1H Nuclear Magnetic Resonance Spectroscopy Reveals Changes in Metabolic Phenotype Associated with Disease Stage in Patients with Chronic Venous Disease.

OBJECTIVE: Chronic venous disease (CVD) is a condition presenting a great burden to patients and society, with poorly characterised pathophysiology. Metabolic phenotyping can elucidate mechanisms of disease and identify candidate biomarkers. The aim of this study was to determine differences in the metabolic signature between symptomatic patients with CVD and asymptomatic volunteers using proton nuclear magnetic resonance spectroscopy (1H-NMR). METHODS: This was a prospective case-control study of consecutive patients with symptomatic CVD and asymptomatic volunteers recruited from a single centre. Participants underwent clinical assessment, venous duplex ultrasound, and blood and urine sampling. Disease stage was defined according to the Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification. 1H-NMR experiments were performed, with data analysed via multivariate statistical techniques. RESULTS: A total of 622 participants were recruited, including 517 symptomatic patients with CVD (telangiectasia [C1] 0.6%, varicose veins [C2] 48.5%, swelling [C3] 12.0%, skin changes [C4] 27.7%, healed or active ulceration [C5/6] 11.2%) and 105 asymptomatic participants (no disease [C0] 69.5%, telangiectasia [C1] 29.6%). Multivariate analysis revealed differences between the metabolic profile of the symptomatic CVD and asymptomatic groups, and between CEAP clinical classes in the CVD group. Serum aromatic amino acids positively correlated with increasing CEAP clinical class (p < .001). Urinary formate, creatinine, glycine, citrate, succinate, pyruvate, and 2-hydroxyisobutyrate negatively correlated with increasing CEAP clinical class (p < .001). These metabolites are involved in the tricarboxylic acid cycle, hypoxia inducible factor pathway, and one carbon metabolism. CONCLUSION: Untargeted biofluid analysis via 1H-NMR has detected metabolites associated with the presence and severity of CVD, highlighting biological pathways of relevance and providing candidate biomarkers to explore in future research.

Tracking clonal evolution of drug resistance in ovarian cancer patients by exploiting structural variants in cfDNA.

Drug resistance is the major cause of therapeutic failure in high-grade serous ovarian cancer (HGSOC). Yet, the mechanisms by which tumors evolve to drug resistant states remains largely unknown. To address this, we aimed to exploit clone-specific genomic structural variations by combining scaled single-cell whole genome sequencing with longitudinally collected cell-free DNA (cfDNA), enabling clonal tracking before, during and after treatment. We developed a cfDNA hybrid capture, deep sequencing approach based on leveraging clone-specific structural variants as endogenous barcodes, with orders of magnitude lower error rates than single nucleotide variants in ctDNA (circulating tumor DNA) detection, demonstrated on 19 patients at baseline. We then applied this to monitor and model clonal evolution over several years in ten HGSOC patients treated with systemic therapy from diagnosis through recurrence. We found drug resistance to be polyclonal in most cases, but frequently dominated by a single high-fitness and expanding clone, reducing clonal diversity in the relapsed disease state in most patients. Drug-resistant clones frequently displayed notable genomic features, including high-level amplifications of oncogenes such as CCNE1, RAB25, NOTCH3, and ERBB2. Using a population genetics Wright-Fisher model, we found evolutionary trajectories of these features were consistent with drug-induced positive selection. In select cases, these alterations impacted selection of secondary lines of therapy with positive patient outcomes. For cases with matched single-cell RNA sequencing data, pre-existing and genomically encoded phenotypic states such as upregulation of EMT and VEGF were linked to drug resistance. Together, our findings indicate that drug resistant states in HGSOC pre-exist at diagnosis and lead to dramatic clonal expansions that alter clonal composition at the time of relapse. We suggest that combining tumor single cell sequencing with cfDNA enables clonal tracking in patients and harbors potential for evolution-informed adaptive treatment decisions.

