Novel compounds targeting InhA for TB therapy

Tuberculosis (TB) is described as lethal disease in the world. Resistant to TB drugs is the main reason to have unfavourable outcomes in the treatment of TB. Therefore, new agents to replace existing drugs are urgently needed. Previous reports suggested that InhA inhibitors, an enoyl-ACP-reductase, might provide auspicious candidates which can be developed into novel antitubercular agents. In this review, we explain the role of InhA in the resistance of isoniazid. Furthermore, five classes of InhA inhibitors, which display novel binding modes and deliver evidence of their prosperous target engagement, have been debated.     

Umweltzonen in Deutschland

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Umweltzonen (UWZ) wurden als Maßnahme zur Verbesserung der Luftqualität eingeführt. In Deutschland sind derzeit...     

Arzneimitteltherapiesicherheit bei Heimbewohnern

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Bedingt durch den demografischen Wandel nimmt die Anzahl an älteren, pflegebedürftigen Menschen in Deutschland stetig...     

Small area estimation of under-5 mortality in Bangladesh,Cameroon, Chad,Mozambique, Uganda,and Zambia using spatially misaligned data

Background

The under-5 mortality rate (U5MR) is an important metric of child health and survival. Country-level estimates of U5MR are readily available, but efforts to estimate U5MR subnationally have been limited, in part, due to spatial misalignment of available data sources (e.g., use of different administrative levels, or as a result of historical boundary changes).

Methods

We analyzed all available complete and summary birth history data in surveys and censuses in six countries (Bangladesh, Cameroon, Chad, Mozambique, Uganda, and Zambia) at the finest geographic level available in each data source. We then developed small area estimation models capable of incorporating spatially misaligned data. These small area estimation models were applied to the birth history data in order to estimate trends in U5MR from 1980 to 2015 at the second administrative level in Cameroon, Chad, Mozambique, Uganda, and Zambia and at the third administrative level in Bangladesh.

Results

We found substantial variation in U5MR in all six countries: there was more than a two-fold difference in U5MR between the area with the highest rate and the area with the lowest rate in every country. All areas in all countries experienced declines in U5MR between 1980 and 2015, but the degree varied both within and between countries. In Cameroon, Chad, Mozambique, and Zambia we found areas with U5MRs in 2015 that were higher than in other parts of the same country in 1980. Comparing subnational U5MR to country-level targets for the Millennium Development Goals (MDG), we find that 12.8% of areas in Bangladesh did not meet the country-level target, although the country as whole did. A minority of areas in Chad, Mozambique, Uganda, and Zambia met the country-level MDG targets while these countries as a whole did not.

Conclusions

Subnational estimates of U5MR reveal significant within-country variation. These estimates could be used for identifying high-need areas and positive deviants, tracking trends in geographic inequalities, and evaluating progress towards international development targets such as the Sustainable Development Goals.

     

Spatial analyzes of HLA data in Rio Grande do Sul,south Brazil: genetic structure and possible correlation with autoimmune diseases

Background

HLA genes are the most polymorphic of the human genome and have distinct allelic frequencies in populations of different geographical regions of the world, serving as genetic markers in ancestry studies. In addition, specific HLA alleles may be associated with various autoimmune and infectious diseases. The bone marrow donor registry in Brazil is the third largest in the world, and it counts with genetic typing of HLA-A, -B, and -DRB1. Since 1991 Brazil has maintained the DATASUS database, a system fed with epidemiological and health data from compulsory registration throughout the country.

Methods

In this work, we perform spatial analysis and georeferencing of HLA genetic data from more than 86,000 bone marrow donors from Rio Grande do Sul (RS) and data of hospitalization for rheumatoid arthritis, multiple sclerosis and Crohn’s disease in RS, comprising the period from 1995 to 2016 obtained through the DATASUS system. The allele frequencies were georeferenced using Empirical Bayesian Kriging; the diseases prevalence were georeferenced using Inverse Distance Weighted and cluster analysis for both allele and disease were performed using Getis-Ord Gi* method. Spearman’s test was used to test the correlation between each allele and disease.

