Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force.

OBJECTIVE: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. METHODS: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. RESULTS: The Task Force proposed two definitions of remission: 'cSLE clinical remission on steroids (cCR)' and 'cSLE clinical remission off steroids (cCR-0)'. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0-3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. CONCLUSIONS: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.

HPV DNA Testing and Mobile Colposcopy for Cervical Precancer Screening in HIV Positive Women: A Comparison Between Two Settings in Ghana and Recommendation for Screening.

INTRODUCTION: Women living with HIV (WLHIV) have higher prevalence and persistence rates of high-risk human papillomavirus (hr-HPV) infection with a six-fold increased risk of cervical cancer. Thus, more frequent screening is recommended for WLHIV. OBJECTIVES: This retrospective descriptive cross-sectional study was conducted to investigate and compare the prevalence of hr-HPV infection and abnormal findings on mobile colposcopy in two cohorts of WLHIV following cervical screening in rural and urban settings in Ghana. METHODS: Through the mPharma 10 000 Women Initiative, WLHIV were screened via concurrent hr-HPV DNA testing (MA-6000; Sansure Biotech Inc., Hunan, China) and visual inspection (Enhanced Visual Assessment [EVA] mobile colposcope; MobileODT, Tel Aviv, Israel) by trained nurses. The women were screened while undergoing routine outpatient reviews at HIV clinics held at the Catholic Hospital, Battor (rural setting) and Tema General Hospital (urban setting), both in Ghana. RESULTS: Two-hundred and fifty-eight WLHIV were included in the analysis (rural, n = 132; urban, n = 126). The two groups were comparable in terms of age, time since HIV diagnosis, and duration of treatment for HIV. The hr-HPV prevalence rates were 53.7% (95% CI, 45.3-62.3) and 48.4% (95% CI, 39.7-57.1) among WLHIV screened in the rural vs urban settings (p-value = .388). Abnormal colposcopy findings were found in 8.5% (95% CI, 5.1-11.9) of the WLHIV, with no significant difference in detection rates between the two settings (p-value = .221). Three (13.6%) of 22 women who showed abnormal colposcopic findings underwent loop electrosurgical excision procedure (LEEP), leaving 19/22 women from both rural and urban areas with pending treatment/follow-up results, which demonstrates the difficulty faced in reaching early diagnosis and treatment, regardless of their area of residence. Histopathology following LEEP revealed CIN III in 2 WLHIV (urban setting, both hr-HPV negative) and CIN I in 1 woman in the rural setting (hr-HPV positive). CONCLUSIONS: There is a high prevalence of hr-HPV among WLHIV in both rural and urban settings in this study in Ghana. Concurrent HPV DNA testing with a visual inspection method (colposcopy/VIA) reduces loss to follow-up compared to performing HPV DNA testing as a standalone test and recalling hr-HPV positive women for follow up with a visual inspection method. Concurrent HPV DNA testing and a visual inspection method may also pick up precancerous cervical lesions that are hr-HPV negative and may be missed if HPV DNA testing is performed alone.

First-trimester cavum veli interpositi: prevalence and natural history.

OBJECTIVE: To confirm the identity and assess the prevalence and evolution of the fluid-filled interhemispheric midline structure, thought to be the cavum veli interpositi (CVI), in fetuses at 11-14 weeks' gestation. METHODS: This was a retrospective study of first-trimester ultrasound scans performed at a single center over 3 months. Inclusion criteria were singleton pregnancies at 11-14 weeks' gestation with known neonatal outcome. Five experts reviewed the images. Mixed-effects logistic regression and generalized estimating equations (GEE) were conducted to analyze the associations between the presence of the structure and variables including ultrasound approach (transabdominal vs transvaginal), maternal body mass index (BMI), gestational age, fetal crown-rump length (CRL) and biparietal diameter (BPD). Second-trimester ultrasound scans of the fetal central nervous system at 18-24 weeks' gestation were evaluated for the persistence of the CVI in fetuses in which the structure was observed in the first trimester. RESULTS: Of the 223 cases reviewed, 104 were included, among which the CVI was observed in 25 (24%) cases. There was no statistically significant difference in CVI visualization between transabdominal and transvaginal ultrasound examinations. GEE showed significant associations between the presence of the fetal structure and CRL (odds ratio (OR) per 10-unit increase, 1.32; P < 0.0001) and BPD (OR per 10-unit increase, 1.88; P = 0.0011). Maternal BMI and gestational age showed no significant effect on the presence of the CVI. At second-trimester follow-up of the 25 fetuses in which the CVI was observed initially, 44% still showed a CVI, 32% exhibited a cavum vergae, 4% had both structures and 20% had neither. CONCLUSIONS: Based on its anatomical location and, in some fetuses, its visualization as a distinct entity from the third ventricle, the identity of the interhemispheric midline structure in the suprathalamic region of the fetal brain between 11-14 weeks' gestation was confirmed as the CVI. The CVI and/or cavum vergae persisted into the second trimester in 80% of fetuses identified initially as having a CVI. Its presence is not linked to pathology, offering reassurance to practitioners and parents. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Differential Neuroanatomical, Neurochemical, and Behavioral Impacts of Early-Age Isolation in a Eusocial Insect.

