Microbial ecology of a shallow alkaline hydrothermal vent: Strýtan Hydrothermal Field, Eyjafördur, northern Iceland.

Strýtan Hydrothermal Field (SHF) is a submarine system located in Eyjafördur in northern Iceland composed of two main vents: Big Strýtan and Arnarnesstrýtan. The vents are shallow, ranging from 16 to 70 m water depth, and vent high pH (up to 10.2), moderate temperature (T max ∼70°C), anoxic, fresh fluids elevated in dissolved silica, with slightly elevated concentrations of hydrogen and methane. In contrast to other alkaline hydrothermal vents, SHF is unique because it is hosted in basalt and therefore the high pH is not created by serpentinization. While previous studies have assessed the geology and geochemistry of this site, the microbial diversity of SHF has not been explored in detail. Here we present a microbial diversity survey of the actively venting fluids and chimneys from Big Strýtan and Arnarnesstrýtan, using 16S rRNA gene amplicon sequencing. Community members from the vent fluids are mostly aerobic heterotrophic bacteria; however, within the chimneys oxic, low oxygen, and anoxic habitats could be distinguished, where taxa putatively capable of acetogenesis, sulfur-cycling, and hydrogen metabolism were observed. Very few archaea were observed in the samples. The inhabitants of SHF are more similar to terrestrial hot spring samples than other marine sites. It has been hypothesized that life on Earth (and elsewhere in the solar system) could have originated in an alkaline hydrothermal system, however all other studied alkaline submarine hydrothermal systems to date are fueled by serpentinization. SHF adds to our understandings of hydrothermal vents in relationship to microbial diversity, evolution, and possibly the origin of life.

Phototrophy and carbon fixation in Chlorobi postdate the rise of oxygen.

While most productivity on the surface of the Earth today is fueled by oxygenic photosynthesis, for much of Earth history it is thought that anoxygenic photosynthesis-using compounds like ferrous iron or sulfide as electron donors-drove most global carbon fixation. Anoxygenic photosynthesis is still performed by diverse bacteria in niche environments today. Of these, the Chlorobi (formerly green sulfur bacteria) are often interpreted as being particularly ancient and are frequently proposed to have fueled the biosphere during late Archean and early Paleoproterozoic time before the rise of oxygenic photosynthesis. Here, we perform comparative genomic, phylogenetic, and molecular clock analyses to determine the antiquity of the Chlorobi and their characteristic phenotypes. We show that contrary to common assumptions, the Chlorobi clade is relatively young, with anoxygenic phototrophy, carbon fixation via the rTCA pathway, and iron oxidation all significantly postdating the rise of oxygen ~2.3 billion years ago. The Chlorobi therefore could not have fueled the Archean biosphere, but instead represent a relatively young radiation of organisms which likely acquired the capacity for anoxygenic photosynthesis and other traits via horizontal gene transfer sometime after the evolution of oxygenic Cyanobacteria.

Sickle cell bone disease and response to intravenous bisphosphonates in children.

Children with sickle cell disease (SCD) have the potential for extensive and early-onset bone morbidity. This study reports on the diversity of bone morbidity seen in children with SCD followed at three tertiary centers. IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications. INTRODUCTION: To evaluate bone morbidity and the response to intravenous (IV) bisphosphonate therapy in children with SCD. METHODS: We conducted a retrospective review of patient records from 2003 to 2019 at three Canadian pediatric tertiary care centers. Radiographs, magnetic resonance images, and computed tomography scans were reviewed for the presence of avascular necrosis (AVN), bone infarcts, and myositis. IV bisphosphonates were offered for bone pain management. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA). RESULTS: Forty-six children (20 girls, 43%) had bone morbidity at a mean age of 11.8 years (SD 3.9) including AVN of the femoral (17/46, 37%) and humeral (8/46, 17%) heads, H-shaped vertebral body deformities due to endplate infarcts (35/46, 76%), and non-vertebral body skeletal infarcts (15/46, 32%). Five children (5/26, 19%) had myositis overlying areas of AVN or bone infarcts visualized on magnetic resonance imaging. Twenty-three children (8/23 girls) received IV bisphosphonate therapy. They all reported significant or complete resolution of bone pain. There were no reports of sickle cell hemolytic crises, pain crises, or stroke attributed to IV bisphosphonate therapy. CONCLUSION: Children with SCD have the potential for extensive and early-onset bone morbidity. In this series, IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications.

