Demystifying the spontaneous phenomena of motor hyperexcitability.

Possessing a discrete functional repertoire, the anterior horn cell can be in one of two electrophysiological states: on or off. Usually under tight regulatory control by the central nervous system, a hierarchical network of these specialist neurons ensures muscular strength is coordinated, gradated and adaptable. However, spontaneous activation of these cells and their axons can result in abnormal muscular twitching. The muscular twitch is the common building block of several distinct clinical patterns, namely fasciculation, myokymia and neuromyotonia. When attempting to distinguish these entities electromyographically, their unique temporal and morphological profiles must be appreciated. Detection and quantification of burst duration, firing frequency, multiplet patterns and amplitude are informative. A common feature is their persistence during sleep. In this review, we explain the accepted terminology used to describe the spontaneous phenomena of motor hyperexcitability, highlighting potential pitfalls amidst a bemusing and complex collection of overlapping terms. We outline the relevance of these findings within the context of disease, principally amyotrophic lateral sclerosis, Isaacs syndrome and Morvan syndrome. In addition, we highlight the use of high-density surface electromyography, suggesting that more widespread use of this non-invasive technique is likely to provide an enhanced understanding of these motor hyperexcitability syndromes.

Preference evaluation of ground beef by untrained subjects with three levels of finely textured beef.

After receiving bad publicity in 2012 and being removed from many ground beef products, finely textured beef (referred to as 'pink slime' by some) is making a comeback. Some of its proponents argue that consumers prefer ground beef containing finely textured beef, but no objective scientific party has tested this claim-that is the purpose of the present study. Over 200 untrained subjects participated in a sensory analysis in which they tasted one ground beef sample with no finely textured beef, another with 15% finely textured beef (by weight), and another with more than 15%. Beef with 15% finely textured beef has an improved juiciness (p < 0.01) and tenderness (p < 0.01) quality. However, subjects rate the flavor-liking and overall likeability the same regardless of the finely textured beef content. Moreover, when the three beef types are consumed as part of a slider (small hamburger), subjects are indifferent to the level of finely textured beef.

Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis.

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are a common cause of neuromuscular disease, ranging from various congenital myopathies to the malignant hyperthermia (MH) susceptibility trait without associated weakness. We sequenced RYR1 in 39 unrelated families with rhabdomyolysis and/or exertional myalgia, frequent presentations in the neuromuscular clinic that often remain unexplained despite extensive investigations. We identified 9 heterozygous RYR1 mutations/variants in 14 families, 5 of them (p.Lys1393Arg; p.Gly2434Arg; p.Thr4288_Ala4290dup; p.Ala4295Val; and p.Arg4737Gln) previously associated with MH. Index cases presented from 3 to 45 years with rhabdomyolysis, with or without exertional myalgia (n=12), or isolated exertional myalgia (n=2). Rhabdomyolysis was commonly triggered by exercise and heat and, less frequently, viral infections, alcohol and drugs. Most cases were normally strong and had no personal MH history. Inconsistent additional features included heat intolerance, and cold-induced muscle stiffness. Muscle biopsies showed mainly subtle changes. Familial RYR1 mutations were confirmed in relatives with similar or no symptoms. These findings suggest that RYR1 mutations may account for a substantial proportion of patients presenting with unexplained rhabdomyolysis and/or exertional myalgia. Associated clinico-pathological features may be subtle and require a high degree of suspicion. Additional family studies are paramount in order to identify potentially MH susceptible relatives.

Production costs and animal welfare for four stylized hog production systems.

Nonhuman animal welfare is arguably the most contentious issue facing the hog industry. Animal advocacy groups influence the regulation of hog farms and induce some consumers to demand more humane pork products. Hog producers are understandably reluctant to improve animal well being unless the premium they extract exceeds the corresponding increase in cost. To better understand the relationship between animal welfare and production costs under different farm systems, this study investigates 4 stylized hog production systems. The results show that increasing animal welfare for all hogs in the United States will increase retail pork prices by a maximum of 2% for a small welfare increase and 5% for a large welfare increase. The cost of banning gestation crates measured by this study is lower than the consumer willingness-to-pay from other studies.

