bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orthopaedic issues in the musculoskeletal care of adults with cerebral palsy
Authors: HORSTMANN HELEN M , HOSALKAR HARISH , KEENAN MARY ANN 
Published: September 2009

Aims  Orthopaedic care of adults with cerebral palsy (CP) has not been well documented in orthopaedic literature. This paper focuses on some of the common problems which present themselves when adults with CP seek orthopaedic intervention. In particular, we review the most common orthopaedic issues which present to the Penn Neuro‐Orthopaedics Program.Method  A formal review of consecutive surgeries performed by the senior author on adults with CP was previously conducted. This paper focuses on the health delivery care for the adult with orthopaedic problems related to cerebral palsy. Ninety‐two percent of these patients required lower extremity surgery. Forty percent had procedures performed on the upper extremities.Results  The majority of problems seen in the Penn Neuro‐Orthopaedics Program are associated with the residuals of childhood issues, particularly deformities associated with contractures. Patients are also referred for treatment of acquired musculoskeletal problems such as degenerative arthritis of the hip or knee. A combination of problems contribute most frequently to foot deformities and pain with weight‐bearing, shoewear or both, most often due to equinovarus. The surgical correction of this is most often facilitated through a split anterior tibial tendon transfer. Posterior tibial transfers are rarely indicated. Residual equinus deformities contribute to a pes planus deformity. The split anterior tibial tendon transfer is usually combined with gastrocnemius‐soleus recession and plantar release. Transfer of the flexor digitorum longus to the os calcis is done to augment the plantar flexor power. Rigid pes planus deformity is treated with a triple arthrodesis. Resolution of deformity allows for a good base for standing, improved ability to tolerate shoewear, and/or braces. Other recurrent or unresolved issues involve hip and knee contractures. Issues of lever arm dysfunction create problems with mechanical inefficiency. Upper extremity intervention is principally to correct contractures. Internal rotation and adductor tightness at the shoulder makes for difficult underarm hygiene and predispose a patient to a spiral fracture of the humerus. A tight flexor, pronation pattern is frequently noted through the elbow and forearm with further flexion contractures through the wrist and fingers. Lengthenings are more frequently performed than tendon transfers in the upper extremity. Arthrodesis of the wrist or on rare occasions of the metacarpal‐phalangeal joints supplement the lengthenings when needed.Conclusions  The Penn Neuro‐Orthopaedics Program has successfully treated adults with both residual and acquired musculoskeletal deformities. These deformities become more critical when combined with degenerative changes, a relative increase in body mass, fatigue, and weakness associated with the aging process.
Cerebral palsy and aging
Authors: HAAK PETERSON , LENSKI MADELEINE , HIDECKER MARY JO COOLEY , LI MIN , PANETH NIGEL 
Published: September 2009

Cerebral palsy (CP), the most common major disabling motor disorder of childhood, is frequently thought of as a condition that affects only children. Deaths in children with CP, never common, have in recent years become very rare, unless the child is very severely and multiply disabled. Thus, virtually all children assigned the diagnosis of CP will survive into adulthood. Attention to the adult with CP has been sparse, and the evolution of the motor disorder as the individual moves through adolescence, young adulthood, middle age, and old age is not well understood. Nor do we know what happens to other functional domains, such as communication and eating behavior, in adults with CP. Although the brain injury that initially causes CP by definition does not progressively worsen through the lifetime, the effects of CP manifest differently throughout the lifespan. The aging process must inevitably interact with the motor disorder, but we lack systematic, large‐scale follow‐up studies of children with CP into adulthood and through adulthood with thorough assessments performed over time.In this paper we summarize what is known of the epidemiology of CP throughout the lifespan, beginning with mortality and life expectancy, then survey what is known of functioning, ability, and quality of life of adults with CP. We conclude by describing a framework for future research on CP and aging that is built around the World Health Organization’s International Classification of Functioning, Disability, and Health (ICF) and suggest specific tools and approaches for conducting that research in a sound manner.
Epigenetic gambling and epigenetic drift as an antagonistic pleiotropic mechanism of aging
Authors: Martin George M. 
Published: September 2009