Establishing the Vaccine Safety Health Link: A large, linked data resource for the investigation of vaccine safety concerns.

OBJECTIVE: Post-licensure vaccine safety surveillance of adverse events following immunisation is critical to ensure public safety and confidence in vaccines. This paper aims to describe the governance structure and data linkage methodology behind the establishment of the largest linked vaccine safety surveillance data resource in Australia - The Vaccine Safety Health Link (VSHL). METHODS: The Vaccine Safety Health Link contains linked records from the Australian Immunisation Register with records from hospital, perinatal, mortality, and notifiable disease datasets in near real-time. Linkage is done by the Centre for Victorian Data Linkage who receive the datasets in an identifiable format which then undergo standardisation, enrichment, linkage, quality assurance and de-identification, prior to being supplied for analysis. RESULTS: The VSHL data resource allows sensitive and rapid analysis of a broad spectrum of suspected adverse events to ensure the safety of all vaccines administered. It is also used to refute spurious concerns where no associations are found, upholding trust, and maintaining vaccine confidence. CONCLUSIONS: The Vaccine Safety Health Link's surveillance design complements existing vaccine safety surveillance methods. Challenges encountered and lessons learnt using Vaccine Safety Health Link would benefit linkage projects globally. IMPLICATIONS FOR PUBLIC HEALTH: In its first two years, The Vaccine Safety Health Link has been used for 14 vaccine safety investigations. Studies into these conditions would not have otherwise been possible. The Vaccine Safety Health Link also partners with the Global Vaccine Data Network™ for approved collaborative studies with a combined population of over 300 million people.

Plasma-derived extracellular vesicles (EVs) as biomarkers of sepsis in burn patients via label-free Raman spectroscopy.

Sepsis following burn trauma is a global complication with high mortality, with ∼60% of burn patient deaths resulting from infectious complications. Diagnosing sepsis is complicated by confounding clinical manifestations of the burn injury, and current biomarkers lack the sensitivity and specificity required for prompt treatment. There is a strong rationale to assess circulating extracellular vesicles (EVs) from patient liquid biopsy as sepsis biomarkers due to their release by pathogens from bacterial biofilms and roles in the subsequent immune response. This study applies Raman spectroscopy to patient plasma-derived EVs for rapid, sensitive, and specific detection of sepsis in burn patients, achieving 97.5% sensitivity and 90.0% specificity. Furthermore, spectral differences between septic and non-septic burn patient EVs could be traced to specific glycoconjugates of bacterial strains associated with sepsis morbidity. This work illustrates the potential application of EVs as biomarkers in clinical burn trauma care and establishes Raman analysis as a fast, label-free method to specifically identify features of bacterial EVs relevant to infection amongst the host background.

A Reduced Resistance, Concentric-Gated Artificial Membrane Lung for Pediatric End-Stage Lung Failure.

The goal of the low-resistance pediatric artificial lung (PAL-LR) is to serve as a pumpless bridge-to-transplant device for children with end-stage lung failure. The PAL-LR doubles the exposed fiber length of the previous PAL design. In vitro and in vivo studies tested hemocompatibility, device flow, gas exchange and pressure drop performance. For in vitro tests, average rated blood flow (outlet SO2 of 95%) was 2.56 ± 0.93 L/min with a pressure drop of 25.88 ± 0.90 mm Hg. At the targeted pediatric flow rate of 1 L/min, the pressure drop was 8.6 mm Hg compared with 25 mm Hg of the PAL. At rated flow, the average O2 and CO2 transfer rates were 101.75 ± 10.81 and 77.93 ± 8.40 mL/min, respectively. The average maximum O2 and CO2 exchange efficiencies were 215.75 ± 22.93 and 176.99 ± 8.40 mL/(min m2), respectively. In vivo tests revealed an average outlet SO2 of 100%, and average pressure drop of 2 ± 0 mm Hg for a blood flow of 1.07 ± 0.02 L/min. Having a lower resistance, the PAL-LR is a promising step closer to a pumpless artificial membrane lung that alleviates right ventricular strain associated with idiopathic pulmonary hypertension.

