Mismatch repair (MMR) is a near ubiquitous pathway, essential for the maintenance of genome stability. Members of the MutS and MutL protein families perform key steps in mismatch correction. Despite the major importance of this repair pathway, MutS–MutL are absent in almost all Actinobacteria and many Archaea. However, these organisms exhibit rates and spectra of spontaneous mutations similar to MMR-bearing species, suggesting the existence of an alternative to the canonical MutS–MutL-based MMR. Here we report that Mycobacterium smegmatis NucS/EndoMS, a putative endonuclease with no structural homology to known MMR factors, is required for mutation avoidance and anti-recombination, hallmarks of the canonical MMR. Furthermore, phenotypic analysis of naturally occurring polymorphic NucS in a M. smegmatis surrogate model, suggests the existence of M. tuberculosis mutator strains. The phylogenetic analysis of NucS indicates a complex evolutionary process leading to a disperse distribution pattern in prokaryotes. Together, these findings indicate that distinct pathways for MMR have evolved at least twice in nature.

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We report the results of administration of the Portuguese-Brazilian translation of the Liverpool Adverse Events Profile (LAEP) to 100 patients (mean age=34.5, SD=12.12; 56 females), 61 with symptomatic partial epilepsy (SPE) and 39 with idiopathic generalized epilepsy (IGE) (ILAE, 1989) who were on a stable antiepileptic drug (AED) regimen and being treated in a Brazilian tertiary epilepsy center. Carbamazepine was the most commonly used AED (43.0%), followed by valproic acid (32.0%). Two or more AEDs were used by 69.0% of patients. The mean LAEP score (19 questions) was 37.6 (SD=13.35). The most common adverse effects were sleepiness (35.0%), memory problems (35.0%), and difficulty in concentrating (25.0%). Higher LAEP scores were associated with polytherapy with three or more AEDs (P=0.005), female gender (P<0.001), older age (P<0.001), and uncontrolled seizures (P=0.045). The intraclass coefficient (test-retest reliability) for LAEP overall score was 0.848 (95% CI=0.782-0.895), with a range from 0.370 (unsteadiness) to 0.750 (memory problems). Cronbach's α coefficient (internal consistency) was 0.903. The LAEP was highly correlated with Quality of Life in Epilepsy-31 inventory (r=-0.804, P>0.001) and Hospital Anxiety and Depression Scale (Depression: r=0.637, P<0.001; Anxiety: r=0.621, P<0.001) dimensions. LAEP overall scores were similar in people with SPE and IGE and were not helpful in differentiating adverse effects in these two groups. Clinical variables that influenced global LAEP were seizure frequency (P=0.050) and generalized tonic-clonic seizures in the last month (P=0.031) in the IGE group, and polytherapy with three or more AEDs (P=0.003 and P=0.003) in both IGE and SPE groups.

INTRODUÇÃO: O padrão de relacionamento que se estabelece entre paciente e cuidador pode comprometer a qualidade de vida e o crescimento de ambos. OBJETIVO: Comparar a qualidade de vida e a sobrecarga dos cuidadores de pacientes com epilepsia do lobo temporal (ELT) com esclerose mesial temporal (EMT) e epilepsia mioclônica juvenil (EMJ). CASUÍSTICA E METODOLOGIA: Foram avaliados 20 cuidadores de pacientes com ELT e 20 cuidadores de pacientes com EMJ, com o Inventário de Qualidade de Vida SF-36 e Questionário de Sobrecarga do Cuidador ("Burden Interview" - Zarit). RESULTADOS: Houve sobrecarga leve a moderada nos dois grupos (30 no de ELT e 21 pontos para o grupo de EMJ), porém não foi observada associação estatisticamente significante entre os grupos. Ao buscarmos uma correlação entre os domínios do SF-36 e a sobrecarga do cuidador para os dois grupos estudados, observou-se apenas no grupo EMJ: estado geral de saúde (p = 0,011), limitações por aspectos emocionais (p = 0,037) e saúde mental (p = 0,002). CONCLUSÃO: Cuidadores de pacientes dos dois grupos são sobrecarregados de forma semelhante. Esta sobrecarga não interferiu significativamente na qualidade de vida dos mesmos na maioria dos domínios embora cuidadores de pacientes com EMJ tenham revelado impacto em domínios que medem aspectos da saúde emocional e física.