SummaryGenerations of biogerontologists have been puzzled by the marked intraspecific variations in lifespan of their experimental model organisms despite all efforts to control both genotype and environment. The most cogent example comes from life table studies of wild‐type Caenorhabditis elegans when grown in suspension cultures using axenic media. While nuclear and mitochondrial somatic mutations and ‘thermodynamic noise’ likely contribute to such lifespan variegations, I raise an additional hypothetical mechanism, one that may have evolved as a mechanism of phenotypic variation which could have preceded the evolution of meiotic recombination. I suggest that random changes in cellular gene expression (cellular epigenetic gambling or bet hedging) evolved as an adaptive mechanism to ensure survival of members of a group in the face of unpredictable environmental challenges. Once activated, it could lead to progressive epigenetic variegation (epigenetic drift) amongst all members of the group. Thus, while particular patterns of gene expression would be adaptive for a subset of reproductive individuals within a population early in life, once initiated, I predict that continued epigenetic drift will result in variable onsets and patterns of pathophysiology – perhaps yet another example of antagonistic pleiotropic gene action in the genesis of senescent phenotypes. The weakness of this hypothesis is that we do not currently have a plausible molecular mechanism for the putative genetic ‘randomizer’ of epigenetic expression, particularly one whose ‘setting’ may be responsive to the ecology in which a given species evolves. I offer experimental approaches, however, to search for the elusive epigenetic gambler(s).
Calorie restriction effects on silencing and recombination at the yeast rDNA
Authors: Smith Jr Daniel L. , Li Chonghua , Matecic Mirela , Maqani Nazif , Bryk Mary , Smith Jeffrey S. 
Published: September 2009

SummaryAging research has developed rapidly over the past decade, identifying individual genes and molecular mechanisms of the aging process through the use of model organisms and high throughput technologies. Calorie restriction (CR) is the most widely researched environmental manipulation that extends lifespan. Activation of the NAD+‐dependent protein deacetylase Sir2 (Silent Information Regulator 2) has been proposed to mediate the beneficial effects of CR in the budding yeast Saccharomyces cerevisiae, as well as other organisms. Here, we show that in contrast to previous reports, Sir2 is not stimulated by CR to strengthen silencing of multiple reporter genes in the rDNA of S. cerevisiae. CR does modestly reduce the frequency of rDNA recombination, although in a SIR2‐independent manner. CR‐mediated repression of rDNA recombination also does not correlate with the silencing of Pol II‐transcribed noncoding RNAs derived from the rDNA intergenic spacer, suggesting that additional silencing‐independent pathways function in lifespan regulation.
Relative roles of TGF‐β1 and Wnt in the systemic regulation and aging of satellite cell responses
Authors: Carlson Morgan E. , Conboy Michael J. , Hsu Michael , Barchas Laurel , Jeong Jaemin , Agrawal Anshu , Mikels Amanda J. , Agrawal Smita , Schaffer David V. , Conboy Irina M. 
Published: September 2009

SummaryMuscle stem (satellite) cells are relatively resistant to cell‐autonomous aging. Instead, their endogenous signaling profile and regenerative capacity is strongly influenced by the aged P‐Smad3, differentiated niche, and by the aged circulation. With respect to muscle fibers, we previously established that a shift from active Notch to excessive transforming growth factor‐beta (TGF‐β) induces CDK inhibitors in satellite cells, thereby interfering with productive myogenic responses. In contrast, the systemic inhibitor of muscle repair, elevated in old sera, was suggested to be Wnt. Here, we examined the age‐dependent myogenic activity of sera TGF‐β1, and its potential cross‐talk with systemic Wnt. We found that sera TGF‐β1 becomes elevated within aged humans and mice, while systemic Wnt remained undetectable in these species. Wnt also failed to inhibit satellite cell myogenicity, while TGF‐β1 suppressed regenerative potential in a biphasic fashion. Intriguingly, young levels of TGF‐β1 were inhibitory and young sera suppressed myogenesis if TGF‐β1 was activated. Our data suggest that platelet‐derived sera TGF‐β1 levels, or endocrine TGF‐β1 levels, do not explain the age‐dependent inhibition of muscle regeneration by this cytokine. In vivo, TGF‐β neutralizing antibody, or a soluble decoy, failed to reduce systemic TGF‐β1 and rescue myogenesis in old mice. However, muscle regeneration was improved by the systemic delivery of a TGF‐β receptor kinase inhibitor, which attenuated TGF‐β signaling in skeletal muscle. Summarily, these findings argue against the endocrine path of a TGF‐β1‐dependent block on muscle regeneration, identify physiological modalities of age‐imposed changes in TGF‐β1, and introduce new therapeutic strategies for the broad restoration of aged organ repair.
The efficiency of mitochondrial electron transport chain is increased in the long‐lived mrg19 Saccharomyces cerevisiae
Authors: Mittal Nitish , Babu M. Madan , Roy Nilanjan 
Published: September 2009