Energy expenditure prediction in preschool children: a machine learning approach using accelerometry and external validation.

Objective.This study aimed to develop convolutional neural networks (CNNs) models to predict the energy expenditure (EE) of children from raw accelerometer data. Additionally, this study sought to external validation of the CNN models in addition to the linear regression (LM), random forest (RF), and full connected neural network (FcNN) models published in Steenbocket al(2019J. Meas. Phys. Behav.294-102).Approach.Included in this study were 41 German children (3.0-6.99 years) for the training and internal validation who were equipped with GENEActiv, GT3X+, and activPAL accelerometers. The external validation dataset consisted of 39 Canadian children (3.0-5.99 years) that were equipped with OPAL, GT9X, GENEActiv, and GT3X+ accelerometers. EE was recorded simultaneously in both datasets using a portable metabolic unit. The protocols consisted of a semi-structured activities ranging from low to high intensities. The root mean square error (RMSE) values were calculated and used to evaluate model performances.Main results.(1) The CNNs outperformed the LM (13.17%-23.81% lower mean RMSE values), FcNN (8.13%-27.27% lower RMSE values) and the RF models (3.59%-18.84% lower RMSE values) in the internal dataset. (2) In contrast, it was found that when applied to the external Canadian dataset, the CNN models had consistently higher RMSE values compared to the LM, FcNN, and RF.Significance.Although CNNs can enhance EE prediction accuracy, their ability to generalize to new datasets and accelerometer brands/models, is more limited compared to LM, RF, and FcNN models.

Maximizing Photon-to-Electron Conversion for Atom Efficient Photoredox Catalysis.

Photoredox catalysis is a powerful tool to access challenging and diverse syntheses. Absorption of visible light forms the excited state catalyst (*PC) but photons may be wasted if one of several unproductive pathways occur. Facile dissociation of the charge-separated encounter complex [PC•-:D•+], also known as (solvent) cage escape, is required for productive chemistry and directly governs availability of the critical PC•- intermediate. Competitive charge recombination, either inside or outside the solvent cage, may limit the overall efficiency of a photochemical reaction or internal quantum yield (defined as the moles of product formed per mole of photons absorbed by PC). Measuring the cage escape efficiency (ϕCE) typically requires time-resolved spectroscopy; however, we demonstrate how to estimate ϕCE using steady-state techniques that measure the efficiency of PC•- formation (ϕPC). Our results show that choice of electron donor critically impacts ϕPC, which directly correlates to improved synthetic and internal quantum yields. Furthermore, we demonstrate how modest structural differences between photocatalysts may afford a sizable effect on reactivity due to changes in ϕPC, and by extension ϕCE. Optimizing experimental conditions for cage escape provides photochemical reactions with improved atom economy and energy input, paving the way for sustainable design of photocatalytic systems.

An Assessment of Adverse Events in Patients with 22q11.2 Deletion Syndrome Undergoing Palatoplasty: An Analysis of the NSQIP Pediatric Database.

BACKGROUND: The National Surgical Quality Improvement Program (NSQIP) Pediatric database has been used to identify factors related to adverse surgical outcomes in pediatric and craniofacial surgical procedures. Focusing on a historically "higher-risk" population, our aim was to assess the impact of demographics, comorbidities, and 22q11.2 deletion syndrome (22QDS) diagnosis on 30-day postoperative complications in patients undergoing primary palatoplasty. METHODS: We used the 2012-2020 NSQIP Pediatric database to identify patients ≤3 years with and without 22q11.2 deletion syndrome who underwent primary palatoplasty. Demographics, comorbidities, and perioperative characteristics were compared between those with and without 22QDS. Logistic regression was used to determine if children with 22QDS were more likely to experience a 30-day postoperative complication or readmission. RESULTS: There were 10,745 patients ≤3 years old who underwent primary palatoplasty; 83 (0.8%) of whom had 22QDS and 10,662 (99.8%) did not. Children with 22QDS were older when they underwent primary palatoplasty and more likely to have comorbidities. A total of 513 patients (4.8%) experienced a postoperative complication within 30 days and 255 were readmitted (2.4%). Of the 513, 8 (9.6%) had a 22QDS diagnosis and 505 (4.7%) did not. A diagnosis of 22QDS was not a significant independent risk factor for a complication (adjusted odds ratio (aOR) = 1.13; 95% confidence interval (CI): 0.50-2.54) or readmission (aOR = 1.74; 95% CI: 0.74-4.13) within 30 days. CONCLUSION: This study found that the diagnosis of 22QDS was not an independent predictor of post-palatoplasty complication risk, and in fact 30-day complications are rare for those patients undergoing cleft palate repair, even among those patients with 22QDS.

