Effectiveness of peer-delivered sleep health education and social support in increasing OSA evaluation among at-risk blacks.

To assess the effectiveness of culturally and linguistically tailored, peer-delivered obstructive sleep apnea education and of social support to increase adherence to physician-recommended obstructive sleep apnea evaluation among blacks. In a two-arm randomised controlled trial, we ascertained the effectiveness of peer-delivered obstructive sleep apnea education in increasing obstructive sleep apnea evaluation among 319 blacks at risk of obstructive sleep apnea (intervention = 159 and control = 160); their average age was 47 ± 12.9 years, and 41% were male. Obstructive sleep apnea risk was assessed with the Apnea Risk Evaluation System questionnaire, administered in community venues. Participants in the intervention arm received tailored obstructive sleep apnea education during a 6 month period; those in the control arm received standard sleep and healthy lifestyle information. Analysis focussed on the effectiveness of peer-delivered obstructive sleep apnea education on adherence to obstructive sleep apnea evaluation, but also considered the role of psychosocial factors. The results showed no significant differences in baseline demographic and clinical measures when contrasting participants in the study arms. The adherence rates for home-based obstructive sleep apnea evaluation in the intervention and control arms were 45.9% and 45.6%, respectively. Overall, participants in both study arms (adherers) who underwent obstructive sleep apnea evaluations were likely to experience a greater level of social support (8.2 ± 2.4 vs. 7.3 ± 2.4; p = 0.06). Moreover, adherers showed greater psychosocial scores (i.e., Dysfunctional Beliefs and Attitudes about Sleep scale, Apnea Beliefs Scale (ABS) (and Apnea Knowledge) compared with non-adherers (6.0 ± 1.8 vs. 4.9 ± 2.2; p = 0.02; 77.0 ± 7.1 vs. 73.2 ± 7.4; p = 0.04, and 6.4 ± 3.1 vs. 7.6 ± 2.4; p = 0.06, respectively). The results of the present randomised controlled trial favoured a potential role of peer-based social support and psychosocial factors, associated with obstructive sleep apnea adherence behaviour.

Hyperspectral Visualization-Based Mass Spectrometry Imaging by LMJ-SSP: A Novel Strategy for Rapid Natural Product Profiling in Bacteria.

Mass spectrometry imaging (MSI) has been widely used to discover natural products (NPs) from underexplored microbiological sources. However, the technique is limited by incompatibility with complicated/uneven surface topography and labor-intensive sample preparation, as well as lengthy compound profiling procedures. Here, liquid micro-junction surface sampling probe (LMJ-SSP)-based MSI is used for rapid profiling of natural products from Gram-negative marine bacteria Pseudoalteromonas on nutrient agar media without any sample preparation. A conductance-based autosampling platform with 1 mm spatial resolution and an innovative multivariant analysis-driven method was used to create one hyperspectral image for the sampling area. NP discovery requires general spatial correlation between m/z and colony location but not highly precise spatial resolution. The hyperspectral image was used to annotate different m/z by straightforward color differences without the need to directly interrogate the spectra. To demonstrate the utility of our approach, the rapid analysis of Pseudoalteromonas rubra DSM6842, Pseudoalteromonas tunicata DSM14096, Pseudoalteromonas piscicida JCM20779, and Pseudoalteromonas elyakovii ATCC700519 cultures was directly performed on Agar. Various natural products, including prodiginine and tambjamine analogues, were quickly identified from the hyperspectral image, and the dynamic extracellular environment was shown with compound heatmaps. Hyperspectral visualization-based MSI is an efficient and sensitive strategy for direct and rapid natural product profiling from different Pseudoalteromonas strains.

Eating disorders: When food "Eats" time.

The presence of a physical or mental health issue, such as an eating disorder (ED), impacts daily activities, also known as occupations. For example, an overinvestment in body shape and weight undoubtedly can lead to an underinvestment in other, more meaningful occupations. To address ED-related perceptual disturbances, a detailed log of daily time use can pinpoint food-related occupational imbalances. This study aims to characterize the daily occupations associated with EDs. The first specific objective (SO.1) is to categorize and quantify the temporal organization of a typical day's occupations as self-reported by individuals with an ED. The second specific objective (SO.2) is to compare daily occupational time use among people with different ED types. This retrospective study based on time-use research principles was conducted by analyzing data from an anonymized secondary dataset (Loricorps's Databank). Data were collected between 2016 and 2020, from 106 participants, with descriptive analysis completed to determine the average daily time use for each occupation. A series of one-way analyses of variance (ANOVAs) were performed to compare perceived time use in each occupation for participants with different types of EDs. The outcomes show a marked underinvestment in leisure categories compared to the general population. In addition, personal care and productivity can represent the blind dysfunctional occupations (SO.1). Moreover, compared to those with binge eating disorder (BED), individuals with anorexia nervosa (AN) are significantly more invested in occupations that focus explicitly on perceptual disturbances, such as personal care (SO.2). The highlight of this study is the distinction between marked versus blind dysfunctional occupation, which offers specific avenues for clinical intervention.

