Fasciculation differences between ALS and non-ALS patients: an ultrasound study.

BACKGROUND: Fasciculation is an important sign for the diagnosis of amyotrophic lateral sclerosis (ALS). Our study aimed to analyze the difference in fasciculation detected with muscle ultrasonography (MUS) between ALS patients and non-ALS patients with symptoms resembling ALS. METHODS: Eighty-eight ALS patients and fifty-four non-ALS (eight multifocal motor neuropathy, 32 chronic inflammatory demyelinating polyneuropathy/Charcot-Marie-Tooth, and 14 cervical spondylopathy or lumbar spondylopathy) patients were recruited. MUS was performed on 19 muscle groups in cervical, lumbosacral, bulbar, and thoracic regions for each patient. The intensity of fasciculation was divided into five grades based on firing frequency and number in the involved muscle groups. RESULTS: The overall detection rates were 72.8% in ALS and 18% in non-ALS patients. The fasciculation grades (median [IQR]) were 2 (0-3) in ALS and 0 (0-0) in non-ALS patients (P < 0.001). Fasciculations were observed in four regions for ALS patients and primarily distributed in proximal limbs. Fasciculations in non-ALS patients were primarily low-grade and mostly distributed in distal limbs. DISCUSSION: The fasciculation grade was higher in ALS than non-ALS patients. The distribution pattern of fasciculation was different between ALS and non-ALS patients. CONCLUSIONS: The fasciculation grade and distribution pattern detected with MUS could help distinguish ALS from non-ALS patients.

Thermal stability of purified and reconstituted CFTR in a locked open channel conformation.

CFTR is unique among ABC transporters as the only one functioning as an ion channel and from a human health perspective because mutations in its gene cause cystic fibrosis. Although considerable advances have been made towards understanding CFTR's mechanism of action and the impact of mutations, the lack of a high-resolution 3D structure has hindered progress. The large multi-domain membrane glycoprotein is normally present at low copy number and when over expressed at high levels it aggregates strongly, limiting the production of stable mono-disperse preparations. While the reasons for the strong self-association are not fully understood, its relatively low thermal stability seems likely to be one. The major CF causing mutation, ΔF508, renders the protein very thermally unstable and therefore a great deal of attention has been paid to this property of CFTR. Multiple second site mutations of CFTR in NBD1 where F508 normally resides and small molecule binders of the domain increase the thermal stability of the mutant. These manipulations also stabilize the wild-type protein. Here we have applied ΔF508-stabilizing changes and other modifications to generate wild-type constructs that express at much higher levels in scaled-up suspension cultures of mammalian cells. After purification and reconstitution into liposomes these proteins are active in a locked-open conformation at temperatures as high as 50 °C and remain monodisperse at 4 °C in detergent or lipid for at least a week. The availability of adequate amounts of these and related stable active preparations of homogeneous CFTR will enable stalled structural and ligand binding studies to proceed.

Fabrication of alginate-based multi-crosslinked biomembranes for direct methanol fuel cell application.

The alginate-based multi-crosslinked biomembranes (ABMCBs) were prepared mainly with sodium alginate as matrix and self-made functionalized organosilane containing different groups as additive. The properties of ABMCBs with various additive loading were investigated as proton exchange membranes (PEMs). The results showed that higher water absorption and lower swelling were obtained simultaneously with increasing additive loading, which is very beneficial to the use of PEMs. The ABMCB-4 containing 40 wt% additive exhibited the optimal selectivity and maximum power density, which were obviously higher than that of commercial Nafion@ 117. Furthermore, ABMCB-4 possessed excellent mechanical property, methanol barrier and stability, indicating its potential adaptability as PEM for direct methanol fuel cell application.

Fabrication of silicon/polymer composite nanopost arrays and their sensing applications.

A novel technique is reported for fabricating silicon/polymer composite nanopost arrays by combining colloidal lithography and surface-initiated atom-transfer radical polymerization. The composite nanopost arrays possess a core/shell nanoarchitecture, with shells of poly(2-hydroxyethyl methacrylate) and cores of silicon nanoposts. The polymer brush possesses quasi-3D homogeneous nanoarchitectures due to the controllable polymerization process using the surface-initiated atom-transfer radical polymerization technique. The composite nanopost arrays are durable due to the particular nanoarchitectures. The backbone templates of the composites are silicon nanopost arrays directly etched from silicon substrates, and the polymer shell is covalently grafted from the arrays. The composite nanopost arrays exhibit vivid colors. Moreover, the colors of the composite nanopost arrays can be tuned from green to red by changing the thickness of fi lm. Specifically, the composite nanopost arrays can be used as sensors to rapidly detect water vapors with high stability and reproducibility. Many different functional surfaces could be prepared through this technique using other functional monomers.

