Health

Plasma melatonin is reduced in Huntington's disease
This study was undertaken to determine whether the production of melatonin, a hormone regulating sleep in relation to the light/dark cycle, is altered in Huntington's disease. We analyzed the circadian rhythm of melatonin in a 24-hour study of cohorts of control, premanifest, and stage II/III Huntington's disease subjects. The mean and acrophase melatonin concentrations were significantly reduc...


Phenotypic variability of PINK1 expression: 12 Years' clinical follow-up of two Italian families
Mutations in the PINK1 gene are the second most frequent cause of autosomal recessive early-onset parkinsonism. We evaluated five affected PINK1 homozygous and 14 heterozygous mutation carriers from two large Italian families over a 12-year follow-up period. Motor, nonmotor, cognitive, psychiatric, and behavioral profiles were systematically assessed. Four homozygotes and eight heterozygotes un...
Diagnostic criteria for Huntington's disease based on natural history
Huntington's disease (HD) is currently diagnosed based on the presence of motor signs indicating 99% “diagnostic confidence” for HD. Recent advances in the understanding of HD natural history and neurobiology indicate that disease-related brain changes begin at least 12 to 15 years before the formal diagnosis based on motor onset. Furthermore, subtle motor dysfunction, cognitive changes, an...


Current therapeutic options for Huntington's disease: Good clinical practice versus evidence-based approaches?
Therapeutic decision-making in Huntington's disease (HD) is often guided by clinical experience, because of the limited empirical evidence available. The only medication for HD that has met the regulatory hurdle for approval is tetrabenazine, indicated for the treatment of chorea. However, its use has limitations, and in the setting of specific contraindications or comorbidities the treatment o...
Huntingtin-lowering strategies in Huntingon's disease: Antisense oligonucleotides, small RNAs, and gene editing
The idea to lower mutant huntingtin is especially appealing in Huntington's disease (HD). It is autosomal dominant, so that expression of the mutant allele causes the disease. Advances in RNA and gene regulation provide foundations for the huntingtin gene (both normal and mutant alleles) and possibly the mutant allele only. There is much preclinical animal work to support the concept of gene an...


Poor Agreement Between Dialysis Unit Blood Pressure and Interdialytic Ambulatory Blood Pressure
Although ambulatory blood pressure (ABP) monitoring (ABPM) is often considered to have an advantage over dialysis unit blood pressure (BP) in dialysis patients, the exact relationship between these two measurements of BP has not been well determined. In a cohort of 90 Chinese dialysis patients, agreement between dialysis unit BP (predialysis and postdialysis BP) and interdialytic ABP was evalua...
Predictors of functional deterioration in Chinese patients with Psoriatic arthritis: a longitudinal study
Psoriatic arthritis (PsA) disease activities at baseline may determine physical function over time. There is no longitudinal data on course of physical function in PsA patients from Asia. We aim to describe variables associated with a deterioration of physical function in PsA in Chinese over a 6-year period. 125 consecutive patients with PsA fulfilled the CASPAR criteria from a rheumatology out...

Upper body and lower limbs musculoskeletal symptoms and health inequalities in Europe. An analysis of cross-sectional data
Musculoskeletal disorders are the most frequent occupational diseases in Europe. However, their multifactorial aetiology poses several challenges concerning not only the estimation of relative prevalence rates across occupational groups but also how the co-occurrence of known risk factors might differ between disorders of the upper and lower limbs. Against this background, the following objecti...
Sleep and moral awareness
The implications of sleep for morality are only starting to be explored. Extending the ethics literature, we contend that because bringing morality to conscious attention requires effort, a lack of sleep leads to low moral awareness. We test this prediction with three studies. A laboratory study with a manipulation of sleep across 90 participants judging a scenario for moral content indicates t...

Topographic sleep EEG changes in the acute and chronic stage of hemispheric stroke
After stroke, the injured brain undergoes extensive reorganization and reconnection. Sleep may play a role in synaptic plasticity underlying stroke recovery. To test this hypothesis, we investigated topographic sleep electroencephalographic characteristics, as a measure of brain reorganization, in the acute and chronic stages after hemispheric stroke. We studied eight patients with unilateral s...
Influence of insulin-like growth factor I overexpression via recombinant adeno-associated vector gene transfer upon the biological activities and differentiation potential of human bone marrow-derived mesenchymal stem cells
The transplantation of genetically modified progenitor cells such as bone marrow-derived mesenchymal stem cells (MSCs) is an attractive strategy to improve the natural healing of articular cartilage defects. In the present study, we examined the potential benefits of sustained overexpression of the mitogenic and pro-anabolic insulin-like growth factor I (IGF-I) via gene transfer upon the biolog...

TNFalpha and IL-1beta influence the differentiation and migration of murine MSCs independently of the NF-kappaB pathway
Mesenchymal stem cells (MSC) have the ability to repair and regenerate tissue, home to sites of inflammation and evade the host immune system. As such, they represent an attractive therapy for the treatment of autoimmune inflammatory diseases. However; results from in-vivo murine studies in inflammatory arthritis have been conflicting, which may be due to the genetic background of the MSC used....
Role of explicit verbal information in conditioned analgesia
The exact role of expectation in conditioned analgesia is still elusive as it is not clear whether conditioning is an automatic process or rather it is cognitively mediated. This study is aimed at understanding the role of explicit verbal information in conditioned analgesia. Two groups of healthy subjects received a conditioning procedure whereby two visual cues were paired with increase and d...
Repeated intra-articular injections of acidic saline produce long-lasting joint pain and widespread hyperalgesia
Synovial fluid in inflamed joint shows a drop in pH, which activates proton-gated ion channels in nociceptors. No studies have ever tried to develop and characterize acid-induced joint pain. Rats were injected intra-articularly with pH 4.0 acidic saline twice, 5 days apart. Pain-related behaviour tests including weight-bearing asymmetry, paw withdrawal threshold and knee compression threshold...
Differential effects of voltage-gated calcium channel blockers on calcium channel alpha-2-delta-1 subunit protein-mediated nociception
Overexpression of the voltage-gated calcium channel (VGCC) alpha-2-delta1 subunit protein (Cavα2δ1) has been shown to cause pain states. However, whether VGCC are involved in pain states driven by abnormal Cavα2δ1 expression is not known. Intrathecal injection of N-, P/Q- and L-type VGCC blockers were tested in two models: a transgenic neuronal Cavα2δ1 overexpression (TG) model with behav...