Testing maternal effects of vitamin-D and omega-3 levels on offspring neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study.

BACKGROUND: Maternal vitamin-D and omega-3 fatty acid (DHA) deficiencies during pregnancy have previously been associated with offspring neurodevelopmental traits. However, observational study designs cannot distinguish causal effects from confounding. METHODS: First, we conducted Mendelian randomisation (MR) using genetic instruments for vitamin-D and DHA identified in independent genome-wide association studies (GWAS). Outcomes were (1) GWAS for traits related to autism and ADHD, generated in the Norwegian mother, father, and child cohort study (MoBa) from 3 to 8 years, (2) autism and ADHD diagnoses. Second, we used mother-father-child trio-MR in MoBa (1) to test causal effects through maternal nutrient levels, (2) to test effects of child nutrient levels, and (3) as a paternal negative control. RESULTS: Associations between higher maternal vitamin-D levels on lower ADHD related traits at age 5 did not remain after controlling for familial genetic predisposition using trio-MR. Furthermore, we did not find evidence for causal maternal effects of vitamin-D/DHA levels on other offspring traits or diagnoses. In the reverse direction, there was evidence for a causal effect of autism genetic predisposition on lower vitamin-D levels and of ADHD genetic predisposition on lower DHA levels. CONCLUSIONS: Triangulating across study designs, we did not find evidence for maternal effects. We add to a growing body of evidence that suggests that previous observational associations are likely biased by genetic confounding. Consequently, maternal supplementation is unlikely to influence these offspring neurodevelopmental traits. Notably, genetic predisposition to ADHD and autism was associated with lower DHA and vitamin-D levels respectively, suggesting previous associations might have been due to reverse causation.

Decoding the role of tRNA modifications in cancer progression.

Epitranscriptomic modification of tRNA has recently gained traction in the field of cancer biology. The presence of such modifications on tRNA appears to allow for translational control of processes central to progression and malignant transformation. Methyltransferase Like 1 protein (METTL1), along with other epitranscriptomic writers (e.g. NSUN3, NAT10, ELP3, etc.), has recently been investigated in multiple cancer types. Here, we review the impact of such tRNA modifications in tumorigenesis and the progression of cancer toward drug resistance and metastasis. Regulation of central cellular processes relied upon by malignant cancer cells through modulation of the tRNA epitranscriptome represents an area with great potential to bring novel first-in-class therapies to the clinic.

The prevalence of child sexual abuse perpetrated by leaders or other adults in religious organizations in Australia.