Localization of Multiple O-Linked Glycans Exhibited in Isomeric Glycopeptides by Hot Electron Capture Dissociation.

We describe a method to obtain a comprehensive profile of multiple glycosylations in glycopeptide isoforms. We detected a wide range of abundances of various O-glycoforms in isomeric glycopeptides using hot electron capture dissociation (hot ECD) in liquid chromatography-tandem mass spectrometry. To capture low abundant glycosylated species, a prototype of a ZenoTOF 7600 system incorporating an efficient electron-activated dissociation device to perform hot ECD was operated in targeted or scheduled high-resolution multiple reaction monitoring workflows. In addition, Zeno trap pulsing was activated to enhance the sensitivity of the time-of-flight mass spectrometer. Sixty-nine O-glycopeptides of the long O-glycopeptides in tryptic bovine fetuin digest were obtained with a relative abundance range from 100 to 0.2%, which included sialylated glycans with Neu5Ac and Neu5Gc.

Circular Geometry in Molecular Stream Separation to Facilitate Nonorthogonal Field-to-Flow Orientation.

Molecular stream separation (MSS) is a promising complement for continuous-flow synthesis. MSS is driven by forces exerted on molecules by a field applied at an angle to the stream-carrying flow. MSS has only been performed with a 90° field-to-flow angle because of a rectangular geometry of canonic MSS; the second-order rotational symmetry of a rectangle prevents any other angle. Here, we propose a noncanonic circular geometry for MSS, which better aligns with the polar nature of MSS and allows changing the field-to-flow. We conducted in silico and experimental studies of circular geometry for continuous-flow electrophoresis (CFE, an MSS method). We proved two advantages of circular CFE over its rectangular counterpart. First, circular CFE can support better flow and electric-field uniformity than rectangular CFE. Second, the nonorthogonal field-to-flow orientation, achievable in circular CFE, can result in a higher stream resolution than the orthogonal one. Considering that circular CFE devices are not more complex in fabrication than rectangular ones, we foresee that circular CFE will serve as a new standard and a testbed for the investigation and creation of new CFE modalities.

Discontinuously Dewetting Solvent Arrays: Droplet Formation and Poly-Synchronous Surface Extraction for Mass Spectrometry Imaging Applications.

We describe a new liquid tissue stamping method called poly-synchronous surface extraction (PSSE) that utilizes an omniphobic substrate patterned with hydrophilic surface energy traps (SETs), which when wet with a solvent form a dense microdroplet array. When contacted with a tissue sample, each droplet locally extracts analytes from the tissue surface, which subsequentially can be analyzed by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-IMS) or ambient ionization-MS techniques. Optimization of the patterned surface with six different solvents was carried out to increase the droplet density, height, and reproducibility of volume deposition. Once optimized, sister slices of a strawberry (Fragaria × ananassa) were spatially extracted using the PSSE technique and the chemical distribution of selected compounds was analyzed with both MALDI-IMS and a lower resolution but faster ambient liquid microjunction surface sampling probe (LMJ-SSP) approach. Heat maps for target analytes for the PSSE approach are compared to those produced using traditional MALDI-IMS analysis. The PSSE method aligned well with direct analysis and demonstrated the potential to increase the speed of ambient MS tissue imaging techniques by decreasing the number of steps required for sample preparation.

Transient Incomplete Separation of Species with Close Diffusivity to Study the Stability of Affinity Complexes.

Large molecules can be generically separated from small ones, though partially and temporarily, in a pressure-driven flow inside a capillary. This transient incomplete separation has been only applied to species with diffusion coefficients different by at least an order of magnitude. Here, we demonstrate, for the first time, the analytical utility of transient incomplete separation for species with close diffusion coefficients. First, we prove in silico that even a small difference in diffusivity can lead to detectable transient incomplete separation of species. Second, we use computer simulation to prove that such a separation can be used for the reliable determination of equilibrium dissociation constant (Kd) of complexes composed of similar-sized molecules. Finally, we demonstrate experimentally the use of this separation for the accurate determination of Kd value for a protein-aptamer complex. We conclude that "accurate constant via transient incomplete separation" (ACTIS) can serve as a reference method for affinity characterization of protein-aptamer binding in solution.

Protonation-Induced Chirality Drives Separation by Differential Ion Mobility Spectrometry.