INTRODUCTION: Social experience early in life appears to be necessary for the development of species-typical behavior. Although isolation during critical periods of maturation has been shown to impact behavior by altering gene expression and brain development in invertebrates and vertebrates, workers of some ant species appear resilient to social deprivation and other neurobiological challenges that occur during senescence or due to loss of sensory input. It is unclear if and to what degree neuroanatomy, neurochemistry, and behavior will show deficiencies if social experience in the early adult life of worker ants is compromised. METHODS: We reared newly-eclosed adult workers of Camponotus floridanus under conditions of social isolation for 2 to 53 days, quantified brain compartment volumes, recorded biogenic amine levels in individual brains, and evaluated movement and behavioral performance to compare the neuroanatomy, neurochemistry, brood-care behavior, and foraging (predatory behavior) of isolated workers with that of workers experiencing natural social contact after adult eclosion. RESULTS: We found that the volume of the antennal lobe, which processes olfactory inputs, was significantly reduced in workers isolated for an average of 40 days, whereas the size of the mushroom bodies, centers of higher-order sensory processing, increased after eclosion and was not significantly different from controls. Titers of the neuromodulators serotonin, dopamine, and octopamine remained stable and were not significantly different in isolation treatments and controls. Brood care, predation, and overall movement were reduced in workers lacking social contact early in life. CONCLUSION: These results suggest that the behavioral development of isolated workers of C. floridanus is specifically impacted by a reduction in the size of the antennal lobe. Task performance and locomotor ability therefore appear to be sensitive to a loss of social contact through a reduction of olfactory processing ability rather than change in the size of the mushroom bodies, which serve important functions in learning and memory, or the central complex, which controls movement.

The acceptability, practicality, implementation and efficacy of a physical and social activity intervention 'BreatheHappy' for people with long-term respiratory conditions: A feasibility study.

OBJECTIVES: This study aimed to determine the feasibility of a group-based pilot programme of low-to-moderate physical activity training, education and social activities, by investigating acceptability, practicality, implementation and efficacy testing. We offer suggestions on programme adaptions for future study. METHODS: People with a range of chronic respiratory diseases were invited to participate in a pilot 12 week group activity programme. Activities included outdoor walking, tai-chi, education and a range of social activities. Acceptability was determined by participant experiences determined during interviews. Practicality was determined by programme and outcome measure completion, cost and adverse events. Implementation was determined according to whether the programme ran as planned. Efficacy was determined by statistical analyses of outcomes including hand grip strength, timed up and go test, COPD Helplessness Index, COPD Assessment Test, and measures of physical activity via accelerometry. RESULTS: Thematic analysis indicated that the "BreatheHappy" programme was acceptable. Seven of nine participants completed eight out of 10 sessions and the majority completed all outcome measures. "BreatheHappy" was therefore considered practical. The programme was not implemented as planned, with only 10 sessions running rather than the 12 intended. There was a significant increase in daily step counts (MD: 1284 95% CI: 240-2329 p: 0.024 effect size: 0.988), stepping time (MD: 16 min 95% CI: 5-27 min p: 0.011 effect size: 1.36) and daily minutes completing light physical activity (MD: 23 95% CI: 6-38 p: 0.006 effect size: 1.6). However, time spent sitting for ≥30 min but ≤60 min significantly increased (MD: 26 95% CI: 0.2-52 min p: 0.049 effect size: 0.931), showing signs of efficacy and changing physical activity behaviour patterns. DISCUSSION: A 10-week programme of low-moderate physical activity training, education and social activities shows signs of feasibility for future research. Suggested adaptions for future study include using physical activity measures such as daily step count or light physical activity for a primary outcome, and mental health and social health related outcome measures relatable to participant's beneficial experiences of the programme. Recruitment in future studies will try and reach both those less socially active and possibly those who have completed pulmonary rehabilitation (PR). Venues should be close to efficient transport links whilst different frequencies and durations of programme delivery should be trialled. Adequate funding should be provided for both staff running the programme and blinded research staff for outcome measurement.

PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS).

OBJECTIVE: To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials. METHODS: The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria. RESULTS: The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0-3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics. CONCLUSIONS: A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.

Proof-of-Principle Experiment on the Dynamic Shell Formation for Inertial Confinement Fusion.

In the dynamic-shell (DS) concept [V. N. Goncharov et al., Novel Hot-Spot Ignition Designs for Inertial Confinement Fusion with Liquid-Deuterium-Tritium Spheres, Phys. Rev. Lett. 125, 065001 (2020).PRLTAO0031-900710.1103/PhysRevLett.125.065001] for laser-driven inertial confinement fusion the deuterium-tritium fuel is initially in the form of a homogeneous liquid inside a wetted-foam spherical shell. This fuel is ignited using a conventional implosion, which is preceded by a initial compression of the fuel followed by its expansion and dynamic formation of a high-density fuel shell with a low-density interior. This Letter reports on a scaled-down, proof-of-principle experiment on the OMEGA laser demonstrating, for the first time, the feasibility of DS formation. A shell is formed by convergent shocks launched by laser pulses at the edge of a plasma sphere, with the plasma itself formed as a result of laser-driven compression and relaxation of a surrogate plastic-foam ball target. Three x-ray diagnostics, namely, 1D spatially resolved self-emission streaked imaging, 2D self-emission framed imaging, and backlighting radiography, have shown good agreement with the predicted evolution of the DS and its stability to low Legendre mode perturbations introduced by laser irradiation and target asymmetries.

First Observation of Cyclotron Radiation from MeV-Scale e

We present an apparatus for detection of cyclotron radiation yielding a frequency-based ß^{±} kinetic energy determination in the 5 keV to 2.1 MeV range, characteristic of nuclear ß decays. The cyclotron frequency of the radiating ß particles in a magnetic field is used to determine the ß energy precisely. Our work establishes the foundation to apply the cyclotron radiation emission spectroscopy (CRES) technique, developed by the Project 8 Collaboration, far beyond the 18-keV tritium endpoint region. We report initial measurements of ß^{-}'s from ^{6}He and ß^{+}'s from ^{19}Ne decays to demonstrate the broadband response of our detection system and assess potential systematic uncertainties for ß spectroscopy over the full (MeV) energy range. To our knowledge, this is the first direct observation of cyclotron radiation from individual highly relativistic ß's in a waveguide. This work establishes the application of CRES to a variety of nuclei, opening its reach to searches for new physics beyond the TeV scale via precision ß-decay measurements.

Cellular microarrays for assessing single-cell phenotypic changes in vascular cell populations.

Microengineering technologies provide bespoke tools for single-cell studies, including microarray approaches. There are many challenges when culturing adherent single cells in confined geometries for extended periods, including the ability of migratory cells to overcome confining cell-repellent surfaces with time. Following studies suggesting clonal expansion of only a few vascular smooth muscle cells (vSMCs) contributes to plaque formation, the investigation of vSMCs at the single-cell level is central to furthering our understanding of atherosclerosis. Herein, we present a medium throughput cellular microarray, for the tracking of single, freshly-isolated vSMCs as they undergo phenotypic modulation in vitro. Our solution facilitates long-term cell confinement (> 3 weeks) utilising novel application of surface functionalisation methods to define individual culture microwells. We demonstrate successful tracking of hundreds of native vSMCs isolated from rat aortic and carotid artery tissue, monitoring their proliferative capacity and uptake of oxidised low-density lipoprotein (oxLDL) by live-cell microscopy. After 7 days in vitro, the majority of viable SMCs remained as single non-proliferating cells (51% aorta, 78% carotid). However, a sub-population of vSMCs demonstrated high proliferative capacity (≥ 10 progeny; 18% aorta, 5% carotid), in line with reports that a limited number of medial SMCs selectively expand to populate atherosclerotic lesions. Furthermore, we show that, when exposed to oxLDL, proliferative cells uptake higher levels of lipoproteins, whilst also expressing greater levels of galectin-3. Our microwell array approach enables long-term characterisation of multiple phenotypic characteristics and the identification of new cellular sub-populations in migratory, proliferative adherent cell types.