BACKGROUND: Numerous national public inquiries have highlighted the problem of child sexual abuse in religious organizations. Despite this, evidence of population-wide prevalence is scarce. OBJECTIVE: To provide the first nationally representative prevalence estimates of child sexual abuse perpetrated by adults in religious organizations in Australia. METHODS: The Australian Child Maltreatment Study (ACMS) surveyed 8503 people aged 16 and over about their experiences of child maltreatment. Weighted prevalence estimates were calculated based on responses to the child sexual abuse questions from the Juvenile Victimization Questionnaire-R2: Adapted Version (ACMS). RESULTS: One in 250 people reported being sexually abused as a child by an adult in a religious organization (0.4 %, 95 % CI, 0.3-0.6 %). Men reported significantly higher rates of child sexual abuse by these perpetrators (0.8 %, 95 % CI, 0.5-1.2 %), compared to women (0.1 %, 95 % CI, 0-0.3 %). This type of sexual abuse was overwhelmingly perpetrated by men (0.4 %, 95 % CI, 0.3-0.6 %), compared to women (0 %, 95 % CI, 0-0.1 %), and was substantially more often experienced in Catholic organizations (71.9 %) than other Christian denominations or other religions. Prevalence of child sexual abuse in religious organizations has declined over time (2.2 % of men 65 years and older, compared with 0.2 % of 16-24-year-old men). CONCLUSIONS: Child sexual abuse has been widespread in religious organizations in Australia. A decline over time indicates progress has been made in preventing sexual abuse of children. Religious organizations must take all reasonable measures to prevent child sexual abuse, with a particular need for interventions targeting male leaders, and organizational cultures.

End-of-life experiences in individuals with dementia with Lewy bodies and their caregivers: A mixed-methods analysis.

BACKGROUND: Dementia with Lewy bodies (DLB) is one of the most common degenerative dementias, but research on end-of-life experiences for people with DLB and their caregivers is limited. METHOD: Dyads of individuals with moderate-advanced DLB and their primary informal caregivers were recruited from specialty clinics, advocacy organizations, and research registries and followed prospectively every 6 months. The current study examines results of caregiver study visits 3 months after the death of the person with DLB. These visits included the Last Month of Life survey, study-specific questions, and a semi-structured interview querying end-of-life experiences. RESULTS: Individuals with DLB (n = 50) died 3.24 ± 1.81 years after diagnosis, typically of disease-related complications. Only 44% of caregivers reported a helpful conversation with clinicians regarding what to expect at the end of life in DLB. Symptoms commonly worsening prior to death included: cognition and motor function, ADL dependence, behavioral features, daytime sleepiness, communication, appetite, and weight loss. Almost 90% of participants received hospice care, but 20% used hospice for <1 week. Most caregivers reported overall positive experiences in the last month of life, but this was not universal. Having information about DLB and what to expect, access to support, and hospice care were healthcare factors associated with positive and negative end of life experiences. Hospice experiences were driven by communication, care coordination, quality care, and caregiver education. CONCLUSION: Most caregivers of individuals who died with DLB reported positive end-of-life experiences. However, the study identified multiple opportunities for improvement relating to clinician counseling of patients/families, support/hospice referrals, and monitoring individuals with DLB to identify approaching end of life. Future research should quantitatively identify changes that herald end of life in DLB and develop tools that can assist clinicians in evaluating disease stage to better inform counseling and timely hospice referrals. TRIAL REGISTRATION: Trial registration information: NCT04829656.

Continuous sampling of healthy and mastitic quarters of lactating cattle by ultrafiltration after intramammary ceftiofur hydrochloride administration.

BACKGROUND: Pharmacological activity of intramammary drugs depends on adequate drug concentrations within the cistern, but sampling is often limited. Insight into the active drug concentration within the mammary cistern may assist in determining effective and appropriate therapeutic decisions for cows being treated for mastitis. OBJECTIVE: Evaluate the disposition of ceftiofur hydrochloride administered intramammary in diseased and nondiseased quarters. Whole milk and ultrafiltrate sampling techniques were compared. ANIMALS: Ten mature, late lactation Holstein (n = 9) and Jersey (n = 1) dairy cows (422-670 kg) with naturally occurring clinical mastitis, producing between 1.4 and 15.9 kg/day of milk. METHODS: Ultrafiltration probes were placed in both mastitic and healthy quarters. Each quarter was treated with 2 doses of 125 mg ceftiofur hydrochloride suspension, and whole milk and milk ultrafiltrate samples were collected. Ceftiofur concentrations in composite whole milk and milk ultrafiltrate were analyzed. RESULTS: The maximum concentration of ceftiofur was higher in ultrafiltrate samples, but no differences were identified in healthy or mastitic quarters. The use of ultrafiltration probes provides a novel technique for free drug concentrations within the mastitic and healthy bovine mammary gland. CONCLUSIONS AND CLINICAL IMPORTANCE: Significant inter- and intracow variability and lower daily milk weights may overestimate ceftiofur concentrations available within the cistern. The pharmacokinetic (PK) parameters reported in milk ultrafiltrate will help establish a link between the PK and the corresponding drug effect, potentially providing a meaningful rationale for the selection of a safe and effective dose in cows with mastitis.

