Comparative connectomics of the descending and ascending neurons of the Drosophila nervous system: stereotypy and sexual dimorphism.

In most complex nervous systems there is a clear anatomical separation between the nerve cord, which contains most of the final motor outputs necessary for behaviour, and the brain. In insects, the neck connective is both a physical and information bottleneck connecting the brain and the ventral nerve cord (VNC, spinal cord analogue) and comprises diverse populations of descending (DN), ascending (AN) and sensory ascending neurons, which are crucial for sensorimotor signalling and control. Integrating three separate EM datasets, we now provide a complete connectomic description of the ascending and descending neurons of the female nervous system of Drosophila and compare them with neurons of the male nerve cord. Proofread neuronal reconstructions have been matched across hemispheres, datasets and sexes. Crucially, we have also matched 51% of DN cell types to light level data defining specific driver lines as well as classifying all ascending populations. We use these results to reveal the general architecture, tracts, neuropil innervation and connectivity of neck connective neurons. We observe connected chains of descending and ascending neurons spanning the neck, which may subserve motor sequences. We provide a complete description of sexually dimorphic DN and AN populations, with detailed analysis of circuits implicated in sex-related behaviours, including female ovipositor extrusion (DNp13), male courtship (DNa12/aSP22) and song production (AN hemilineage 08B). Our work represents the first EM-level circuit analyses spanning the entire central nervous system of an adult animal.

γ-TuRCs and the augmin complex are required for the development of highly branched dendritic arbors in Drosophila.

Microtubules are nucleated by γ-tubulin ring complexes (γ-TuRCs) and are essential for neuronal development. Nevertheless, γ-TuRC depletion has been reported to perturb only higher-order branching in elaborated Drosophila larval class IV dendritic arborization (da) neurons. This relatively mild phenotype has been attributed to defects in microtubule nucleation from Golgi outposts, yet most Golgi outposts lack associated γ-TuRCs. By analyzing dendritic arbor regrowth in pupae, we show that γ-TuRCs are also required for the growth and branching of primary and secondary dendrites, as well as for higher-order branching. Moreover, we identify the augmin complex (hereafter augmin), which recruits γ-TuRCs to the sides of pre-existing microtubules, as being required predominantly for higher-order branching. Augmin strongly promotes the anterograde growth of microtubules in terminal dendrites and thus terminal dendrite stability. Consistent with a specific role in higher-order branching, we find that augmin is expressed less strongly and is largely dispensable in larval class I da neurons, which exhibit few higher-order dendrites. Thus, γ-TuRCs are essential for various aspects of complex dendritic arbor development, and they appear to function in higher-order branching via the augmin pathway, which promotes the elaboration of dendritic arbors to help define neuronal morphology.

Incidence, Healthcare Resource Use and Costs Associated With Incisional Hernia Repair.

Background: Incisional hernia (IH) is a common complication of abdominal surgery affecting between 12.8% and 30% of patients. In spite of this, rates of IH repair remain low, at around 5% in the literature. We aimed to assess the rate of IH repair in the UK across surgical specialties and the cost burden associated with IH repair. Methods: This is a retrospective observational study of patients undergoing abdominal surgery in England between 2012 and 2022 using the Hospital Episode Statistics (HES) database. Index abdominal surgery was identified between March 2014 and March 2017. Diagnostic and surgical procedure codes were used to identify pre-operative risk factors, index surgeries, IH repair and healthcare contact. Healthcare resource use (HCRU) costs were derived for index surgery and all post-index, non-elective inpatient admissions and outpatient visits using Healthcare Resource Group (HRG) codes within HES. Results: Of 297,134 patients undergoing abdominal surgery, 5.1% (n = 15,138) subsequently underwent incisional hernia repair. By specialty, rates were higher in Colorectal (10.0%), followed by Hepatobiliary (8.2%), Transplant (6.8%), Urological (4.0%), Bariatric (3.5%), Vascular (3.2%) and Gynaecological (2.6%) surgery. Patients undergoing IH repair had more healthcare contacts, longer length of inpatient stays and more A+E visits vs. those with no IH repair post index surgery (83% ≥ 1 A+E visit vs. 69%), as well as higher rates of referral to mental health services (19.8% vs. 11.5%). IH repair was associated with an average HCRU cost of £23,148 compared to £12,321 in patients with no IH repair. Conclusion: Patients undergoing IH repair have a greater morbidity than those not undergoing repair, shown by higher HCRU and more healthcare contacts. Despite this, rates of surgery for IH are low, suggesting that most patients with hernias are not undergoing repair. Emphasis must be placed squarely on primary prevention, rather than cure.