A survey to determine public opinion about the ethics and governance of farm animal welfare.

OBJECTIVE: To determine the attitude of the public toward farm animal welfare and identify beliefs regarding how decisions about farm animal welfare should be made. DESIGN: Telephone survey. STUDY POPULATION: A random sample of 1,019 US households. PROCEDURES: US households were contacted by telephone and asked to take part in a survey consisting of 48 items. RESULTS: A majority (437/773 [56.4%]) of respondents believed decisions about farm animal welfare should be made by experts rather than being based on the views of the public. Such advocates of expert decision making were less likely to believe the government should regulate farm animal welfare. Most (420/773 [54.3%]) respondents believed decisions about farm animal welfare should be based on scientific measures of animal well-being, as opposed to moral and ethical considerations. Those individuals who believed farm animal welfare decisions should be made by experts and be based on scientific measures were the least concerned about farm animal welfare issues. People who believed animal welfare decisions should be made by experts and be based on scientific measures were most responsive to information about use of gestation crates for sows. CONCLUSIONS AND CLINICAL RELEVANCE: These results should help increase recognition that changing public opinion is not simply a matter of convincing the public to support positions established by veterinarians and animal scientists. People's views about the role of the democratic process in regulating technologic change are important determinants of whether people accept the changes in animal agriculture that have occurred during the past century.

EFNS guideline on diagnosis and management of limb girdle muscular dystrophies.

The limb girdle muscular dystrophies (LGMD) are termed as such as they share the characteristic feature of muscle weakness predominantly affecting the shoulder and pelvic girdles; their classification has been completely revised in recent years because of elucidation of many of the underlying genetic and protein alterations in the various subtypes. An array of diagnostic measures is possible but with varying ease of use and availability. Several aspects of muscle cell function appear to be involved in the causation of muscle pathology. These cellular variations may confer some specific clinical features thus permitting recognition of the LGMD subtype and hence directing appropriate levels of monitoring and intervention. Despite an extensive literature on the individual limb girdle dystrophies, these publications may be impenetrable for the general neurologist in this increasingly complex field. The proposed guidelines suggest an approach to the diagnosis and monitoring of the limb girdle dystrophies in a manner accessible to general neurologists.

Access of target groups to 1915(c) Medicaid home and community based waiver services.

OBJECTIVES: The study examined the access of specific target groups to the 1915(c) home and community based waiver program in terms of the number of participants, services, and expenditures for 1992 and 1997. METHODS: The study collected HCFA 372 waiver program statistics from each of the states and compared statistics for the two time periods. A regression examined the increase in program expenditures. RESULTS: An unequal distribution of HCBS expenditures across target groups was found where individuals with developmental disability were 39 percent of participants but used 77 percent of the total $7.9 billion waiver expenditures in 1997. The aged and disabled were 58 percent of waiver participants but received 21 percent of expenditures. The program growth was primarily due to increases in participants and reimbursement rates. CONCLUSIONS: Individuals with MR/DD used more costly services such as habilitation and residential care than other target groups. Studies are needed to examine what accounts for the unequal access and whether program expenditures are sufficient to meet the long-term care needs of various target groups.

The structure of the N-terminal actin-binding domain of human dystrophin and how mutations in this domain may cause Duchenne or Becker muscular dystrophy.