High-definition transcranial direct current stimulation of the parietal cortices modulates the neural dynamics underlying verbal working memory.

Verbal working memory (vWM) is an essential limited-capacity cognitive system that spans the fronto-parietal network and utilizes the subprocesses of encoding, maintenance, and retrieval. With the recent widespread use of noninvasive brain stimulation techniques, multiple recent studies have examined whether such stimulation may enhance cognitive abilities such as vWM, but the findings to date remain unclear in terms of both behavior and critical brain regions. In the current study, we applied high-definition direct current stimulation to the left and right parietal cortices of 39 healthy adults in three separate sessions (left anodal, right anodal, and sham). Following stimulation, participants completed a vWM task during high-density magnetoencephalography (MEG). Significant neural responses at the sensor-level were imaged using a beamformer and whole-brain ANOVAs were used to identify the specific neuromodulatory effects of the stimulation conditions on neural responses serving distinct phases of vWM. We found that right stimulation had a faciliatory effect relative to left stimulation and sham on theta oscillations during encoding in the right inferior frontal, while the opposite pattern was observed for left supramarginal regions. Stimulation also had a faciliatory effect on theta in occipital regions and alpha in temporal regions regardless of the laterality of stimulation. In summary, our data suggest that parietal HD-tDCS both facilitates and interferes with neural responses underlying both the encoding and maintenance phases of vWM. Future studies are warranted to determine whether specific tDCS parameters can be tuned to accentuate the facilitation responses and attenuate the interfering aspects.

Impact of Prophylactic Cerclage Location on Femoral Fracture Propagation: A Biomechanical Study.

OBJECTIVES: Prophylactic cerclage cables are often placed intraoperatively about a fracture to prevent propagation. However, biomechanical data supporting optimal cable placement location are lacking. The objective of this study was to evaluate the impact of prophylactic cerclage placement location on the propagation of femoral shaft fractures. METHODS: The diaphysis of 14 fresh-frozen cadaveric femora were included. Volumetric bone mineral density in the femoral shaft was obtained from quantitative computed tomography scans. For each specimen, a 5-mm longitudinal fracture was created proximally to simulate a pre-existing fracture. After reaming of the femoral canal, a 3 degrees tapered wedge was advanced with an MTS machine at 0.2 mm/s until failure. The tests were conducted with a CoCr cable placed at varying distances (5 mm, 10 mm, 15 mm, 20 mm, and cableless) from the distal tip of the initial fracture. A compression loadcell was used to measure the cable tension during the tests. The axial force, displacement, and cable tension were monitored for comparison between groups. RESULTS: In the cableless group, the mean force needed to propagate the fracture was 1017.8 ± 450.3 N. With the addition of a cable at 5 mm below the fracture, the failure force nearly doubled to 1970.4 ± 801.1 N (P < 0.001). This also led to significant increases in stiffness (P = 0.006) and total work (P = 0.001) when compared with the control group. By contrast, in the 15 and 20 mm groups, there were no significant changes in the failure force, stiffness, and total work as compared with the control group (P > 0.05). CONCLUSIONS: Propagation of femoral shaft fracture was effectively resisted when a prophylactic cable was placed within 5 mm from the initial fracture, whereas cables placed more than 10 mm below the initial fracture were not effective in preventing fracture propagation.