SummaryIntegrity of mitochondrial functionality is a key determinant of longevity in several organisms. In particular, reduced mitochondrial ROS (mtROS) production leading to decreased mtDNA damage is believed to be a crucial aspect of longevity. The generation of low mtROS was thought to be due to low mitochondrial oxygen consumption. However, recent studies have shown that higher mitochondrial oxygen consumption could still result in low mtROS and contribute to longevity. This increased mitochondrial efficiency (i.e. low mtROS generated despite high oxygen consumption) was explained as a result of mitochondrial biogenesis, which provides more entry points for the electrons to the electron transport chain (ETC), thereby resulting in low mtROS production. In this study, we provide evidence for the existence of an alternative pathway to explain the observed higher mitochondrial efficiency in the long‐lived mrg19 mutant of Saccharomyces cerevisiae. Although we observe similar amounts of mitochondria in mrg19 and wild‐type (wt) yeast, we find that mrg19 mitochondria have higher expression of ETC components per mitochondria in comparison with the wt. These findings demonstrate that more efficient mitochondria because of increased ETC per mitochondria can also produce less mtROS. Taken together, our findings provide evidence for an alternative explanation for the involvement of higher mitochondrial activity in prolonging lifespan. We anticipate that similar mechanisms might also exist in eukaryotes including human.
Constitutional Anomie: Patterns of Democracy and ‘The Governance of Britain’
Authors: Flinders Matthew 
Published: September 2009

Abstract‘The Governance of Britain’ agenda represents Gordon Brown's attempt to respond to long-standing criticisms regarding the way in which Labour governments have since 1997 approached the topic of constitutional reform and democratic renewal. The central argument of this article is that the Labour Party remains afflicted by constitutional anomie and these recent documents, combined with the behaviour of politicians, have done little in response. This article is of methodological importance because it assesses the cumulative impact of recent reforms through the application of Lijphart's framework and reflects on the utility of this tool. It is of conceptual importance because the results of the systematic analysis add further weight to the accusation of constitutional anomie while also allowing the development of a new conceptual tool – bi-constitutionality – which offers a way of understanding long-standing debates. The article is of normative importance because it avoids the descriptive-prescriptive approach to constitutional literature that has dominated British political studies, and it is relevant for comparative politics because it replicates and takes forward a methodology that has been applied around the world. In doing so it provides a critical case of executive politics and statecraft vis-à-vis constitutional reform.
New Modes of Political Participation and Singapore's Nominated Members of Parliament
Authors: Rodan Garry 
Published: September 2009

AbstractDespite growing recognition that authoritarianism can be far more durable than transition theorists previously expected, transition theory assumptions continue to constrain attempts to understand authoritarian regimes. In particular, alternative avenues of political participation to opposition political parties and electoral contests are under examined. Singapore's authoritarian regime involves a range of such innovative institutional and ideological initiatives, one of the most significant being the Nominated Members of Parliament scheme. This promotes notions of representation different from democratic parliamentary representation that are not without appeal to targeted, emerging social forces. Singapore's political economy dynamics contribute to this responsiveness by obstructing independent power bases.
The haplotype of the MxA gene promoter is associated with hepatitis B virus infection in a Chinese population
Authors: Cao Bangwei , Liu Xing , Hou Fang , Li Wende , Han Zhonggang , Zhang Qipeng , Dai Yue , Xu Changqing , Qi Huimin 
Published: September 2009