Risk of anticholinergic burden in adults with intellectual disabilities: a Scottish retrospective cohort study of n = 17 220.

BACKGROUND: Several drugs have anticholinergic side effects that are associated with adverse health outcomes. Anticholinergic burden studies in adults with intellectual disabilities (ID) have focused exclusively on older adults. This study investigates anticholinergic burden and its associations in adults with ID of all ages (17-94 years). METHODS: Adults with ID (n = 4 305), each with three general population age-sex-neighbourhood-matched controls (n = 12 915), were linked to their prescribed medications with anticholinergic effects between 2009 and 2017. Analyses were undertaken using logistic regression models. RESULTS: Adults with ID were more likely to be prescribed any anticholinergic medicines, odds ratio (OR) = 1.49 (1.38-1.59), especially 'very strong' risk medicines, OR = 2.59 (2.39-2.81); 48.5% had very high total anticholinergic burden (3+) compared with 35.4% of the general population, OR = 1.77 (1.64-1.90). This group difference was greater for males, OR = 2.02 (1.84-2.22), than females, OR = 1.48 (1.33-1.65). Adults with ID had significantly higher odds of having very high total anticholinergic burden up to 75 years old, with the greatest group effect occurring in younger ages, 17-24-year-olds, OR = 3.05 (2.39-3.89), and the extent of the difference decreased as age increased. The main effect of neighbourhood deprivation showed greater group differences with increasing affluence of neighbourhood. Results examining only the ID group showed that very high total anticholinergic burden was greatest for females, OR = 1.21 (1.07-1.37), and those over age 55, and extent of neighbourhood deprivation was not significant. CONCLUSIONS: Adults with ID are at higher risk of anticholinergic burden than the general population, especially young adults. Overall anticholinergic burden increased with age, but burden was high across all ages in the ID group. Very high total anticholinergic burden is prevalent across all types of neighbourhoods for the adults with ID, in contrast to the steeper gradient seen in the general population. Adults with ID have increased likelihood of unintended adverse effects, regardless of potential confounds, so clinicians undertaking medication reviews need to consider anticholinergic side effects and cumulative burden across concomitant medications, including in young adults with ID, not just older adults, and particularly women.

Inter-domain horizontal gene transfer of nickel-binding superoxide dismutase.

The ability of aerobic microorganisms to regulate internal and external concentrations of the reactive oxygen species (ROS) superoxide directly influences the health and viability of cells. Superoxide dismutases (SODs) are the primary regulatory enzymes that are used by microorganisms to degrade superoxide. SOD is not one, but three separate, non-homologous enzymes that perform the same function. Thus, the evolutionary history of genes encoding for different SOD enzymes is one of convergent evolution, which reflects environmental selection brought about by an oxygenated atmosphere, changes in metal availability, and opportunistic horizontal gene transfer (HGT). In this study, we examine the phylogenetic history of the protein sequence encoding for the nickel-binding metalloform of the SOD enzyme (SodN). The genomic potential to produce SodN is widespread among bacteria, including Actinobacteriota (Actinobacteria), Chloroflexota (Chloroflexi), Cyanobacteria, Proteobacteria, Patescibacteria, and others. The gene is also present in many archaea, with Thermoplasmatota and Nanoarchaeota representing the vast majority of archaeal sodN diversity. A comparison of organismal and SodN protein phylogenetic trees reveals several instances of HGT, including multiple inter-domain transfers of the sodN gene from the bacterial domain to the archaeal domain. Nearly half of the archaeal members with sodN live in the photic zone of the marine water column. The sodN gene is widespread and characterized by apparent vertical gene transfer in some sediment- or soil-associated lineages within the Actinobacteriota and Chloroflexota phyla, suggesting the ancestral sodN likely originated in one of these clades before expanding its taxonomic and biogeographic distribution to additional microbial groups in the surface ocean in response to decreasing iron availability. In addition to decreasing iron quotas, nickel-binding SOD has the added benefit of withstanding high reactant and product ROS concentrations without damaging the enzyme, making it particularly well suited for the modern surface ocean.