Orientation of birds in radiofrequency fields in the absence of the Earth's magnetic field: a possible test for the radical pair mechanism of magnetoreception.

The magnetic compass sense of migratory songbirds is thought to derive from magnetically sensitive photochemical reactions in cryptochromes located in photoreceptor cells in the birds' retinas. More specifically, transient radical pairs formed by light-activation of these proteins have been proposed to account for the birds' ability to orient themselves using the Earth's magnetic field and for the observation that radiofrequency magnetic fields, superimposed on the Earth's magnetic field, can disrupt this ability. Here, by means of spin dynamics simulations, we show that it may be possible for the birds to orient in a monochromatic radiofrequency field in the absence of the Earth's magnetic field. If such a behavioural test were successful, it would provide powerful additional evidence for a radical pair mechanism of avian magnetoreception.

The genetics and epidemiology of N- and O-immunoglobulin A glycomics.

BACKGROUND: Immunoglobulin (Ig) glycosylation modulates the immune response and plays a critical role in ageing and diseases. Studies have mainly focused on IgG glycosylation, and little is known about the genetics and epidemiology of IgA glycosylation. METHODS: We generated, using a novel liquid chromatography-mass spectrometry method, the first large-scale IgA glycomics dataset in serum from 2423 twins, encompassing 71 N- and O-glycan species. RESULTS: We showed that, despite the lack of a direct genetic template, glycosylation is highly heritable, and that glycopeptide structures are sex-specific, and undergo substantial changes with ageing. We observe extensive correlations between the IgA and IgG glycomes, and, exploiting the twin design, show that they are predominantly influenced by shared genetic factors. A genome-wide association study identified eight loci associated with both the IgA and IgG glycomes (ST6GAL1, ELL2, B4GALT1, ABCF2, TMEM121, SLC38A10, SMARCB1, and MGAT3) and two novel loci specifically modulating IgA O-glycosylation (C1GALT1 and ST3GAL1). Validation of our findings in an independent cohort of 320 individuals from Qatar showed that the underlying genetic architecture is conserved across ancestries. CONCLUSIONS: Our study delineates the genetic landscape of IgA glycosylation and provides novel potential functional links with the aetiology of complex immune diseases, including genetic factors involved in IgA nephropathy risk.

Non-Invasive Ventilatory Support in Preterm Neonates in the Delivery Room and the Neonatal Intensive Care Unit: A Short Narrative Review of What We Know in 2024.

BACKGROUND: Guidelines recommend non-invasive ventilatory (NIV) support as first-line respiratory support mode in preterm infants as NIV is superior to intubation and mechanical ventilation in preventing death or bronchopulmonary dysplasia. However, with an ever-expanding variety of NIV modes available, there is much debate about which NIV modality should ideally be used, how, and when. The aims of this work were to summarise the evidence on different NIV modalities for both primary and secondary respiratory support: nCPAP, nasal high-flow therapy (nHFT), and nasal intermittent positive airway pressure ventilation (nIPPV), bi-level positive airway pressure (BiPAP), nasal high-frequency oscillatory ventilation (nHFOV), and nasally applied, non-invasive neurally adjusted ventilatory assist (NIV-NAVA) modes, with particular focus on their use in preterm infants. SUMMARY: This is a narrative review with reference to published guidelines by European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. nCPAP is currently the most commonly used primary and secondary NIV modality for premature infants. However, there is increasing evidence on the superiority of nIPPV over nCPAP. No beneficial effect was found for BiPAP over nCPAP. For the use of nHFT, nHFOV, and NIV-NAVA, more studies are needed to establish their place in neonatal respiratory care. KEY MESSAGES: The superiority of nIPPV over nCPAP needs to be confirmed by contemporaneous trials comparing nCPAP to nIPPV at comparable mean airway pressures. Future trials should study NIV modalities in preterm infants with comparable respiratory pathology and indications, at comparable pressure settings and with different modes of synchronisation. Importantly, future trials should not exclude infants of the smallest gestational ages.