Complexity-functioning relationships differ across different environmental conditions.

Habitat complexity is widely considered an important determinant of biodiversity, and enhancing complexity can play a key role in restoring degraded habitats. However, the effects of habitat complexity on ecosystem functioning - as opposed to biodiversity and community structure - are relatively poorly understood for artificial habitats, which dominate many coastlines. With Greening of Grey Infrastructure (GGI) approaches, or eco-engineering, increasingly being applied around the globe, it is important to understand the effects that modifying habitat complexity has on both biodiversity and ecological functioning in these highly modified habitats. We assessed how manipulating physical (primary substrate) and/or biogenic habitat (bivalves) complexity on intertidal artificial substrata affected filtration rates, net and gross primary productivity (NPP and GPP, respectively) and community respiration (CR) - as well as abundance of filter feeders and macro-algae and habitat use by cryptobenthic fish across six locations in three continents. We manipulated both physical and biogenic complexity using 1) flat or ridged (2.5 cm or 5 cm) settlement tiles that were either 2) unseeded or seeded with oysters or mussels. Across all locations, increasing physical and biogenic complexity (5 cm seeded tiles) had a significant effect on most ecological functioning variables, increasing overall filtration rates and community respiration of the assemblages on tiles but decreasing productivity (both GPP and NPP) across all locations. There were no overall effects of increasing either type of habitat complexity on cryptobenthic fish MaxN, total time in frame or macro-algal cover. Within each location, there were marked differences in the effects of habitat complexity. In Hobart, we found higher filtration, filter feeder biomass and community respiration on 5 cm tiles compared to flat tiles. However, at this location, both macro-algae cover and GPP decreased with increasing physical complexity. Similarly in Dublin, filtration, filter feeder biomass and community respiration were higher on 5 cm tiles compared to less complex tiles. In Sydney, filtration and filter feeder biomass were higher on seeded than unseeded tiles, and fish MaxN was higher on 5 cm tiles compared to flat tiles. On unseeded tiles in Sydney, filter feeder biomass also increased with increasing physical complexity. Our findings suggest that GGI solutions via increased habitat complexity are likely to have trade-offs among potentially desired functions, such as productivity and filtration rates, and variable effects on cryptobenthic fish communities. Importantly, our results show that the effects of GGI practices can vary markedly according to the environmental context and therefore should not be blindly and uniformly applied across the globe.

The influence of environmental context on community composition in artificial rockpools associated with seawalls.

Artificial structures have become widespread features of coastal marine environments, and will likely proliferate further over the coming decades. These constitute new hard substrata in the marine environment which provide a fundamentally different habitat than natural shores. Eco-engineering solutions aim to ameliorate these differences by combining ecological knowledge and engineering criteria in the construction and modification of artificial substrata. Vertipools™ are artificial bolt-on rockpools intended for deployment on seawalls, where they have been shown to provide biodiversity benefits. In this study, a total of 32 Vertipools were retrofitted on eight seawalls in different environmental contexts (estuarine vs marine and urban vs rural) along the Irish Sea coastline, and were exposed to the environment for a period of two years. After two years, there were no differences in species richness, species-abundance distributions, diversity, or community composition between the specific environmental contexts examined here. Site-level variation was significant, and communities on Vertipools deployed in marine contexts were more variable in general than those in estuarine contexts. Community composition differed significantly between structural sections of the Vertipools, indicating that different sections provide specific microhabitats for colonisation. This study indicates that Vertipools provide biodiversity benefits in a variety of environmental contexts, and therefore are broadly viable as an eco-engineering solution.

Whole-brain annotation and multi-connectome cell typing quantifies circuit stereotypy in Drosophila.