Phanerozoic radiation of ammonia oxidizing bacteria.

The modern nitrogen cycle consists of a web of microbially mediated redox transformations. Among the most crucial reactions in this cycle is the oxidation of ammonia to nitrite, an obligately aerobic process performed by a limited number of lineages of bacteria (AOB) and archaea (AOA). As this process has an absolute requirement for O2, the timing of its evolution-especially as it relates to the Great Oxygenation Event ~ 2.3 billion years ago-remains contested and is pivotal to our understanding of nutrient cycles. To estimate the antiquity of bacterial ammonia oxidation, we performed phylogenetic and molecular clock analyses of AOB. Surprisingly, bacterial ammonia oxidation appears quite young, with crown group clades having originated during Neoproterozoic time (or later) with major radiations occurring during Paleozoic time. These results place the evolution of AOB broadly coincident with the pervasive oxygenation of the deep ocean. The late evolution AOB challenges earlier interpretations of the ancient nitrogen isotope record, predicts a more substantial role for AOA during Precambrian time, and may have implications for understanding of the size and structure of the biogeochemical nitrogen cycle through geologic time.

Dental attendance, restoration and extractions in adults with intellectual disabilities compared with the general population: a record linkage study.

BACKGROUND: Oral health may be poorer in adults with intellectual disabilities (IDs) who rely on carer support and medications with increased dental risks. METHODS: Record linkage study of dental outcomes, and associations with anticholinergic (e.g. antipsychotics) and sugar-containing liquid medication, in adults with IDs compared with age-sex-neighbourhood deprivation-matched general population controls. RESULTS: A total of 2933/4305 (68.1%) with IDs and 7761/12 915 (60.1%) without IDs attended dental care: odds ratio (OR) = 1.42 [1.32, 1.53]; 1359 (31.6%) with IDs versus 5233 (40.5%) without IDs had restorations: OR = 0.68 [0.63, 0.73]; and 567 (13.2%) with IDs versus 2048 (15.9%) without IDs had dental extractions: OR = 0.80 [0.73, 0.89]. Group differences for attendance were greatest in younger ages, and restoration/extractions differences were greatest in older ages. Adults with IDs were more likely prescribed with anticholinergics (2493 (57.9%) vs. 6235 (48.3%): OR = 1.49 [1.39, 1.59]) and sugar-containing liquids (1641 (38.1%) vs. 2315 (17.9%): OR = 2.89 [2.67, 3.12]). CONCLUSION: Carers support dental appointments, but dentists may be less likely to restore teeth, possibly extracting multiple teeth at individual appointments instead.

Rapidly forming, slowly evolving, spatial patterns from quasi-cycle Mexican Hat coupling.

Alattice-indexed familyof stochasticprocesses hasquasi-cycle oscillationsif itsotherwise-damped oscillations are sustained by noise. Such a family performs the reaction part of a discrete stochastic reaction-diffusion system when we insert a local Mexican Hat-type, difference of Gaussians, coupling on a one-dimensional and on a two-dimensional lattice. Quasi-cycles are a proposed mech-anism for the production of neural oscillations, and Mexican Hat coupling is ubiquitous in the brain. Thus this combination might provide insight into the function of neural oscillations in the brain. Im-portantly, we study this system only in the transient case, on time intervals before saturation occurs. In one dimension, for weak coupling, we find that the phases of the coupled quasi-cycles synchronize (es-tablish a relatively constant relationship, or phase lock) rapidly at coupling strengths lower than those required to produce spatial patterns of their amplitudes. In two dimensions the amplitude patterns form more quickly, but there remain parameter regimes in which phase synchronization patterns form with-out being accompanied by clear amplitude patterns. At higher coupling strengths we find patterns both of phase synchronization and of amplitude (resembling Turing patterns) corresponding to the patterns of phase synchronization. Specific properties of these patterns are controlled by the parameters of the reaction and of the Mexican Hat coupling.

Oral health of adults with intellectual disabilities: a systematic review.

