Neurologic Correlates of Gait Abnormalities in Cerebral Palsy: Implications for Treatment

Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children. Neuroimaging of high-risk neonates and of children diagnosed with CP have identified patterns of neurologic injury associated with CP, however, the neural underpinnings of common gait abnormalities remain largely uncharacterized. Here, we review the nature of the brain injury in CP, as well as the neuromuscular deficits and subsequent gait abnormalities common among children with CP. We first discuss brain injury in terms of mechanism, pattern, and time of injury during the prenatal, perinatal, or postnatal period in preterm and term-born children. Second, we outline neuromuscular deficits of CP with a focus on spastic CP, characterized by muscle weakness, shortened muscle-tendon unit, spasticity, and impaired selective motor control, on both a microscopic and functional level. Third, we examine the influence of neuromuscular deficits on gait abnormalities in CP, while considering emerging information on neural correlates of gait abnormalities and the implications for strategic treatment. This review of the neural basis of gait abnormalities in CP discusses what is known about links between the location and extent of brain injury and the type and severity of CP, in relation to the associated neuromuscular deficits, and subsequent gait abnormalities. Targeted treatment opportunities are identified that may improve functional outcomes for children with CP. By providing this context on the neural basis of gait abnormalities in CP, we hope to highlight areas of further research that can reduce the long-term, debilitating effects of CP

Evolution of electron transfer out of the cell: comparative genomics of six Geobacter genomes

Background: Geobacter species grow by transferring electrons out of the cell - either to Fe(III)-oxides or to manmade substances like energy-harvesting electrodes. Study of Geobacter sulfurreducens has shown that TCA cycle enzymes, inner-membrane respiratory enzymes, and periplasmic and outer-membrane cytochromes are required. Here we present comparative analysis of six Geobacter genomes, including species from the clade that predominates in the subsurface. Conservation of proteins across the genomes was determined to better understand the evolution of Geobacter species and to create a metabolic model applicable to subsurface environments. Results: The results showed that enzymes for acetate transport and oxidation, and for proton transport across the inner membrane were well conserved. An NADH dehydrogenase, the ATP synthase, and several TCA cycle enzymes were among the best conserved in the genomes. However, most of the cytochromes required for Fe(III)-reduction were not, including many of the outer-membrane cytochromes. While conservation of cytochromes was poor, an abundance and diversity of cytochromes were found in every genome, with duplications apparent in several species. Conclusions: These results indicate there is a common pathway for acetate oxidation and energy generation across the family and in the last common ancestor. They also suggest that while cytochromes are important for extracellular electron transport, the path of electrons across the periplasm and outer membrane is variable. This combination of abundant cytochromes with weak sequence conservation suggests they may not be specific terminal reductases, but rather may be important in their heme-bearing capacity, as sinks for electrons between the inner-membrane electron transport chain and the extracellular acceptor

Evolution from a respiratory ancestor to fill syntrophic and fermentative niches: comparative fenomics of six Geobacteraceae species

<p>Abstract</p> <p>Background</p> <p>The anaerobic degradation of organic matter in natural environments, and the biotechnical use of anaerobes in energy production and remediation of subsurface environments, both require the cooperative activity of a diversity of microorganisms in different metabolic niches. The <it>Geobacteraceae </it>family contains members with three important anaerobic metabolisms: fermentation, syntrophic degradation of fermentation intermediates, and anaerobic respiration.</p> <p>Results</p> <p>In order to learn more about the evolution of anaerobic microbial communities, the genome sequences of six <it>Geobacteraceae </it>species were analyzed. The results indicate that the last common <it>Geobacteraceae </it>ancestor contained sufficient genes for anaerobic respiration, completely oxidizing organic compounds with the reduction of external electron acceptors, features that are still retained in modern <it>Geobacter </it>and <it>Desulfuromonas </it>species. Evolution of specialization for fermentative growth arose twice, via distinct lateral gene transfer events, in <it>Pelobacter carbinolicus </it>and <it>Pelobacter propionicus</it>. Furthermore, <it>P. carbinolicus </it>gained hydrogenase genes and genes for ferredoxin reduction that appear to permit syntrophic growth via hydrogen production. The gain of new physiological capabilities in the <it>Pelobacter </it>species were accompanied by the loss of several key genes necessary for the complete oxidation of organic compounds and the genes for the <it>c</it>-type cytochromes required for extracellular electron transfer.</p> <p>Conclusion</p> <p>The results suggest that <it>Pelobacter </it>species evolved parallel strategies to enhance their ability to compete in environments in which electron acceptors for anaerobic respiration were limiting. More generally, these results demonstrate how relatively few gene changes can dramatically transform metabolic capabilities and expand the range of environments in which microorganisms can compete.</p