Reference values for lower limb nerve ultrasound and its diagnostic sensitivity.

We aimed to establish the cross-sectional area (CSA) reference values for peripheral nerves of lower extremities in a healthy Chinese population, and to determine their diagnostic values for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Charcot-Marie-Tooth disease type1A (CMT1A). One hundred eleven healthy subjects, 15-70 years of age, as well as 104 CIDP patients and 26 CMT1A patients were recruited. CSA at predetermined sites of the tibial, fibular, sciatic and sural nerves was measured. The CSA of the tibial nerve ranged from 10.2 ± 1.9 to 20.7 ± 3.6 mm2, and for fibular nerve from 8.4 ± 1.8 to 9.5 ± 1.9 mm2. 86% CIDP patients had upper limb nerve enlargement, while only 67% had lower limb nerve enlargement. In CIDP patients with normal upper limb ultrasound, 56% (5/9) would have lower limb nerve enlargement. All CMT1A patients had both upper and lower limb nerve enlargement. Addition of lower limb nerve ultrasound showed no added value in diagnosis of CMT1A, but could be supplementary for CIDP when upper limb ultrasound is normal.

Vagus Nerve Ultrasound in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Charcot-Marie-Tooth Disease Type 1A.

BACKGROUND AND PURPOSE: Both clinical autonomic dysfunction and involvement of autonomic nerves have been reported in a range of peripheral nerve disorders. We employed nerve ultrasound to assess the size of the vagus nerve in a serial study of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Charcot-Marie-Tooth type 1B (CMT1B) as compared to healthy controls (HCs). We correlated these findings with involvement of the median and ulnar nerves. METHODS: Forty-three patients with CIDP, 8 with CMT1A, and 105 HC were prospectively recruited. The cross-sectional areas (CSAs) of the vagus, median, and ulnar nerves were measured bilaterally. The alteration of CSA of those nerves was followed longitudinally in CIDP. RESULTS: The median (range) CSA of the vagus nerve was 2 (1-28) mm2 in CIDP, 3 (2-6) mm2 in CMT1A, and 1 (1-2) mm2 in HC. The vagus nerve CSA was positively correlated with the maximum CSA of median/ulnar nerve in CIDP and CMT1A. The alteration in vagus nerve CSA was positively correlated with the alteration in mean median/ulnar nerve CSA in CIDP during follow-up. CONCLUSIONS: The vagus nerve was involved to a similar extent as the median and ulnar nerves in CIDP and CMT1A, although no symptoms or signs of vagus nerve involvement were found. Further study should be performed to explore the clinical relevance of vagus nerve enlargement in these disorders.

Multiple Sites Ultrasonography of Peripheral Nerves in Differentiating Charcot-Marie-Tooth Type 1A from Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

INTRODUCTION: Multiple sites measurement of cross-sectional areas (CSA) by ultrasound was performed to differentiate Charcot-Marie-Tooth type 1A (CMT1A) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Nine patients with CMT1A, 28 patients with CIDP, and 14 healthy controls (HC) were recruited prospectively. Consecutive ultrasonography scanning was performed from wrist to axilla on median and ulnar nerves. CSAs were measured at 10 predetermined sites of each nerve. RESULTS: CMT1A had significantly larger CSAs at all sites of median and ulnar nerves (p < 0.01). In CMT1A, CSAs increased gradually and homogeneously from distal to proximal along the nerve, except potential entrapment sites. CIDP displayed three different morphological patterns, including mild enlargement in 15 patients, prominent segmental enlargement in 12, and slight enlargement in 1, among which different treatment responses were observed. All patients with mild nerve enlargement treated with intravenous immunoglobulin were responsive (7/7), while less than half of those with prominent segmental enlargement (3/7) were responsive (p < 0.01). DISCUSSION: Consecutive scan along the nerve and multiple sites measurement by ultrasound could supply more detailed morphological feature of the nerve and help to differentiate CMT1A from CIDP.