AbstractBackground/Aim: The Myxovirus resistance protein A gene (MxA) is a key component of the innate antiviral response and has previously been shown to inhibit several viruses. This study was designed to assess whether the haplotype in the MxA promoter region was associated with hepatitis B virus (HBV) infection in a Chinese population.Methods: Three hundred and twelve HBV‐infected patients and 317 healthy volunteers were enrolled in this study. Two polymorphisms of −88 and −123 located in the MxA gene promoter were identified by the polymerase chain reaction‐restriction fragment length polymorphism method.Results: The individual possessing haplotype GA, which was constructed by the two polymorphisms of −88G and −123A in the MxA gene promoter, was significantly associated with HBV infection [possessing one copy odds ratio (OR)=1.69, 95% confidence interval (CI) 1.21–2.35; two copy OR=2.84, 95% CI 1.12–7.21 respectively].Conclusions: This case–control study suggested that the haplotype GA in the MxA gene promoter region would increase the susceptibility to HBV infection in a Chinese population.
Food intake increases liver stiffness in patients with chronic or resolved hepatitis C virus infection
Authors: Mederacke Ingmar , Wursthorn Karsten , Kirschner Janina , Rifai Kinan , Manns Michael P. , Wedemeyer Heiner , Bahr Matthias J. 
Published: September 2009

AbstractBackground and aims:  Transient elastography is increasingly being used in patients with chronic liver disease. It has proven particularly useful to identify patients with advanced fibrosis or cirrhosis, while classification of no or little fibrosis appears to be difficult. In general, stiffness values <6 kPa are considered normal, whereas patients with higher levels are candidates for a disease‐specific treatment or further diagnostic evaluation. Parameters influencing liver stiffness may include food intake that increases liver blood flow.Methods:  In a pilot study, transient elastography was performed in eight patients with chronic hepatitis C at fasting and serially for 180 min after intake of a standardized breakfast. Confirmatory, 56 patients and 19 controls underwent liver stiffness determination at fasting, directly after meal intake and 1 h after breakfast.Results:  Liver stiffness significantly increased immediately after food intake for up to 60 min (P=0.01) before normalizing after 180 min. An intraindividual analysis showed a significant increase in 22 out of 43 patients with an initial liver stiffness ≤10 kPa. An increase of at least 1 kPa after food intake was found in 24 out of 43 (56%) patients with initial stiffness ≤10 kPa. Notably, nine out of 23 (39%) patients with normal initial liver stiffness (<6 kPa) had a value of >6 kPa after food intake, potentially leading to unnecessary treatment or diagnostic procedures.Conclusion:  Food intake increases liver stiffness in patients with hepatitis C virus infection and healthy controls. To standardize liver stiffness evaluation, we suggest measurement in the fasting condition.
Flufenamic acid suppresses epileptiform activity in hippocampus by reducing excitatory synaptic transmission and neuronal excitability
Authors: Fernández Miriam , Lao‐Peregrín Cristina , Martín Eduardo D. 
Published: September 2009