Upon development of a workflow to analyze (±)-Verapamil and its metabolites using differential mobility spectrometry (DMS), we noticed that the ionogram of protonated Verapamil consisted of two peaks. This was inconsistent with its metabolites, as each exhibited only a single peak in the respective ionograms. The unique behaviour of Verapamil was attributed to protonation at its tertiary amino moiety, which generated a stereogenic quaternary amine. The introduction of additional chirality upon N-protonation of Verapamil renders four possible stereochemical configurations for the protonated ion: (R,R), (S,S), (R,S), or (S,R). The (R,R)/(S,S) and (R,S)/(S,R) enantiomeric pairs are diastereomeric and thus exhibit unique conformations that are resolvable by linear and differential ion mobility techniques. Protonation-induced chirality appears to be a general phenomenon, as N-protonation of 12 additional chiral amines generated diastereomers that were readily resolved by DMS.

Template Instrumentation for "Accurate Constant via Transient Incomplete Separation".

Accurate Constant via Transient Incomplete Separation (ACTIS) is a new method for finding the equilibrium dissociation constant Kd of a protein-small molecule complex based on transient incomplete separation of the complex from the unbound small molecule in a capillary. This separation is caused by differential transverse diffusion of the complex and the small molecule in a pressure-driven flow. The advection-diffusion processes underlying ACTIS can be described by a system of partial differential equations allowing for a virtual ACTIS instrument to be built and ACTIS to be studied in silico. The previous in silico studies show that large variations in the fluidic system geometry do not affect the accuracy of Kd determination, thus, proving that ACTIS is conceptually accurate. The conceptual accuracy does not preclude, however, instrumental inaccuracy caused by run-to-run signal drifts. Here we report on assembling a physical ACTIS instrument with a fluidic system that mimics the virtual one and proving the absence of signal drifts. Furthermore, we confirmed method ruggedness by assembling a second ACTIS instrument and comparing the results of experiments performed with both instruments in parallel. Despite some unintentional differences between the instruments (caused by tolerances in sizes, positions, etc.) and noticeable differences in their respective separagrams, we found that the Kd values determined for identical samples with these instruments were equal. Conclusively, the fluidic system presented here can serve as a template for reliable ACTIS instrumentation.

Association between extremely preterm caesarean delivery and maternal depressive and anxious symptoms: a national population-based cohort study.

OBJECTIVE: To evaluate whether caesarean delivery before 26 weeks of gestation was associated with symptoms of depression and anxiety in mothers in comparison with deliveries between 26 and 34 weeks. DESIGN: Prospective national population-based EPIPAGE-2 cohort study. SETTING: 268 neonatology departments in France, March to December 2011. POPULATION: Mothers who delivered between 22 and 34 weeks and whose self-reported symptoms of depression (Center for Epidemiologic Studies Depression Scale: CES-D) and anxiety (State-Trait Anxiety Inventory: STAI) were assessed at the moment of neonatal discharge. METHODS: The association of caesarean delivery before 26 weeks with severe symptoms of depression (CES-D ≥16) and anxiety (STAI ≥45) was assessed by weighted and design-based log-linear regression model. MAIN OUTCOME MEASURES: Severe symptoms of depression and anxiety in mothers of preterm infants. RESULTS: Among the 2270 women completing CES-D and STAI questionnaires at the time of neonatal discharge, severe symptoms of depression occurred in 25 (65.8%) women having a caesarean before 26 weeks versus in 748 (50.6%) women having a caesarean after 26 weeks. Caesarean delivery before 26 weeks was associated with severe symptoms of depression compared with caesarean delivery after 26 weeks (adjusted relative risk [aRR] 1.42, 95% CI 1.12-1.81) adjusted to neonatal birthweight and severe neonatal morbidity among other factors. There was no evidence of an association between mode of delivery and symptoms of anxiety. CONCLUSIONS: Mothers having a caesarean delivery before 26 weeks' gestation are at high risk of symptoms of depression and may benefit from specific preventive care. TWEETABLE ABSTRACT: Mothers having caesarean delivery before 26 weeks' gestation are at high risk of symptoms of depression.

The impact of chorionicity on pregnancy outcome and neurodevelopment at 2 years old among twins born preterm: the EPIPAGE-2 cohort study.