BACKGROUND: There have been several past reports that adults with intellectual disabilities experience poor oral health (tooth loss, periodontal health and untreated dental caries). Loss of a functional dentition has serious consequences, including problems with chewing, swallowing, nutrition, speech, temporomandibular joint osteoarthritis and pain and systemic health conditions. Poor oral health is largely preventable through proactive oral care support. In recent years, social care provision for adults has changed, with deinstitutionalisation and home-based personalised care now being the typical provision in high income countries. Hence, oral health inequalities might be reducing. However, there is limited recent evidence-synthesis on the topic. We aimed to address this. METHOD: PROSPERO registration number: CRD42018089880. We conducted a preferred reporting items for systematic reviews and meta-analyses systematic review of publications since 2008. Four databases were searched with a clear search strategy, strict inclusion criteria for selection of papers, double scoring (two raters), systematic data extraction and quality appraisal of included papers. RESULTS: A total of 33/3958 retrieved articles were included, of which 14 were drawn from dental service users and 10 from Special Olympic athletes, therefore not necessarily being representative of the wider population with intellectual disabilities. Despite this limitation, adults with intellectual disabilities were still shown to experience poor oral health. High levels of poor oral hygiene and gingivitis were found, with many also affected by periodontitis and untreated dental decay. There is clear unmet need relating to both periodontal (gum) and tooth health, leading to tooth loss. CONCLUSIONS: Despite reports in the past of poor oral health amongst adults with intellectual disabilities, and despite it being preventable, there remains a high burden of poor oral health. This highlights the need to raise awareness, and for polices on effective daily oral care, and appropriate service provision. The importance of oral health and its possible negative sequelae needs to be elevated amongst carers and professionals.

Draft Genome Sequences of Two Basal Members of the Anaerolineae Class of Chloroflexi from a Sulfidic Hot Spring.

Here, we describe the first genome sequences of the Anaerolineae from a sulfidic environment, expanding the environmental distribution of sequenced Anaerolineae These genomes represent basal Anaerolineae lineages, branching soon after the divergence of the sister class "Candidatus Thermofonsia," expanding our understanding of the metabolic evolution of this group.

Draft Genome Sequence of a Divergent Anaerobic Member of the Chloroflexi Class Ardenticatenia from a Sulfidic Hot Spring.

Here, we present a draft genome sequence of Nak82, the second genome sequence available for the Chloroflexi class Ardenticatenia and the first from a sulfidic terrestrial hot spring. Nak82 is genetically and metabolically distinct from Ardenticatena maritima and likely represents a new genus- or family-level lineage lacking high-potential respiratory pathways.

Automated DXA-based finite element analysis for hip fracture risk stratification: a cross-sectional study.

Fracture risk indices (FRIs) generated from DXA-based finite element analysis were associated with hip fracture independent of FRAX score computed with femoral neck bone mineral density (BMD). Prospective studies are warranted to determine whether FRIs represent an improvement over BMD for predicting incident hip fractures. INTRODUCTION: The study aims to examine the association between prior hip fracture and FRIs derived from automated finite element analysis (FEA) of DXA hip scans. Femoral neck, intertrochanteric, and subtrochanteric FRIs were calculated as the von Mises stress induced by a sideways fall divided by the bone yield stress over the specified region of interest (ROI). METHODS: Using the Manitoba Bone Mineral Density Database, we selected women age ≥ 65 years with femoral neck T-scores below - 1 and no osteoporosis treatment. From this population, we identified 324 older women with hip fracture before DXA testing and a random sample of 658 non-fracture controls. FRIs were derived from the anonymized DXA scans. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between FRIs (per SD increase) and hip fracture. RESULTS: After adjusting for FRAX score (hip fracture with BMD), femoral neck FRI (OR 1.36, 95% CI 1.13, 1.64), intertrochanteric FRI (OR 1.81, 95% CI 1.44, 2.27), and subtrochanteric FRI (OR 2.09, 95% CI 1.68, 2.60) were associated with hip fracture. Intertrochanteric and subtrochanteric FRIs gave significantly higher c-statistics (all P ≤ 0.05) than femoral neck BMD. Subgroup analyses showed that all FRIs were more strongly associated with hip fracture in women who were younger and had higher body mass index (BMI) or non-osteoporotic BMD (all P interaction < 0.1). CONCLUSIONS: FRIs derived from DXA-based FEA were independently associated with prior hip fracture, suggesting that they could potentially improve hip fracture risk assessment.