Genomic and microarray analysis of aromatics degradation in Geobacter metallireducens and comparison to a Geobacter isolate from a contaminated field site

<p>Abstract</p> <p>Background</p> <p>Groundwater and subsurface environments contaminated with aromatic compounds can be remediated <it>in situ </it>by <it>Geobacter </it>species that couple oxidation of these compounds to reduction of Fe(III)-oxides. <it>Geobacter metallireducens </it>metabolizes many aromatic compounds, but the enzymes involved are not well known.</p> <p>Results</p> <p>The complete <it>G. metallireducens </it>genome contained a 300 kb island predicted to encode enzymes for the degradation of phenol, <it>p</it>-cresol, 4-hydroxybenzaldehyde, 4-hydroxybenzoate, benzyl alcohol, benzaldehyde, and benzoate. Toluene degradation genes were encoded in a separate region. None of these genes was found in closely related species that cannot degrade aromatic compounds. Abundant transposons and phage-like genes in the island suggest mobility, but nucleotide composition and lack of synteny with other species do not suggest a recent transfer. The inferred degradation pathways are similar to those in species that anaerobically oxidize aromatic compounds with nitrate as an electron acceptor. In these pathways the aromatic compounds are converted to benzoyl-CoA and then to 3-hydroxypimelyl-CoA. However, in <it>G. metallireducens </it>there were no genes for the energetically-expensive dearomatizing enzyme. Whole-genome changes in transcript levels were identified in cells oxidizing benzoate. These supported the predicted pathway, identified induced fatty-acid oxidation genes, and identified an apparent shift in the TCA cycle to a putative ATP-yielding succinyl-CoA synthase. Paralogs to several genes in the pathway were also induced, as were several putative molybdo-proteins. Comparison of the aromatics degradation pathway genes to the genome of an isolate from a contaminated field site showed very similar content, and suggested this strain degrades many of the same compounds. This strain also lacked a classical dearomatizing enzyme, but contained two copies of an eight-gene cluster encoding redox proteins that was 30-fold induced during benzoate oxidation.</p> <p>Conclusion</p> <p><it>G. metallireducens </it>appears to convert aromatic compounds to benzoyl-CoA, then to acetyl-CoA via fatty acid oxidation, and then to carbon dioxide via the TCA cycle. The enzyme responsible for dearomatizing the aromatic ring may be novel, and energetic investments at this step may be offset by a change in succinate metabolism. Analysis of a field isolate suggests that the pathways inferred for <it>G. metallireducens </it>may be applicable to modeling <it>in situ </it>bioremediation.</p

KINEMATIC AND KINETIC ANALYSIS OF THE ELITE GOLF SWING

The purpose of this study was to determine the association between select biomechanical variables and clubhead speed at impact (CSI) in a sample of elite golfers. Power generation is thought to arise from a number of factors including body rotation and weight shift. CSI is often used to indicate power generation (Fradkin, et al., 2004). We hypothesized that CSI would be highly related to torque, relative hip-shoulder rotation (X-factor) and weight shift during the golf swing

Travelling and sticky affects: : Exploring teens and sexualized cyberbullying through a Butlerian-Deleuzian- Guattarian lens

In this paper we combine the thinking of Deleuze and Guattari (1984, 1987) with Judith Butler’s (1990, 1993, 2004, 2009) work to follow the rhizomatic becomings of young people’s affective relations in a range of on- and off-line school spaces. In particular we explore how events that may be designated as sexual cyberbullying are constituted and how they are mediated by technology (such as texting or in/through social networking sites). Drawing on findings from two different studies looking at teens’ uses of and experiences with social networking sites, Arto in Denmark, and Bebo in the UK, we use this approach to think about how affects flow, are distributed, and become fixed in assemblages. We map how affects are manoeuvred and potentially disrupted by young people, suggesting that in the incidences discussed affects travel as well as stick in points of fixation. We argue that we need to grasp both affective flow and fixity in order to gain knowledge of how subjectification of the gendered/classed/racialised/sexualised body emerges. A Butlerian-Deleuzian-Guattarian frame helps us to map some of these affective complexities that shape sexualized cyberbully events; and to recognize technologically mediated lines of flight when subjectifications are at least temporarily disrupted and new terms of recognition and intelligibility staked out. Keywords

De Novo Assembly of the Complete Genome of an Enhanced Electricity-Producing Variant of Geobacter sulfurreducens Using Only Short Reads

State-of-the-art DNA sequencing technologies are transforming the life sciences due to their ability to generate nucleotide sequence information with a speed and quantity that is unapproachable with traditional Sanger sequencing. Genome sequencing is a principal application of this technology, where the ultimate goal is the full and complete sequence of the organism of interest. Due to the nature of the raw data produced by these technologies, a full genomic sequence attained without the aid of Sanger sequencing has yet to be demonstrated

Briefing: improving children and young people's mental health services: local data insights from England, Scotland and Wales.