SummaryPurpose: In this study, we explore the antiepileptic effects of flufenamic acid (FFA) in order to identify the cellular mechanisms that underlie the potential anticonvulsant properties of this nonsteroidal antiinflammatory compound.Methods: The mechanisms of FFA action were analyzed using an in vitro model in which epileptiform activity was induced in hippocampal slices by perfusion with 100 μm4‐aminopyridine (4‐AP) added to a modified Mg2+‐free solution. The activity of CA1 pyramidal neurons as well as the synaptic connection between CA3 and CA1 was monitored using extracellular and patch‐clamp recordings.Results: Epileptiform activity was suppressed in hippocampal neurons by FFA at concentrations between 50 and 200 μm. Glutamatergic excitatory synaptic transmission was diminished by FFA without modifying recurrent γ‐aminobutyric acid (GABA)ergic synaptic inhibition. Several lines of evidence indicated that FFA did not decrease neurotransmitter release probability, implicating a postsynaptic mechanism of action. FFA also potently reduced neuronal excitability, but did not alter the amplitude, duration, or undershoot of action potentials.Conclusions: Our results suggest that FFA exerts an anticonvulsive effect on hippocampal pyramidal neurons by simultaneously decreasing glutamatergic excitatory synaptic activity and reducing neuronal excitability. Therefore, our study provides experimental evidence that FFA may represent an effective pharmacologic agent in the treatment of epilepsy in the mammalian central nervous system.
Lengthening of corrected QT during epileptic seizures
Authors: Brotherstone Ruth , Blackhall Bethia , McLellan Ailsa 
Published: September 2009

SummaryPurpose: To measure the corrected QT cardiac repolarization time before and during epileptic seizures.Methods: Thirty‐nine video‐EEG/ECG/SAO2(electroencephalography/electrocardiography/oxygen saturation) telemetry patients were included in this prospective study. Epileptic seizures were identified both clinically and electrographically. RR intervals and associated QT intervals were measured 5 min prior to the onset of the identified seizure. Consecutive RR and associated QT intervals were then measured from the seizure onset until the seizure had ended and the EEG had resumed its preseizure trace. Averaged RR and QT intervals over nine consecutive beats were applied to Bazett’s, Hodge’s, Fridericia’s, and Framingham’s formulas to compare the corrected QT values before and during the seizures.Results: A total of 156 seizures had corrected QT analysis performed. Nine generalized tonic–clonic seizures (5 patients), 34 absences (6 patients), 12 tonic seizures (6 patients), 27 temporal lobe seizures (14 patients), 58 frontal lobe seizures (4 patients), and 16 subclinical seizures (4 patients). All formulae reported a statistically significant difference in corrected QT (p < 0.001) during total seizure data compared to total preseizure values. According to Bazett’s formula, 21 seizures (nine patients) transiently increased their corrected QT beyond normal limits, with a maximum corrected QT of 512 ms during a right temporal lobe seizure.Conclusion: Significant lengthening of corrected QT cardiac repolarization time occurred during some epileptic seizures in this study. Prolonged corrected QT may have a role in sudden unexplained death in epilepsy (SUDEP).
Recommendation for a definition of acute symptomatic seizure
Authors: Beghi Ettore , Carpio Arturo , Forsgren Lars , Hesdorffer Dale C. , Malmgren Kristina , Sander Josemir W. , Tomson Torbjorn , Hauser W. Allen 
Published: September 2009

SummaryPurpose:  To consider the definition of acute symptomatic seizures for epidemiological studies, and to refine the criteria used to distinguish these seizures from unprovoked seizures for specific etiologies.Methods:  Systematic review of the literature and of epidemiologic studies.Results:  An acute symptomatic seizure is defined as a clinical seizure occurring at the time of a systemic insult or in close temporal association with a documented brain insult. Suggestions are made to define acute symptomatic seizures as those events occurring within 1 week of stroke, traumatic brain injury, anoxic encephalopathy, or intracranial surgery; at first identification of subdural hematoma; at the presence of an active central nervous system (CNS) infection; or during an active phase of multiple sclerosis or other autoimmune diseases. In addition, a diagnosis of acute symptomatic seizure should be made in the presence of severe metabolic derangements (documented within 24 h by specific biochemical or hematologic abnormalities), drug or alcohol intoxication and withdrawal, or exposure to well‐defined epileptogenic drugs.Discussion:  Acute symptomatic seizures must be distinguished from unprovoked seizures and separately categorized for epidemiologic purposes. These recommendations are based upon the best available data at the time of this report. Systematic studies should be undertaken to better define the associations in question, with special reference to metabolic and toxic insults, for which the time window for the occurrence of an acute symptomatic seizure and the absolute values for toxic and metabolic dysfunction still require a clear identification.