Microbial diversity and iron oxidation at Okuoku-hachikurou Onsen, a Japanese hot spring analog of Precambrian iron formations.

Banded iron formations (BIFs) are rock deposits common in the Archean and Paleoproterozoic (and regionally Neoproterozoic) sedimentary successions. Multiple hypotheses for their deposition exist, principally invoking the precipitation of iron via the metabolic activities of oxygenic, photoferrotrophic, and/or aerobic iron-oxidizing bacteria. Some isolated environments support chemistry and mineralogy analogous to processes involved in BIF deposition, and their study can aid in untangling the factors that lead to iron precipitation. One such process analog system occurs at Okuoku-hachikurou (OHK) Onsen in Akita Prefecture, Japan. OHK is an iron- and CO2 -rich, circumneutral hot spring that produces a range of precipitated mineral textures containing fine laminae of aragonite and iron oxides that resemble BIF fabrics. Here, we have performed 16S rRNA gene amplicon sequencing of microbial communities across the range of microenvironments in OHK to describe the microbial diversity present and to gain insight into the cycling of iron, oxygen, and carbon in this ecosystem. These analyses suggest that productivity at OHK is based on aerobic iron-oxidizing Gallionellaceae. In contrast to other BIF analog sites, Cyanobacteria, anoxygenic phototrophs, and iron-reducing micro-organisms are present at only low abundances. These observations support a hypothesis where low growth yields and the high stoichiometry of iron oxidized per carbon fixed by aerobic iron-oxidizing chemoautotrophs like Gallionellaceae result in accumulation of iron oxide phases without stoichiometric buildup of organic matter. This system supports little dissimilatory iron reduction, further setting OHK apart from other process analog sites where iron oxidation is primarily driven by phototrophic organisms. This positions OHK as a study area where the controls on primary productivity in iron-rich environments can be further elucidated. When compared with geological data, the metabolisms and mineralogy at OHK are most similar to specific BIF occurrences deposited after the Great Oxygenation Event, and generally discordant with those that accumulated before it.

Musculoskeletal health in newly diagnosed children with Crohn's disease.

We evaluated the impact of Crohn's disease on muscle and bone strength, mass, density, and geometry in children with newly diagnosed CD and found profound muscle and bone deficits; nevertheless, the prevalence of vertebral fractures at this time point was low. INTRODUCTION: Crohn's disease (CD) is an inflammatory condition of the gastrointestinal tract that can affect the musculoskeletal system. The objective of this study was to determine the prevalence of vertebral fractures and the impact of CD on muscle and bone mass, strength, density, and geometry in children with newly diagnosed CD. METHODS: Seventy-three children (26 girls) aged 7.0 to 17.7 years were examined within 35 days following CD diagnosis by lateral spine radiograph for vertebral fractures and by jumping mechanography for muscle strength. Bone and muscle mass, density, and geometry were assessed by dual-energy x-ray absorptiometry and peripheral quantitative computed tomography (pQCT). RESULTS: Disease activity was moderate to severe in 66 (90%) patients. Mean height (Z-score -0.3, standard deviation (SD) 1.1, p = 0.02), weight (Z-score -0.8, SD 1.3, p < 0.01), body mass index (Z-score -1.0, SD 1.3, p < 0.01), lumbar spine areal bone mineral density (BMD; Z-score -1.1, SD 1.0, p < 0.01), total body bone mineral content (Z-score -1.5, SD 1.0, p < 0.01), and total body lean mass (Z-score -2.5, SD 1.1, p < 0.01) were all low for age and gender. pQCT showed reduced trabecular volumetric BMD at the tibial metaphysis, expansion of the bone marrow cavity and thin cortices at the diaphysis, and low calf muscle cross-sectional area. Jumping mechanography demonstrated low muscle power. Only one patient had a vertebral fracture. CONCLUSIONS: Children with newly diagnosed CD have profound muscle and bone deficits; nevertheless, the prevalence of vertebral fractures at this time point was low.

Molecular diagnosis in children with fractures but no extraskeletal signs of osteogenesis imperfecta.