The fruit fly Drosophila melanogaster combines surprisingly sophisticated behaviour with a highly tractable nervous system. A large part of the fly's success as a model organism in modern neuroscience stems from the concentration of collaboratively generated molecular genetic and digital resources. As presented in our FlyWire companion paper 1 , this now includes the first full brain connectome of an adult animal. Here we report the systematic and hierarchical annotation of this ~130,000-neuron connectome including neuronal classes, cell types and developmental units (hemilineages). This enables any researcher to navigate this huge dataset and find systems and neurons of interest, linked to the literature through the Virtual Fly Brain database 2 . Crucially, this resource includes 4,552 cell types. 3,094 are rigorous consensus validations of cell types previously proposed in the hemibrain connectome 3 . In addition, we propose 1,458 new cell types, arising mostly from the fact that the FlyWire connectome spans the whole brain, whereas the hemibrain derives from a subvolume. Comparison of FlyWire and the hemibrain showed that cell type counts and strong connections were largely stable, but connection weights were surprisingly variable within and across animals. Further analysis defined simple heuristics for connectome interpretation: connections stronger than 10 unitary synapses or providing >1% of the input to a target cell are highly conserved. Some cell types showed increased variability across connectomes: the most common cell type in the mushroom body, required for learning and memory, is almost twice as numerous in FlyWire as the hemibrain. We find evidence for functional homeostasis through adjustments of the absolute amount of excitatory input while maintaining the excitation-inhibition ratio. Finally, and surprisingly, about one third of the cell types proposed in the hemibrain connectome could not yet be reliably identified in the FlyWire connectome. We therefore suggest that cell types should be defined to be robust to inter-individual variation, namely as groups of cells that are quantitatively more similar to cells in a different brain than to any other cell in the same brain. Joint analysis of the FlyWire and hemibrain connectomes demonstrates the viability and utility of this new definition. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open source toolchain for brain-scale comparative connectomics.

Using valve gape analysis to compare sensitivity of native Mytilus edulis to invasive Magallana gigas when exposed to heavy metal contamination.

Coastal ecosystems are ecologically and economically important but are under increasing pressure from numerous anthropogenic sources of stress. Both heavy metal pollution and invasive species pose major environmental concerns that can have significant impacts on marine organisms. It is likely that many stresses will occur simultaneously, resulting in potential cumulative ecological effects. The aim of this study was to compare the relative resilience of an invasive oyster Magallana gigas and a native mussel Mytilus edulis to heavy metal pollution, utilising their valve gape response as an indicator. The gape activity of bivalves has been utilised to monitor a range of potential impacts, including for example oil spills, increased turbidity, eutrophication, heavy metal contamination etc. In this study, Hall effect sensors were used on both the native blue mussel (M. edulis) and the pacific oyster (M. gigas), invasive to Ireland. Mussels were shown to be more responsive to pollution events than oysters, where all heavy metals tested (copper, cadmium, zinc, lead) had an effect on transition frequency though significant differences were only observed for lead and cadmium (Control; > Copper, p = 0.0003; >lead, p = 0.0002; >Cadmium, p = 0.0001). Cadmium had an apparent effect on mussels with specimens from this treatment remaining closed for an average of 45.3% of the time. Similarly, significant effects on the duration of time mussels spent fully open was observed when treated with lead and cadmium (Control; > lead, p = 0.03, > cadmium, p = 0.02). In contrast, oysters displayed no significant difference for any treatment for number of gapes, or duration spent open or closed. Though there was an effect of both zinc and copper on the amount of time spent closed, with averages of 63.2 and 68.7% respectively. This indicates oysters may be potentially more resilient to such pollution events; further boosting their competitive advantage. Future mesocosm or field studies are required to quantify this relative resilience.

Population structure and reproductive states of the dogwhelk Nucella lapillus differ between artificial structures and natural rocky shores.

Artificial structures are an increasingly common feature of coastal marine environments. These structures are poor surrogates of natural rocky shores, and generally support less diverse communities and reduced population sizes. Little is known about sub-lethal effects of such structures in terms of demographic properties and reproductive potential, both of which may influence the dynamics and long-term viability of populations. This study examines the population structure, reproductive states and embryo production of Nucella lapillus populations on artificial structures and natural shores in Ireland and Wales. Population density was measured twice at six natural shores and six artificial structures: once in winter and once in spring. At each sampling, the shell height of 100 individuals from each site was measured. Monthly collections of adult specimens and egg capsules were made at each site from November-January and from March-May, in order to determine sex ratios, reproductive states, and embryo abundances. Artificial structures supported larger individuals and very few juveniles compared to natural shores. Between December and January, natural shores experienced a distinctive pulse in spawning activity followed by a decline in the proportion of females in a reproductive state, whereas on artificial structures the proportion of reproductive females remained relatively stable. Differences observed may be due to a lack of microhabitats on artificial structures, along with subtle variations in structure slope. Eco-engineering interventions, including the addition of refugia such as cracks and crevices, may allow N. lapillus populations on artificial structures to approximate those on natural shores.