In this briefing, we present analysis from the Networked Data Lab (NDL). Led by the Health Foundation, the NDL is a collaborative network of local analytical teams across England, Scotland and Wales. These teams analysed local, linked data sources to explore trends in mental health presentations across primary, specialist and acute services. This briefing includes: a) background on the trends in mental health disorders among children and young people and existing pressures on services, as well as an overview of the main policies in place in England, Scotland, and Wales to improve children and young people's mental health b) findings from NDL partners: we examine trends and patterns of service use, including the use of primary care, specialist mental health care and acute services, along with differences by demographic and socioeconomic characteristics c) examples of how local NDL teams used linked data to improve services in their area d) insights for national and local policymakers

The clinically extremely vulnerable to COVID: identification and changes in healthcare while self-isolating (shielding) during the coronavirus pandemic.

In March 2020, the government of Scotland identified people deemed clinically extremely vulnerable to COVID due to their pre-existing health conditions. These people were advised to strictly self-isolate (shield) at the start of the pandemic, except for necessary healthcare. We examined who was identified as clinically extremely vulnerable, how their healthcare changed during isolation, and whether this process exacerbated healthcare inequalities. We linked those on the shielding register in NHS Grampian, a health authority in Scotland, to healthcare records from 2015-2020. We described the source of identification, demographics, and clinical history of the cohort. We measured changes in out-patient, in-patient, and emergency healthcare during isolation in the shielding population and compared to the general non-shielding population. The register included 16,092 people (3% of the population), clinically vulnerable primarily due to a respiratory disease, immunosuppression, or cancer. Among them, 42% were not identified by national healthcare record screening but added ad hoc, with these additions including more children and fewer economically-deprived. During isolation, all forms of healthcare use decreased (25%-46%), with larger decreases in scheduled care than in emergency care. However, people shielding had better maintained scheduled care compared to the non-shielding general population: out-patient visits decreased 35% vs 49%; in-patient visits decreased 46% vs 81%. Notably, there was substantial variation in whose scheduled care was maintained during isolation: younger people and those with cancer had significantly higher visit rates, but there was no difference between sexes or socioeconomic levels. Healthcare changed dramatically for the clinically extremely vulnerable population during the pandemic. The increased reliance on emergency care while isolating indicates that continuity of care for existing conditions was not optimal. However, compared to the general population, there was success in maintaining scheduled care, particularly in young people and those with cancer. We suggest that integrating demographic and primary care data would improve identification of the clinically vulnerable and could aid prioritising their care

Serious mental health diagnoses in children on the child protection register: a record linkage study.

Children with experience of maltreatment, abuse or neglect are known to have a higher prevalence of poor mental health. Child Protection Services identify children most at risk of harm and in need of intervention. Mental healthcare usage in this population is not well understood as registration data is not routinely linked to health records. We undertook data linkage to describe the population on the register, their mental healthcare usage and to calculate age- and sex-specific incidence rates of mental health outcomes. We analysed records from the Aberdeen City Council Child Protection Register and for mental health prescribing and referrals to child and adolescent mental health services (CAMHS) for the NHS Grampian region between 1st January 2012 and 31st December 2022. We identified 1,498 individuals with a Child Protection Register registration, of which 70% were successfully matched to health records. 20% of registrations occurred before birth and the median age of registration was 3 years. 10.1% of children with a registration ever received a mental health prescription, 5.1% for treatment of attention deficit hyperactivity disorder and 1.7% for treatment of depression. 18.9% received a referral to specialist outpatient Child and Adolescent Mental Health Services. Age- and sex- standardised incidence rates for mental health prescribing and referrals are higher for children with a child protection registration compared to the general population. Children identified as being at significant risk of harm and involved with child protection services are at greater risk of seeking or receiving professional mental health support than their peers. Clinical services should investigate additional ways to support this population’s mental well-being as a priority. Efforts to reduce the exposure of children to potentially harmful environments at a societal level should also be pursued