In 26 of 94 individuals (28%) below 21 years of age who had a significant fracture history but did not have extraskeletal features of osteogenesis imperfecta (OI), we detected disease-causing mutations in OI-associated genes. INTRODUCTION: In children who have mild bone fragility but do not have extraskeletal features of OI, it can be difficult to establish a diagnosis on clinical grounds. Here, we assessed the diagnostic yield of genetic testing in this context, by sequencing a panel of genes that are associated with OI. METHODS: DNA sequence analysis was performed on 94 individuals below 21 years of age who had a significant fracture history but had white sclera and no signs of dentinogenesis imperfecta. RESULTS: Disease-causing variants were detected in 28% of individuals and affected 5 different genes. Twelve individuals had mutations in COL1A1 or COL1A2, 8 in LRP5, 4 in BMP1, and 2 in PLS3. CONCLUSIONS: DNA sequence analysis of currently known OI-associated genes identified disease-causing variants in more than a quarter of individuals with a significant fracture history but without extraskeletal manifestations of OI.

Crown group Oxyphotobacteria postdate the rise of oxygen.

The rise of oxygen ca. 2.3 billion years ago (Ga) is the most distinct environmental transition in Earth history. This event was enabled by the evolution of oxygenic photosynthesis in the ancestors of Cyanobacteria. However, long-standing questions concern the evolutionary timing of this metabolism, with conflicting answers spanning more than one billion years. Recently, knowledge of the Cyanobacteria phylum has expanded with the discovery of non-photosynthetic members, including a closely related sister group termed Melainabacteria, with the known oxygenic phototrophs restricted to a clade recently designated Oxyphotobacteria. By integrating genomic data from the Melainabacteria, cross-calibrated Bayesian relaxed molecular clock analyses show that crown group Oxyphotobacteria evolved ca. 2.0 billion years ago (Ga), well after the rise of atmospheric dioxygen. We further estimate the divergence between Oxyphotobacteria and Melainabacteria ca. 2.5-2.6 Ga, which-if oxygenic photosynthesis is an evolutionary synapomorphy of the Oxyphotobacteria-marks an upper limit for the origin of oxygenic photosynthesis. Together, these results are consistent with the hypothesis that oxygenic photosynthesis evolved relatively close in time to the rise of oxygen.

Unified principles of thalamo-cortical processing: the neural switch.

It has been reported that cross-frequency interactions may play an important role in local processing within thalamus and neocortex, as well as information transfer between subcortical and cortico-cortical brain regions. Strong commonalities in rhythmic network properties have been observed across recording techniques and task demands, but strong neuroscientific theories to situate such observations within a unified framework with direct relevance to explain neuropathologies remain scarce. Based on a comprehensive review of animal and human literature, we probe and introduce a neurophysiological framework to explain how coordinated cross-frequency and interregional oscillatory cortical dynamics underlie typical and atypical brain activation, and the formation of distributed functional ensembles supporting cortical networks underpinning perception and cognition. We propose that local regional activation by an external stimulus via a sensory pathway entails (1) attenuated alpha (8-14 Hz) and increased theta (4-8 Hz) and gamma (30-50 Hz) oscillatory activity, and (2) increased interactions among theta and gamma rhythms. These local dynamics also mediate the integration of activated neural populations into large-scale functional assemblies through neuronal synchronization. This comprehensive perspective into the animal and human literature indicates a further thinking beyond synchrony and connectivity and the readiness for more hypothesis-driven research and modeling toward unified principles of thalamo-cortical processing. We further introduced such a possible framework: "The ATG switch". We also discussed evidence that alpha-theta-gamma dynamics emerging from thalamocortical interactions may be implicated and disrupted in numerous neurological and neuropsychiatric conditions.

The time to and determinants of first fractures in boys with Duchenne muscular dystrophy.