Artificial rockpools: Seaweed colonisation and productivity vary between sites but are consistent across environmental contexts.

Artificial structures are widespread features of coastal environments, but are poor surrogates of natural rocky shores because they generally support depauperate assemblages with reduced population sizes. This has generated significant interest in eco-engineering solutions, including retrofitting seawalls with artificial rockpools to increase water retention and provide microhabitats. Although these have proven effective at individual sites, widespread uptake is contingent on evidence of consistent benefits across a range of contexts. In this study, Vertipools™ were retrofitted on eight seawalls in different environmental contexts (urban v rural and estuarine v marine) along the Irish Sea coastline and were monitored regularly for two years. Seaweed colonisation proceeded in a manner similar to patterns described for natural and artificial intertidal systems in general, consisting of early dominance by ephemeral species followed by the appearance and eventual establishment of perennial habitat-formers. After 24 months, species richness did not differ between contexts, but differed between sites. The units supported populations of large habitat-forming seaweeds at all sites. Productivity and community respiration of the colonising communities differed between sites by up to 0.5 mg O2 L-1 min-1, but not across environmental contexts. This study demonstrates that bolt-on rockpools attract similar levels of biotic colonisation and functioning in a variety of temperate environmental contexts, and could be considered for widespread implementation as an eco-engineering solution.

Colonisation after disturbance on artificial structures: The influence of timing and grazing.

Artificial structures are poor surrogates of natural rocky shores, meaning they generally support depauperate assemblages. These differences may result from a combination of recruitment processes, biotic interactions, and structuring by environmental factors. In this study, plots were cleared on two seawalls and two natural shores at two separate timepoints - in August 2020 (summer) and February 2021 (winter) - and monitored over one year to determine the influence of timing of disturbance on recruitment and succession. Additional plots were cleared at one of the seawalls at a single timepoint in August 2020, and exclusion cages were installed to determine the influence of grazing pressure on colonisation; these were monitored for 18 months. Disturbance during winter resulted in higher concentrations of all biofilm components up to 3 months, but did not impact benthic community composition beyond this point. Grazer exclusion on artificial structures increased biofilm concentrations and influenced community composition in comparison to plots on artificial structures without exclusion, while communities on natural surfaces differed in terms of species composition to those on artificial plots at 12 months. We conclude that the timing of routine maintenance works on artificial structures may impact initial biofilm abundances. Furthermore, while grazing pressure does influence community structure on artificial structures, this alone is not sufficient to explain biological differences between artificial structures and natural shores.

The population structure, sex ratio and reproductive potential of limpets (Patella spp.) on natural shores and artificial structures in the Irish Sea.

Artificial structures often support depauperate communities compared to natural rocky shores. Understanding variation in ecological success across shore types, particularly regarding habitat-forming species or those with structuring roles, is important to determine how artificial structure proliferation may influence ecosystem functioning and services. We investigated the population structure, sex ratio and reproductive potential of limpets on natural shores and artificial structures on Irish Sea coasts. Limpets were generally less abundant and Patella vulgata populations were often male dominated on artificial structures compared to natural shores, suggesting that shore type may influence these factors. P. vulgata length varied across sites within the Irish Sea (nested in coast and shore type) in autumn/winter, as well as temporally across sites along the Welsh coast. There was no difference in the proportion of P. vulgata in advanced stages of gonad development across shore types. The results suggest that rip-rap artificial structures may provide a habitat comparable to natural shores, however, the addition of ecological engineering interventions on artificial structures may allow limpet populations to better approximate those on natural shores.

Material type influences the abundance but not richness of colonising organisms on marine structures.