Non-equilibrium molecular simulations of thin film rupture.

The retraction of thin films, as described by the Taylor-Culick (TC) theory, is subject to widespread debate, particularly for films at the nanoscale. We use non-equilibrium molecular dynamics simulations to explore the validity of the assumptions used in continuum models by tracking the evolution of holes in a film. By deriving a new mathematical form for the surface shape and considering a locally varying surface tension at the front of the retracting film, we reconcile the original theory with our simulation to recover a corrected TC speed valid at the nanoscale.

Impacts of colonization on Indigenous food systems in Canada and the United States: a scoping review.

BACKGROUND: Indigenous populations in Canada and the United States (US) have maintained reciprocal relationships with nature, grounded in respect for and stewardship of the environment; however, disconnection from traditional food systems has generated a plethora of physical and mental health challenges for communities. Indigenous food sovereignty including control of lands were found to be factors contributing to these concerns. Therefore, our aim was to conduct a scoping review of the peer-reviewed literature to describe Indigenous disconnection from Indigenous food systems (IFS) in Canada and the US. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-SR) and Joanna Briggs Institute guidelines, we searched MEDLINE, SCOPUS, International Bibliography of the Social Sciences, Sociological Abstracts, and Bibliography of Native North Americans. Data was extracted from 41 studies and a narrative review completed based on study themes. RESULTS: The overarching theme identified in the included studies was the impact of colonization on IFS. Four sub-themes emerged as causes for Indigenous disconnection from traditional food systems, including: climate change; capitalism; legal change; and socio-cultural change. These sub-themes highlight the multiple ways in which colonization has impacted Indigenous food systems in Canada and the US and important areas for transformation. CONCLUSIONS: Efforts to reconnect Indigenous knowledge and values systems with future food systems are essential for planetary health and sustainable development. Traditional knowledge sharing must foreground authentic Indigenous inclusion within policymaking.

Exploring the Use of the Behavior Change Technique Taxonomy and the Persuasive System Design Model in Defining Parent-Focused eHealth Interventions: Scoping Review.

BACKGROUND: Taxonomies and models are useful tools for defining eHealth content and intervention features, enabling comparison and analysis of research across studies and disciplines. The Behavior Change Technique Taxonomy version 1 (BCTTv1) was developed to decrease ambiguity in defining specific characteristics inherent in health interventions, but it was developed outside the context of digital technology. In contrast, the Persuasive System Design Model (PSDM) was developed to define and evaluate the persuasive content in software solutions but did not have a specific focus on health. Both the BCTTv1 and PSDM have been used to define eHealth interventions in the literature, with some researchers combining or reducing the taxonomies to simplify their application. It is unclear how well the taxonomies accurately define eHealth and whether they should be used alone or in combination. OBJECTIVE: This scoping review explored how the BCTTv1 and PSDM capture the content and intervention features of parent-focused eHealth as part of a program of studies investigating the use of technology to support parents with therapy home programs for children with special health care needs. It explored the active ingredients and persuasive technology features commonly found in parent-focused eHealth interventions for children with special health care needs and how the descriptions overlap and interact with respect to the BCTTv1 and PSDM taxonomies. METHODS: A scoping review was used to clarify concepts in the literature related to these taxonomies. Keywords related to parent-focused eHealth were defined and used to systematically search several electronic databases for parent-focused eHealth publications. Publications referencing the same intervention were combined to provide comprehensive intervention details. The data set was coded using codebooks developed from the taxonomies in NVivo (version 12; QSR International) and qualitatively analyzed using matrix queries. RESULTS: The systematic search found 23 parent-focused eHealth interventions described in 42 articles from various countries; delivered to parents with children aged 1 to 18 years; and covering medical, behavioral, and developmental issues. The predominant active ingredients and intervention features in parent-focused eHealth were concerned with teaching parents behavioral skills, encouraging them to practice and monitor the new skills, and tracking the outcomes of performing the new skills. No category had a complete set of active ingredients or intervention features coded. The two taxonomies conceptually captured different constructs even when their labels appeared to overlap in meaning. In addition, coding by category missed important active ingredients and intervention features. CONCLUSIONS: The taxonomies were found to code different constructs related to behavior change and persuasive technology, discouraging the merging or reduction of the taxonomies. This scoping review highlighted the benefit of using both taxonomies in their entirety to capture active ingredients and intervention features important for comparing and analyzing eHealth across different studies and disciplines. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-doi.org/10.15619/nzjp/47.1.05.