Boys with vertebral fractures (VF) identified through routine spine radiographs had milder, less symptomatic, and fewer VF compared to those diagnosed with VF following consultation for back pain. Spontaneous (i.e., medication-unassisted) reshaping of fractured vertebral bodies was absent. Long bone fractures were present even before Duchenne muscular dystrophy (DMD) diagnosis in some boys. INTRODUCTION: The objective of the study was to determine the time to and characteristics of first fractures in Duchenne muscular dystrophy. METHODS: This study was a retrospective longitudinal study of 30 boys with DMD <18 years. Boys were classified into four groups according to their first fracture: those with VF identified on routine lateral spine radiographs, those with VF diagnosed following consultation for back pain, those with long bone fractures, and those without fractures. RESULTS: Compared to boys diagnosed with VF as their initial fracture following consultation for back pain, those with VF surveillance radiographs had shorter durations of glucocorticoid (GC) therapy at the time of VF diagnosis (median 1.6 versus 5.3 years, p < 0.01), higher areal (mean ± standard deviation -1.4 ± 0.7 versus -3.1 ± 0.8, p = 0.01), and volumetric (-0.3 ± 0.5 versus -2.6 ± 0.8, p < 0.01) lumbar spine bone mineral density Z-scores, as well as fewer VF (median 1.4 versus 5.2 per person, p < 0.01) and a lower median spinal deformity index (median 1.5 versus 9.5, p < 0.01). Vertebral body reshaping following VF was not observed. Ten boys sustained a long bone fracture as their first fracture at a mean age of 8.9 ± 4.0 years; four of these boys later sustained a total of 27 incident VF. CONCLUSIONS: Routine lateral spine radiographs led to detection of VF in their earlier stages, vertebral body reshaping following VF was absent, and VF were frequent after the first long bone fracture. These results support the inclusion of a lateral spine radiograph starting at the time of GC initiation as part of routine bone health monitoring in DMD.

The management of osteoporosis in children.

This article reviews the manifestations and risk factors associated with osteoporosis in childhood, the definition of osteoporosis and recommendations for monitoring and prevention. As well, this article discusses when a child should be considered a candidate for osteoporosis therapy, which agents should be prescribed, duration of therapy and side effects. There has been significant progress in our understanding of risk factors and the natural history of osteoporosis in children over the past number of years. This knowledge has fostered the development of logical approaches to the diagnosis, monitoring, and optimal timing of osteoporosis intervention in this setting. Current management strategies are predicated upon monitoring at-risk children to identify and then treat earlier rather than later signs of osteoporosis in those with limited potential for spontaneous recovery. On the other hand, trials addressing the prevention of the first-ever fracture are still needed for children who have both a high likelihood of developing fractures and less potential for recovery. This review focuses on the evidence that shapes the current approach to diagnosis, monitoring, and treatment of osteoporosis in childhood, with emphasis on the key pediatric-specific biological principles that are pivotal to the overall approach and on the main questions with which clinicians struggle on a daily basis. The scope of this article is to review the manifestations of and risk factors for primary and secondary osteoporosis in children, to discuss the definition of pediatric osteoporosis, and to summarize recommendations for monitoring and prevention of bone fragility. As well, this article reviews when a child is a candidate for osteoporosis therapy, which agents and doses should be prescribed, the duration of therapy, how the response to therapy is adjudicated, and the short- and long-term side effects. With this information, the bone health clinician will be poised to diagnose osteoporosis in children and to identify when children need osteoporosis therapy and the clinical outcomes that gauge efficacy and safety of treatment.

Automatic determination of EMG-contaminated components and validation of independent component analysis using EEG during pharmacologic paralysis.

OBJECTIVE: Validate independent component analysis (ICA) for removal of EMG contamination from EEG, and demonstrate a heuristic, based on the gradient of EEG spectra (slope of graph of log EEG power vs log frequency, 7-70 Hz) from paralysed awake humans, to automatically identify and remove components that are predominantly EMG. METHODS: We studied the gradient of EMG-free EEG spectra to quantitatively inform the choice of threshold. Then, pre-existing EEG from 3 disparate experimental groups was examined before and after applying the heuristic to validate that the heuristic preserved neurogenic activity (Berger effect, auditory odd ball, visual and auditory steady state responses). RESULTS: (1) ICA-based EMG removal diminished EMG contamination up to approximately 50 Hz, (2) residual EMG contamination using automatic selection was similar to manual selection, and (3) task-induced cortical activity remained, was enhanced, or was revealed using the ICA-based methodology. CONCLUSION: This study further validates ICA as a powerful technique for separating and removing myogenic signals from EEG. Automatic processing based on spectral gradients to exclude EMG-containing components is a conceptually simple and valid technique. SIGNIFICANCE: This study strengthens ICA as a technique to remove EMG contamination from EEG whilst preserving neurogenic activity to 50 Hz.