Sexual dimorphism in SLE: above and beyond sex hormones.

Systemic lupus erythematosus (SLE) is characterized by aberrant production of auto-antibodies and a sexual dimorphism both in the phenotypic expression and frequency of the disease between males and females. The striking female predominance was initially attributed primarily to sex hormones. However, recent data challenge this simplistic view and point more towards genetic and epigenetic factors accounting for this difference. More specifically, several SLE-associated single-nucleotide polymorphisms (SNPs) have been found to play an important role in the gender predilection in SLE. Their effect is mediated through their involvement in sex-hormone and immune system signalling and dysregulation of the expression of genes and miRNAs pertinent to the immune system. Additionally, the genetic factors are interchangeably associated with epigenetic modifications such as DNA methylation and histone modification, thus revealing a highly complex network of responsible mechanisms. Of importance, disturbance in the epigenetic process of X chromosome inactivation in females as well as in rare X chromosome abnormalities leads to increased expression of X-linked immune-related genes and miRNAs, which might predispose females to SLE. Microbiota dysbiosis has also been implicated in the sexual dimorphism by the production of oestrogens within the gut and the regulation of oestrogen-responsive immune-related genes. Sexual dimorphism in SLE is an area of active research, and elucidation of its molecular basis may facilitate ongoing efforts towards personalized care.

Effects of ventral intermediate nucleus deep brain stimulation across multiple effectors in essential tremor.

OBJECTIVE: Essential tremor (ET) prominently affects the upper-limbs during voluntary movements, but can also affect the lower-limbs, head, and chin. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of thalamus improves both clinical ratings and quantitative measures of tremor, no study has quantified effects of DBS on tremor across multiple body parts. Our objective was to quantify therapeutic effects of DBS across multiple body parts in ET. METHODS: We performed quantitative assessment of tremor in ET patients who had DBS for at least one year. We assessed tremor on and off VIM-stimulation using triaxial accelerometers on the upper-limbs, lower-limbs, head and chin during seated and standing tasks. RESULTS: VIM-DBS significantly reduced tremor, but there was no statistical difference in degree of tremor reduction across the measured effectors. Compared to healthy controls, ET patients treated with DBS showed significantly greater tremor power (4-8 Hz) across all effectors during seated and standing tasks. CONCLUSIONS: VIM-DBS reduced tremor in ET patients. There was no significant difference in the degree of tremor reduction across the measured effectors. SIGNIFICANCE: This study provides new quantitative evidence that VIM-DBS is effective at reducing tremor across multiple parts of the body.

Old adults exhibit greater motor output variability than young adults only during rapid discrete isometric contractions.

The purpose of this study was to examine the ability of young and elderly individuals to control submaximum levels of force (5-90%) during continuous and rapid discrete isometric contractions of the quadriceps femoris. Participants were 24 young (25.3 +/- 2.8 years) and 24 elderly individuals (73.3 +/- 5.5 years) that were healthy and active. The strength of elderly participants was approximately 40% lower than young participants. The standard deviation and coefficient of variation (CV) of force were greater during discrete contractions than during continuous isometric contractions. During continuous isometric contractions, young and elderly participants exhibited similar CVs of force. During discrete contractions, however, elderly participants exhibited greater CVs for peak force and impulse and greater standard deviations and CVs for temporal characteristics than young participants. Results suggest that the control of force in active elderly people declines only during rapid discrete contractions and that this decline may be associated with declines in temporal characteristics of the force production.