Women's preferences for pelvic floor screening in sport and exercise: a mixed-methods study integrating survey and interview data in Australian women.

OBJECTIVES: One in two women experiencing pelvic floor (PF) symptoms stop playing sport or exercising. The study examines the perspective of women with PF symptoms to inform acceptable screening practices within sport and exercise settings. METHODS: Explanatory, sequential, mixed-methods design. Phase 1: survey of 18-65 years, symptomatic, Australian women (n=4556). Phase 2: semistructured interviews with a subset of survey participants (n=23). Integration occurred through connection of phases (study design, sampling) and joint display of data. RESULTS: Findings are represented in three threads: (1) 'women (not) telling'; a majority of women had told no-one within a sport or exercise setting about their PF symptoms due to shame/embarrassment, lack of pelvic health knowledge and not wanting to initiate the conversation, (2) 'asking women (screening for PF symptoms)'; women endorsed including PF symptom questions within existing sport and exercise screening practices but only when conducted in a respectful and considered manner and (3) 'creating safety'; professionals can assist women to disclose by demonstrating expertise, trustworthiness and competency. If health and exercise professionals are provided with appropriate training, they could raise pelvic health awareness and promote a supportive and safe sport and exercise culture. CONCLUSION: Women with PF symptoms support health and exercise professionals initiating conversations about PF health to normalise the topic, and include PF symptoms among other pre-exercise screening questions. However, women should be informed on the relevance and potential benefits of PF screening prior to commencing. Safe screening practices require building trust by providing information, gaining consent, displaying comfort and genuine interest, and being knowledgeable within one's scope of practice to the provision of advice, exercise modifications and referral as appropriate.

Altered sacral neural crest development in Pax3 spina bifida mutants underlies deficits of bladder innervation and function.

Mouse models of Spina bifida (SB) have been instrumental for identifying genes, developmental processes, and environmental factors that influence neurulation and neural tube closure. Beyond the prominent neural tube defects, other aspects of the nervous system can be affected in SB with significant changes in essential bodily functions such as urination. SB patients frequently experience bladder dysfunction and SB fetuses exhibit reduced density of bladder nerves and smooth muscle although the developmental origins of these deficits have not been determined. The Pax3 Splotch-delayed (Pax3Sp-d) mouse model of SB is one of a very few mouse SB models that survives to late stages of gestation. Through analysis of Pax3Sp-d mutants we sought to define how altered bladder innervation in SB might arise by tracing sacral neural crest (NC) development, pelvic ganglia neuronal differentiation, and assessing bladder nerve fiber density. In Pax3Sp-d/Sp-d fetal mice we observed delayed migration of Sox10+ NC-derived progenitors (NCPs), deficient pelvic ganglia neurogenesis, and reduced density of bladder wall innervation. We further combined NC-specific deletion of Pax3 with the constitutive Pax3Sp-d allele in an effort to generate viable Pax3 mutants to examine later stages of bladder innervation and postnatal bladder function. Neural crest specific deletion of a Pax3 flox allele, using a Sox10-cre driver, in combination with a constitutive Pax3Sp-d mutation produced postnatal viable offspring that exhibited altered bladder function as well as reduced bladder wall innervation and altered connectivity between accessory ganglia at the bladder neck. Combined, the results show that Pax3 plays critical roles within sacral NC that are essential for initiation of neurogenesis and differentiation of autonomic neurons within pelvic ganglia.

