The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease

Neuronal intermediate filament inclusion disease (NIFID), a rare form of frontotemporal lobar degeneration (FTLD), is characterized neuropathologically by focal atrophy of the frontal and temporal lobes, neuronal loss, gliosis, and neuronal cytoplasmic inclusions (NCI) containing epitopes of ubiquitin and neuronal intermediate filament proteins. Recently, the 'fused in sarcoma' (FUS) protein (encoded by the FUS gene) has been shown to be a component of the inclusions of familial amyotrophic lateral sclerosis with FUS mutation, NIFID, basophilic inclusion body disease, and atypical FTLD with ubiquitin-immunoreactive inclusions (aFTLD-U). To further characterize FUS proteinopathy in NIFID, and to determine whether the pathology revealed by FUS immunohistochemistry (IHC) is more extensive than a-internexin, we have undertaken a quantitative assessment of ten clinically and neuropathologically well-characterized cases using FUS IHC. The densities of NCI were greatest in the dentate gyrus (DG) and in sectors CA1/2 of the hippocampus. Anti-FUS antibodies also labeled glial inclusions (GI), neuronal intranuclear inclusions (NII), and dystrophic neurites (DN). Vacuolation was extensive across upper and lower cortical layers. Significantly greater densities of abnormally enlarged neurons and glial cell nuclei were present in the lower compared with the upper cortical laminae. FUS IHC revealed significantly greater numbers of NCI in all brain regions especially the DG. Our data suggest: (1) significant densities of FUS-immunoreactive NCI in NIFID especially in the DG and CA1/2; (2) infrequent FUS-immunoreactive GI, NII, and DN; (3) widely distributed vacuolation across the cortex, and (4) significantly more NCI revealed by FUS than a-internexin IHC.

Whole body vibration treatments in postmenopausal women can improve bone mineral density:results of a stimulus focussed meta-analysis

Whole body vibration treatment is a non-pharmacological intervention intended to stimulate muscular response and increase bone mineral density, particularly for postmenopausal women. The literature related to this topic is controversial, heterogeneous, and unclear despite the prospect of a major clinical effect. The aim of this study was to identify and systematically review the literature to assess the effect of whole body vibration treatments on bone mineral density (BMD) in postmenopausal women with a specific focus on the experimental factors that influence the stimulus. Nine studies fulfilled the inclusion criteria, including 527 postmenopausal women and different vibration delivery designs. Cumulative dose, amplitudes and frequency of treatments as well as subject posture during treatment vary widely among studies. Some of the studies included an associated exercise training regime. Both randomized and controlled clinical trials were included. Whole body vibration was shown to produce significant BMD improvements on the hip and spine when compared to no intervention. Conversely, treatment associated with exercise training resulted in negligible outcomes when compared to exercise training or to placebo. Moreover, side-alternating platforms were more effective in improving BMD values than synchronous platforms and mechanical oscillations of magnitude higher than 3 g and/or frequency lower than 25 Hz were also found to be effective. Treatments with a cumulative dose over 1000 minutes in the follow-up period were correlated to positive outcomes. Our conclusion is that whole body vibration treatments in elderly women can reduce BMD decline.However, many factors (e.g. amplitude, frequency and subject posture) affect the capacity of the vibrations to propagate to the target site; the adequate level of stimulation required to produce these effects has not yet been defined. Further biomechanical analyses to predict the propagation of the vibration waves along the body and assess the stimulation levels are required.