the increase in the maximum performance thresholds increased GPs' performance by 1.77% on average. Low‐performing GPs improved significantly more (13.22%) than their high‐performing counterparts (0.24%). Changes to maximum performance thresholds are differentially effective in incentivising GPs and could be used further to raise GPs' performance across all indicators. Copyright © 2013 John Wiley & Sons, Ltd.