Urbanisation of coastal areas and growth in the blue economy drive the proliferation of artificial structures in marine environments. These structures support distinct ecological communities compared to natural hard substrates, potentially reflecting differences in the materials from which they are constructed. We undertook a meta-analysis of 46 studies to compare the effects of different material types (natural or eco-friendly vs. artificial) on the colonising biota on built structures. Neither the abundance nor richness of colonists displayed consistent patterns of difference between artificial and natural substrates or between eco-friendly and standard concrete. Instead, there were differences in the abundance of organisms (but not richness) between artificial and natural materials, that varied according to material type and by functional group. When compared to biogenic materials and rock, polymer and metal supported significantly lower abundances of total benthic species (in studies assessing sessile and mobile species together), sessile invertebrates and corals (in studies assessing these groups individually). In contrast, non-indigenous species were significantly more abundant on wood than metal. Concrete supported greater abundances of the general community, including habitat-forming species, compared to wood. Our results suggest that the ecological requirements of the biological community, alongside economic, logistic and engineering factors should be considered in material selection for multifunctional marine structures that deliver both engineering and ecological (enhanced abundance and diversity) benefits.

Artificial shorelines lack natural structural complexity across scales.

From microbes to humans, habitat structural complexity plays a direct role in the provision of physical living space, and increased complexity supports higher biodiversity and ecosystem functioning across biomes. Coastal development and the construction of artificial shorelines are altering natural landscapes as humans seek socio-economic benefits and protection from coastal storms, flooding and erosion. In this study, we evaluate how much structural complexity is missing on artificial coastal structures compared to natural rocky shorelines, across a range of spatial scales from 1 mm to 10 s of m, using three remote sensing platforms (handheld camera, terrestrial laser scanner and uncrewed aerial vehicles). Natural shorelines were typically more structurally complex than artificial ones and offered greater variation between locations. However, our results varied depending on the type of artificial structure and the scale at which complexity was measured. Seawalls were deficient at all scales (approx. 20-40% less complex than natural shores), whereas rock armour was deficient at the smallest and largest scales (approx. 20-50%). Our findings reinforce concerns that hardening shorelines with artificial structures simplifies coastlines at organism-relevant scales. Furthermore, we offer much-needed insight into how structures might be modified to more closely capture the complexity of natural rocky shores that support biodiversity.

Fucus vesiculosus populations on artificial structures have potentially reduced fecundity and are dislodged at greater rates than on natural shores.

Artificial structures are widespread features of coastal marine environments. These structures, however, are poor surrogates of natural rocky shores, meaning they generally support depauperate assemblages with reduced population sizes. Little is known about sub-lethal effects of such structures, for example, in terms of demographic properties and reproductive potential that may affect the dynamics and long-term viability of populations. Such understanding is particularly important for ecosystem engineer species, such as the intertidal seaweed Fucus vesiculosus. In this study, F. vesiculosus was sampled on eight artificial structures and eight natural shores along the east coast of Ireland and the west coast of Wales. Algal percentage cover, biomass, density of individuals, and growth rate did not differ between artificial and natural shores. Growth and reproductive cycles were consistent with previous studies for this species. While there was considerable variation from site to site, on average, populations on natural shores produced a higher number of mature receptacles during the peak reproductive period in April, and lower rates of dislodgement than on artificial structures. As F. vesiculosus reach peak reproductive output after 24 months, this suggests that individuals may be removed from populations on artificial structures before reaching their full reproductive potential. In this case, this did not influence density, percentage cover, or biomass, which suggests that F. vesiculosus populations on artificial structures may function similarly to those on natural shores if supported by suitable source populations, but potentially may not persist otherwise.

Microtubules originate asymmetrically at the somatic golgi and are guided via Kinesin2 to maintain polarity within neurons.

Neurons contain polarised microtubule arrays essential for neuronal function. How microtubule nucleation and polarity are regulated within neurons remains unclear. We show that γ-tubulin localises asymmetrically to the somatic Golgi within Drosophila neurons. Microtubules originate from the Golgi with an initial growth preference towards the axon. Their growing plus ends also turn towards and into the axon, adding to the plus-end-out microtubule pool. Any plus ends that reach a dendrite, however, do not readily enter, maintaining minus-end-out polarity. Both turning towards the axon and exclusion from dendrites depend on Kinesin-2, a plus-end-associated motor that guides growing plus ends along adjacent microtubules. We propose that Kinesin-2 engages with a polarised microtubule network within the soma to guide growing microtubules towards the axon; while at dendrite entry sites engagement with microtubules of opposite polarity generates a backward stalling force that prevents entry into dendrites and thus maintains minus-end-out polarity within proximal dendrites.