Results

The results indicate a HLA genetic structure compatible with the history of RS colonization, where it is possible to observe differentiation between regions that underwent different colonization processes. Spatial analyzes of autoimmune disease hospitalization data were performed revealing clusters for different regions of the state for each disease analyzed. The correlation test between allelic frequency and the occurrence of autoimmune diseases indicated a significant correlation between the HLA-B*08 allele and rheumatoid arthritis.

Conclusions

Genetic mapping of populations and the spatial analyzes such as those performed in this work have great economic relevance and can be very useful in the formulation of public health campaigns and policies, contributing to the planning and adjustment of clinical actions, as well as informing and educating professionals and the population.

     

Surface electromyography, force and single motor-unit data for inhibitory reflex responses in human masseter at two levels of excitatory drive

The inhibitory reflex response evoked by mildly noxious lip stimulation was tested in up to 100 trials at two different levels of pre-stimulus excitation. To regulate that excitation, the subject voluntarily controlled the firing rate of one motor neurone at 10 Hz, and then at 15 Hz while the reflex was tested. When the frequency of the motor-unit action potential (MUAP) in the controlled unit increased or decreased, the frequency of other active units' MUAPs also changed in parallel: that is, the frequency of one MUAP was an index of whole muscle excitation. The inhibitory response in the surface electromyogram (EMG) was quantitated by rectifying and averaging the signal, and by measuring its depth and area. The best correlation between the responses evoked in single units and the response in the whole muscle EMG at the two levels of excitation was obtained when the area of inhibition in the surface record was normalized to the pre-stimulus EMG level. The inhibitory response to lip stimulation in the masseter EMG decreased when the level of pre-stimulus excitation in the muscle was increased. This was confirmed using the reflex response in the averaged force data. The findings suggest that controlling one motor unit's firing rate is a useful method for controlling the whole-muscle excitation in quantitative reflex studies.     

Kieferorthopädische Behandlung erwachsener Patienten-Beraten und Überwachen

Zusammenfassung Die Beratung und Betreuung von erwachsenen Patienten sollte dem Prinzip der partnerschaftlichen Kommunikation und Interaktion folgen und den Erwachsenen in den Stand setzen, eigenständig in Kenntnis der Vorteile und Nachteile einer kieferorthopädischen Behandlung zu entscheiden und einsichtig am Prozedere der Behandlung nach Maßgabe der vom Patienten zu erbringenden Leistungen zu partizipieren.

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Summary Advising and taking care of adult patients should be a principle of partnership communication. The adult must be informed as to the nature of the orthodontic treatment planned, the advantages and disadvantages. Thereby the patient is in a position to make a decision and is aware of the degree of participation needed to ensure a successful outcome of treatment.

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Résumé Lors de la consultation et du traitement de patients adultes, il est nécessaire qu'il s'établisse un contact et un engagement réciproques. Ceci permettrait aux patients de se décider en toute indépendance, en connaissant les avantages et désavantages d'un traitement orthodontique et en prenant une part active au traitement.

     

Three-dimensional morphology of the palate in subjects with isolated cleft palate at the stage of permanent dentition.

OBJECTIVE: Three-dimensional analysis of palate size and shape in patients with isolated cleft palate at the stage of permanent dentition. DESIGN: Cross-sectional study using Fourier transform profilometry.Subjects: Twenty-nine randomly selected dental casts of approximately 15-year-old boys with isolated cleft palate and 28 dental casts of normal boys of the same age.Interventions: All patients were operated on by the same method (pushback and pharyngeal flap surgery) at a mean age of 4.5 years. MAIN OUTCOME MEASURES: Data on the palate height in 210 defined locations (pixels). RESULTS: The palate in isolated clefts is narrower throughout its whole extent and lower from the level of the first premolars. The difference, as compared with controls, increases in a posterior direction. At the level of the first molars, palatal height is reduced by one-quarter, the area of the transversal section by more than one-third. The shaping of the palate vault is, on average, symmetrical with a marked interindividual variability. Palatal height does not depend on the width of the dentoalveolar arch, and the height of the primary palate is not reduced. CONCLUSION: The smaller width and reduced height from the level of the first premolars posteriorly confirm the substantially reduced space available for the tongue in patients with isolated cleft palate. Deviations are on the average symmetrical, and the anterior part of the palate is not shallower.