Sox10-cre BAC transgenes reveal temporal restriction of mesenchymal cranial neural crest and identify glandular Sox10 expression.

Diversity of neural crest derivatives has been studied with a variety of approaches during embryonic development. In mammals Cre-LoxP lineage tracing is a robust means to fate map neural crest relying on cre driven from regulatory elements of early neural crest genes. Sox10 is an essential transcription factor for normal neural crest development. A variety of efforts have been made to label neural crest derivatives using partial Sox10 regulatory elements to drive cre expression. To date published Sox10-cre lines have focused primarily on lineage tracing in specific tissues or during early fetal development. We describe two new Sox10-cre BAC transgenes, constitutive (cre) and inducible (cre/ERT2), that contain the complete repertoire of Sox10 regulatory elements. We present a thorough expression profile of each, identifying a few novel sites of Sox10 expression not captured by other neural crest cre drivers. Comparative mapping of expression patterns between the Sox10-cre and Sox10-cre/ERT2 transgenes identified a narrow temporal window in which Sox10 expression is present in mesenchymal derivatives prior to becoming restricted to neural elements during embryogenesis. In more caudal structures, such as the intestine and lower urinary tract, our Sox10-cre BAC transgene appears to be more efficient in labeling neural crest-derived cell types than Wnt1-cre. The analysis reveals consistent expression of Sox10 in non-neural crest derived glandular epithelium, including salivary, mammary, and urethral glands of adult mice. These Sox10-cre and Sox10-cre/ERT2 transgenic lines are verified tools that will enable refined temporal and cell-type specific lineage analysis of neural crest derivatives as well as glandular tissues that rely on Sox10 for proper development and function.

Combinatorial Transcriptional Profiling of Mouse and Human Enteric Neurons Identifies Shared and Disparate Subtypes In Situ.

BACKGROUND & AIMS: The enteric nervous system (ENS) coordinates essential intestinal functions through the concerted action of diverse enteric neurons (ENs). However, integrated molecular knowledge of EN subtypes is lacking. To compare human and mouse ENs, we transcriptionally profiled healthy ENS from adult humans and mice. We aimed to identify transcripts marking discrete neuron subtypes and visualize conserved EN subtypes for humans and mice in multiple bowel regions. METHODS: Human myenteric ganglia and adjacent smooth muscle were isolated by laser-capture microdissection for RNA sequencing. Ganglia-specific transcriptional profiles were identified by computationally subtracting muscle gene signatures. Nuclei from mouse myenteric neurons were isolated and subjected to single-nucleus RNA sequencing, totaling more than 4 billion reads and 25,208 neurons. Neuronal subtypes were defined using mouse single-nucleus RNA sequencing data. Comparative informatics between human and mouse data sets identified shared EN subtype markers, which were visualized in situ using hybridization chain reaction. RESULTS: Several EN subtypes in the duodenum, ileum, and colon are conserved between humans and mice based on orthologous gene expression. However, some EN subtype-specific genes from mice are expressed in completely distinct morphologically defined subtypes in humans. In mice, we identified several neuronal subtypes that stably express gene modules across all intestinal segments, with graded, regional expression of 1 or more marker genes. CONCLUSIONS: Our combined transcriptional profiling of human myenteric ganglia and mouse EN provides a rich foundation for developing novel intestinal therapeutics. There is congruency among some EN subtypes, but we note multiple species differences that should be carefully considered when relating findings from mouse ENS research to human gastrointestinal studies.

Reduced hip bone mineral density is associated with high levels of calciprotein particles in patients with Fabry disease.