Quantitative Assessment of Left Ventricular Dysfunction in Fetal Ebstein's Anomaly and Tricuspid Valve Dysplasia.

BACKGROUND: Fetal Ebstein's anomaly and tricuspid valve dysplasia (EA/TVD) are associated with high perinatal mortality relative to pulmonary atresia with intact ventricular septum (PAIVS), despite both requiring redistribution of the cardiac output (CO) to the left ventricle (LV). LV dysfunction is suspected to contribute to adverse outcomes in EA/TVD. OBJECTIVE: We sought to examine global and segmental LV function in fetal EA/TVD with comparison to normal controls and PAIVS. We hypothesized that LV dysfunction in EA/TVD is associated with abnormal LV remodeling and interventricular mechanics. METHODS: We retrospectively identified 63 cases of fetal EA/TVD (40 with retrograde ductal flow) and 22 cases of PAIVS encountered from 2004 to 2015 and compared findings to 77 controls of comparable gestational age. We measured the combined CO and global LV function using two-dimensional, Doppler-derived, deformational (six-segmental vector velocity imaging) and dyssynchrony indices (DIs; SD of time to peak), and a novel global DI. RESULTS: EA/TVD fetuses demonstrated abnormal LV global systolic function with reduced ejection fraction, fractional area change, and CO, while in PAIVS we observed a normal ejection fraction, fractional area change, and CO. PAIVS, but not EA/TVD, demonstrated increased LV sphericity, suggestive of remodeling, and associated enhanced radial function in the third trimester. In contrast, while EA/TVD fetuses had normal LV segmental longitudinal strain, there was abnormal radial segmental deformation and LV dyssynchrony with increased SD of time to peak and DI. CONCLUSIONS: Fetal EA/TVD is associated with a lack of spherical remodeling and presence of mechanical dyssynchrony, which likely contribute to reduced CO and ejection fraction. Clinical monitoring of LV function is warranted in fetal EA/TVD. Further studies incorporating quantification of LV function into prediction models for adverse outcomes are required.

The incremental benefit of color tissue doppler in fetal arrhythmia assessment

BACKGROUND: Accurate fetal arrhythmia (FA) diagnosis is key for effective management. Currently, FA assessment relies on standard echocardiography-based techniques (M mode and spectral Doppler), which require adequate fetal position and cursor alignment to define temporal relationships of mechanical events. Few data exist on the application of color Doppler tissue imaging (c-DTI) in FA assessment. The aim of this study was to examine the feasibility and clinical applicability of c-DTI in FA assessment in comparison with standard techniques. METHODS: Pregnancies with diagnosed FA were prospectively recruited to undergo c-DTI following fetal echocardiography. Multiple-cycle four-chamber clips in any orientation were recorded (mean frame rate, 180 ± 16 frames/sec). With offline analysis, sample volumes were placed on atrial (A) and ventricular (V) free walls for simultaneous recordings. Atrial and ventricular rates, intervals (for atrial-ventricular conduction and tachyarrhythmia mechanism), and relationships were assessed to decipher FA mechanism. FA diagnosis by c-DTI, conventional echocardiographic techniques, and postnatal electrocardiography and/or Holter monitoring were compared. RESULTS: FA was assessed by c-DTI in 45 pregnancies at 15 to 39 weeks, including 16 with atrial and/or ventricular ectopic beats; 18 with supraventricular tachyarrhythmias, including ectopic atrial tachycardia in 11, atrioventricular reentrant tachycardia in four, atrial flutter in two, and intermittent atrial flutter and junctional ectopic rhythm in one; three with ventricular tachycardias; and eight with bradycardias or atrioventricular conduction pathology, including five with complete atrioventricular block (AVB), one with first-degree AVB evolving into complete AVB, one with second-degree AVB, and one with sinus bradycardia. After training, FA diagnosis by c-DTI could be made irrespective of fetal orientation within 10 to 15 min. FA diagnosis by c-DTI concurred with standard techniques in 41 cases (91%), with additional findings identified by c-DTI in 10. c-DTI led to new FA diagnoses in four cases (9%) not definable by standard techniques. FA diagnosis by c-DTI was confirmed in all 20 with persistent arrhythmias after birth, including three with new diagnoses defined by c-DTI. c-DTI was particularly helpful in deciphering SVT mechanism (long vs short ventricular-atrial interval) in all 18 cases, whereas standard techniques permitted definition in only half. CONCLUSIONS: c-DTI with offline analysis permits rapid and accurate definition of FA mechanism, providing new information in nearly one-third of affected pregnancies. AU

