Multidrug-resistant tuberculosis: case reports study in a central state of Brazil

Multidrug-resistant tuberculosis (MDR-TB) is an emerging and worrisome health problem that threatens tuberculosis (TB) control worldwide. The clinical management of MDR-TB is a complex issue associated with the use of multiple drugs for a long period, usually accompanied by side effects and high costs. The objective of this work was to relate cases of MDR-TB occurring in Goiás, a central state of Brazil. We related five cases of MDR-TB, three women and two men. All were pulmonary cases. Three were in their second treatment and two in their first treatment. Surgical pulmonary resection was performed in one case. One death occurred. Lack of adherence, gastric intolerance to anti-TB drugs and poor clinical management were the main aspects related to the emergent resistance. A revision of the main clinical aspects of this disease was performed.     

Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease

Abstract

Cardiomyopathies are an important cause of heart failure and sudden cardiac death. Little is known about the role of rare genetic variants in inflammatory cardiomyopathy. Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory cardiomyopathy prevalent in Latin America, developing in 30% of the 6 million patients chronically infected by the protozoan Trypanosoma cruzi, while 60% remain free of heart disease (asymptomatic (ASY)). The cytokine interferon-γ and mitochondrial dysfunction are known to play a major pathogenetic role. Chagas disease provides a unique model to probe for genetic variants involved in inflammatory cardiomyopathy.

Methods

We used whole exome sequencing to study nuclear families containing multiple cases of Chagas disease. We searched for rare pathogenic variants shared by all family members with CCC but absent in infected ASY siblings and in unrelated ASY.

Results

We identified heterozygous, pathogenic variants linked to CCC in all tested families on 22 distinct genes, from which 20 were mitochondrial or inflammation-related – most of the latter involved in proinflammatory cytokine production. Significantly, incubation with IFN-γ on a human cardiomyocyte line treated with an inhibitor of dihydroorotate dehydrogenase brequinar (enzyme showing a loss-of-function variant in one family) markedly reduced mitochondrial membrane potential (ΔψM), indicating mitochondrial dysfunction.

Conclusion

Mitochondrial dysfunction and inflammation may be genetically determined in CCC, driven by rare genetic variants. We hypothesize that CCC-linked genetic variants increase mitochondrial susceptibility to IFN-γ-induced damage in the myocardium, leading to the cardiomyopathy phenotype in Chagas disease. This mechanism may also be operative in other inflammatory cardiomyopathies.

     

Genetic variation involved in the risk to external apical root resorption in orthodontic patients: a systematic review

Clinical Oral Investigations - To perform a systematic review/meta-analysis to elucidate the scientific basis for the association between genetic variations and risk of external apical root...     

Effectiveness of a reciprocating single file,single cone endodontic treatment approach: a randomized controlled pragmatic clinical trial

Clinical Oral Investigations - To compare the root filling quality, the sealer extrusion, and the healing rates of apical lesions addressed via two endodontic treatment approaches. The hypothesis...