Calciprotein particles (CPP) are nanoscale mineralo-protein aggregates that help stabilize excess mineral in the circulation. We examined the relationship between CPP and bone mineral density in Fabry disease patients. We found an inverse correlation with total hip and femoral neck density, but none with lumbar spine. PURPOSE: Calciprotein particles (CPP) are colloidal mineral-protein complexes made up primarily of the circulating glycoprotein fetuin-A, calcium, and phosphate. They form in extracellular fluid and facilitate the stabilization, transport, and clearance of excess minerals from the circulation. While most are monomers, they also exist in larger primary (CPP-I) and secondary (CPP-II) form, both of which are reported to be raised in pathological states. This study sought to investigate CPP levels in the serum of patients with Fabry disease, an X-linked systemic lysosomal storage disorder that is associated with generalized inflammation and low bone mineral density (BMD). METHODS: We compared serum CPP-I and CPP-II levels in 59 patients with Fabry disease (37 female) with levels in an age-matched healthy adult cohort (n=28) and evaluated their association with BMD and biochemical data obtained from routine clinical review. RESULTS: CPP-I and CPP-II levels were higher in male Fabry disease patients than female sufferers as well as their corresponding sex- and age-matched controls. CPP-II levels were inversely correlated with BMD at the total hip and femoral neck, but not the lumbar spine. Regression analyses revealed that these associations were independent of common determinants of BMD, but at the femoral neck, a significant association was only found in female patients. CONCLUSION: Low hip BMD was associated with high CPP-II in patients with Fabry disease, but further work is needed to investigate the relevance of sex-related differences and to establish whether CPP measurement may aid assessment of bone disease in this setting.

The Intrinsic Fragility of the Liquid-Vapor Interface: A Stress Network Perspective.

The evolution of the liquid-vapor interface of a Lennard-Jones fluid is examined with molecular dynamics simulations using the intrinsic sampling method. Results suggest clear damping of the intrinsic profiles with increasing temperature. Investigating the surface stress distribution, we have identified a linear variation of the space-filling nature (fractal dimension) of the stress clusters at the intrinsic surface with increasing surface tension or, equivalently, with decreasing temperature. A percolation analysis of these stress networks indicates that the stress field is more disjointed at higher temperatures. This leads to more fragile (or poorly connected) interfaces which result in a reduction in surface tension.

The effect of continuous venovenous hemodiafiltration on amino acid delivery, clearance, and removal in children.

BACKGROUND: In critically ill children with acute kidney injury (AKI), continuous kidney replacement therapy (CKRT) enables nutrition provision. The magnitude of amino acid loss during continuous venovenous hemodiafiltration (CVVHDF) is unknown and needs accurate quantification. We investigated the mass removal and clearance of amino acids in pediatric CVVHDF. METHODS: This is a prospective observational cohort study of patients receiving CVVHDF from August 2014 to January 2016 in the pediatric intensive care unit (PICU) of a tertiary children's hospital. RESULTS: Fifteen patients (40% male, median age 2.0 (IQR 0.7, 8.0) years) were enrolled. Median PICU and hospital lengths of stay were 20 (9, 59) and 36 (22, 132) days, respectively. Overall survival to discharge was 66.7%. Median daily protein prescription was 2.00 (1.25, 2.80) g/kg/day. Median daily amino acid mass removal was 299.0 (174.9, 452.0) mg/kg body weight, and median daily amino acid mass clearance was 18.2 (13.5, 27.9) ml/min/m2, resulting in a median 14.6 (8.3, 26.7) % protein loss. The rate of amino acid loss increased with increasing dialysis dose and blood flow rate. CONCLUSION: CVVHDF prescription and related amino acid loss impact nutrition provision, with 14.6% of the prescribed protein removed. Current recommendations for protein provision for children requiring CVVHDF should be adjusted to compensate for circuit-related loss. A higher resolution version of the Graphical abstract is available as Supplementary information.

Network analysis of impulse dyscontrol in mild cognitive impairment and subjective cognitive decline.

OBJECTIVES: To investigate conditional dependence relationships of impulse dyscontrol symptoms in mild cognitive impairment (MCI) and subjective cognitive decline (SCD). DESIGN: A prospective, observational study. PARTICIPANTS: Two hundred and thirty-five patients with MCI (n = 159) or SCD (n = 76) from the Prospective Study for Persons with Memory Symptoms dataset. MEASUREMENTS: Items of the Mild Behavioral Impairment Checklist impulse dyscontrol subscale. RESULTS: Stubbornness/rigidity, agitation/aggressiveness, and argumentativeness were frequent and the most central symptoms in the network. Impulsivity, the fourth most central symptom in the network, served as the bridge between these common symptoms and less central and rare symptoms. CONCLUSIONS: Impulse dyscontrol in at-risk states for dementia is characterized by closely connected symptoms of irritability, agitation, and rigidity. Compulsions and difficulties in regulating rewarding behaviors are relatively isolated symptoms.