The Incremental Benefit of Color Tissue Doppler in Fetal Arrhythmia Assessment.

BACKGROUND: Accurate fetal arrhythmia (FA) diagnosis is key for effective management. Currently, FA assessment relies on standard echocardiography-based techniques (M mode and spectral Doppler), which require adequate fetal position and cursor alignment to define temporal relationships of mechanical events. Few data exist on the application of color Doppler tissue imaging (c-DTI) in FA assessment. The aim of this study was to examine the feasibility and clinical applicability of c-DTI in FA assessment in comparison with standard techniques. METHODS: Pregnancies with diagnosed FA were prospectively recruited to undergo c-DTI following fetal echocardiography. Multiple-cycle four-chamber clips in any orientation were recorded (mean frame rate, 180 ± 16 frames/sec). With offline analysis, sample volumes were placed on atrial (A) and ventricular (V) free walls for simultaneous recordings. Atrial and ventricular rates, intervals (for atrial-ventricular conduction and tachyarrhythmia mechanism), and relationships were assessed to decipher FA mechanism. FA diagnosis by c-DTI, conventional echocardiographic techniques, and postnatal electrocardiography and/or Holter monitoring were compared. RESULTS: FA was assessed by c-DTI in 45 pregnancies at 15 to 39 weeks, including 16 with atrial and/or ventricular ectopic beats; 18 with supraventricular tachyarrhythmias, including ectopic atrial tachycardia in 11, atrioventricular reentrant tachycardia in four, atrial flutter in two, and intermittent atrial flutter and junctional ectopic rhythm in one; three with ventricular tachycardias; and eight with bradycardias or atrioventricular conduction pathology, including five with complete atrioventricular block (AVB), one with first-degree AVB evolving into complete AVB, one with second-degree AVB, and one with sinus bradycardia. After training, FA diagnosis by c-DTI could be made irrespective of fetal orientation within 10 to 15 min. FA diagnosis by c-DTI concurred with standard techniques in 41 cases (91%), with additional findings identified by c-DTI in 10. c-DTI led to new FA diagnoses in four cases (9%) not definable by standard techniques. FA diagnosis by c-DTI was confirmed in all 20 with persistent arrhythmias after birth, including three with new diagnoses defined by c-DTI. c-DTI was particularly helpful in deciphering SVT mechanism (long vs short ventricular-atrial interval) in all 18 cases, whereas standard techniques permitted definition in only half. CONCLUSIONS: c-DTI with offline analysis permits rapid and accurate definition of FA mechanism, providing new information in nearly one-third of affected pregnancies.

Reactive oxygen species regulate activity-dependent neuronal plasticity in Drosophila.

Reactive oxygen species (ROS) have been extensively studied as damaging agents associated with ageing and neurodegenerative conditions. Their role in the nervous system under non-pathological conditions has remained poorly understood. Working with the Drosophila larval locomotor network, we show that in neurons ROS act as obligate signals required for neuronal activity-dependent structural plasticity, of both pre- and postsynaptic terminals. ROS signaling is also necessary for maintaining evoked synaptic transmission at the neuromuscular junction, and for activity-regulated homeostatic adjustment of motor network output, as measured by larval crawling behavior. We identified the highly conserved Parkinson's disease-linked protein DJ-1ß as a redox sensor in neurons where it regulates structural plasticity, in part via modulation of the PTEN-PI3Kinase pathway. This study provides a new conceptual framework of neuronal ROS as second messengers required for neuronal plasticity and for network tuning, whose dysregulation in the ageing brain and under neurodegenerative conditions may contribute to synaptic dysfunction.