BACKGROUND: Dystrophin is an essential component of skeletal muscle cells. Its N-terminal domain binds to F-actin and its C terminus binds to the dystrophin-associated glycoprotein (DAG) complex in the membrane. Dystrophin is therefore thought to serve as a link from the actin-based cytoskeleton of the muscle cell through the plasma membrane to the extracellular matrix. Pathogenic mutations in dystrophin result in Duchenne or Becker muscular dystrophy. RESULTS: The crystal structure of the dystrophin actin-binding domain (ABD) has been determined at 2.6 A resolution. The structure is an antiparallel dimer of two ABDs each comprising two calponin homology domains (CH1 and CH2) that are linked by a central alpha helix. The CH domains are both alpha-helical globular folds. Comparisons with the structures of utrophin and fimbrin ABDs reveal that the conformations of the individual CH domains are very similar to those of dystrophin but that the arrangement of the two CH domains within the ABD is altered. The dystrophin dimer reveals a change of 72 degrees in the orientation of one pair of CH1 and CH2 domains (from different monomers) relative to the other pair when compared with the utrophin dimer. The dystrophin monomer is more elongated than the fimbrin ABD. CONCLUSIONS: The dystrophin ABD structure reveals a previously uncharacterised arrangement of the CH domains within the ABD. This observation has implications for the mechanism of actin binding by dystrophin and related proteins. Examining the position of three pathogenic missense mutations within the structure suggests that they exert their effects through misfolding of the ABD, rather than through disruption of the binding to F-actin.

The 2.0 A structure of the second calponin homology domain from the actin-binding region of the dystrophin homologue utrophin.

Utrophin is a close homologue of dystrophin, the protein defective in Duchenne muscular dystrophy. Like dystrophin, it is composed of three regions: an N-terminal region that binds actin filaments, a large central region with triple coiled-coil repeats, and a C-terminal region that interacts with components in the dystroglycan protein complex at the plasma membrane. The N-terminal actin-binding region consists of two calponin homology domains and is related to the actin-binding domains of a superfamily of proteins including alpha-actinin, spectrin and fimbrin. Here, we present the 2.0 A structure of the second calponin homology domain of utrophin solved by X-ray crystallography, and compare it to the other calponin homology domains previously determined from spectrin and fimbrin.

Crystal structure of the actin-binding region of utrophin reveals a head-to-tail dimer.

BACKGROUND: Utrophin is a large multidomain protein that belongs to a superfamily of actin-binding proteins, which includes dystrophin, alpha-actinin, beta-spectrin, fimbrin, filamin and plectin. All the members of this family contain a common actin-binding region at their N termini and perform a wide variety of roles associated with the actin cytoskeleton. Utrophin is the autosomal homologue of dystrophin, the protein defective in the X-linked Duchenne and Becker muscular dystrophies, and upregulation of utrophin has been suggested as a potential therapy for muscular dystrophy patients. RESULTS: The structure of the actin-binding region of utrophin, consisting of two calponin-homology (CH) domains, has been solved at 3.0 A resolution. It is composed of an antiparallel dimer with each of the monomers being present in an extended dumbell shape and the two CH domains being separated by a long central helix. This extended conformation is in sharp contrast to the compact monomer structure of the N-terminal actin-binding region of fimbrin. CONCLUSIONS: The crystal structure of the actin-binding region of utrophin suggests that these actin-binding domains may be more flexible than was previously thought and that this flexibility may allow domain reorganisation and play a role in the actin-binding mechanism. Thus utrophin could possibly bind to actin in an extended conformation so that the sites previously identified as being important for actin binding may be directly involved in this interaction.

Amniotic band syndrome: a population-based study in two Australian states.

A search for cases of amniotic band syndrome was made in two population-based Australian birth defects registries, using defined selection criteria. Over a period of 4 years in Western Australia and 5 years in South Australia, 25 cases of amniotic band syndrome had been identified as such by the two registries, and an additional 15 new cases were identified by the study selection process, giving an annual prevalence of amniotic band syndrome over the study period of 2.03 per 10,000 births. Similar proportions of male and female infants were affected, although the syndrome was more common in mothers younger than 25 years of age, and in first births. Limb defects only (upper and/or lower) were found in 24 cases, limb-body-wall defects in four cases, and complex craniofacial and other malformations in 12 cases. A heightened awareness of the syndrome should enhance the identification of amniotic band syndrome, which has implications for genetic counselling, and our understanding of the aetiology and pathogenesis of this condition.