OBJECTIVE: To compare the short- and mid-term outcomes of preterm twins by chorionicity of pregnancy. DESIGN: Prospective nationwide population-based EPIPAGE-2 cohort study. SETTING: 546 maternity units in France, between March and December 2011. POPULATION: A total of 1700 twin neonates born between 24 and 34 weeks of gestation. METHODS: The association of chorionicity with outcomes was analysed using multivariate regression models. MAIN OUTCOME MEASURES: First, survival at 2-year corrected age with or without neurosensory impairment, and second, perinatal, short-, and mid-term outcomes (survival at discharge, survival at discharge without severe morbidity) were described and compared by chorionicity. RESULTS: In the EPIPAGE 2 cohort, 1700 preterm births were included (850 twin pregnancies). In all, 1220 (71.8%) were from dichorionic (DC) pregnancies and 480 from monochorionic (MC) pregnancies. MC pregnancies had three times more medical terminations than DC pregnancies (1.67 versus 0.51%, P < 0.001), whereas there were three times more stillbirths in MC than in DC pregnancies (10.09 versus 3.78%, P < 0.001). Both twins were alive at birth in 86.6% of DC pregnancies compared with 80.0% among MC pregnancies (P = 0.008). No significant difference according to chorionicity was found regarding neonatal deaths and morbidities. Likewise, for children born earlier than 32 weeks, the 2-year follow-up neurodevelopmental results were not significantly different between DC and MC twins. CONCLUSIONS: This study confirms that MC pregnancies have a higher risk of adverse outcomes. However, the outcomes among preterm twins admitted to neonatal intensive care units are similar irrespective of chorionicity. TWEETABLE ABSTRACT: Monochorionicity is associated with adverse perinatal outcomes, but outcomes for preterm twins are comparable irrespective of their chorionicity.

Electronic spectroscopy of differential mobility-selected prototropic isomers of protonated para-aminobenzoic acid.

para-Aminobenzoic acid (PABA) was electrosprayed from mixtures of protic and aprotic solvents, leading to formation of two prototropic isomers in the gas phase whose relative populations depended on the composition of the electrospray solvent. The two ion populations were separated in the gas phase using differential mobility spectrometry (DMS) within a nitrogen-only environment at atmospheric pressure. Under high-field conditions, the two prototropic isomers eluted with baseline signal separation with the N-protonated isomer having a more negative CV shift than the O-protonated isomer, in accord with previous DMS studies. The conditions most favorable for formation and separation of each tautomer were used to trap each prototropic isomer in a quadrupole ion trap for photodissociation action spectroscopy experiments. Spectral interrogation of each prototropic isomer in the UV region (3-6 eV) showed good agreement with previously recorded spectra, although a previously reported band (4.8-5.4 eV) was less intense for the O-protonated isomer in our measured spectrum. Without DMS selection, the measured spectra contained features corresponding to both protonated isomers even when solvent conditions were optimised for formation of a single isomer. Interconversion between protonated isomers within the ion trap was observed when protic ESI solvents were employed, leading to spectral cross contamination even with mobility selection. CCSD vertical excitation energies and vertical gradient (VG) Franck-Condon simulations are presented and reproduce the measured spectral features with near-quantitative agreement, providing supporting evidence for spectral assignments.

UVPD spectroscopy of differential mobility-selected prototropic isomers of protonated adenine.

Two prototropic isomers of adenine are formed in an electrospray ion source and are resolved spatially in a differential mobility spectrometer before detection in a triple quadrupole mass spectrometer. Each isomer is gated in CV space before being trapped in the linear ion trap of the modified mass spectrometer, where they are irradiated by the tuneable output of an optical parametric oscillator and undergo photodissociation to form charged fragments with m/z 119, 109, and 94. The photon-normalised intensity of each fragmentation channel is measured and the action spectra for each DMS-gated tautomer are obtained. Our analysis of the action spectra, aided by calculated vibronic spectra and thermochemical data, allow us to assign the two signals in our measured ionograms to specific tautomers of protonated adenine.

UVPD Spectroscopy of Differential Mobility-Selected Prototropic Isomers of Rivaroxaban.

Two ion populations of protonated Rivaroxaban, [C19H18ClN3O5S + H]+, are separated under pure N2 conditions using differential mobility spectrometry prior to characterization in a hybrid triple quadrupole linear ion trap mass spectrometer. These populations are attributed to bare protonated Rivaroxaban and to a proton-bound Rivaroxaban-ammonia complex, which dissociates prior to mass-selecting the parent ion. Ultraviolet photodissociation (UVPD) and collision-induced dissociation (CID) studies indicate that both protonated Rivaroxaban ion populations are comprised of the computed global minimum prototropic isomer. Two ion populations are also observed when the collision environment is modified with 1.5% (v/v) acetonitrile. In this case, the protonated Rivaroxaban ion populations are produced by the dissociation of the ammonium complex and by the dissociation of a proton-bound Rivaroxaban-acetonitrile complex prior to mass selection. Again, both populations exhibit a similar CID behavior; however, UVPD spectra indicate that the two ion populations are associated with different prototropic isomers. The experimentally acquired spectra are compared with computed spectra and are assigned to two prototropic isomers that exhibit proton sharing between distal oxygen centers.

Streamlined Development of Targeted Mass Spectrometry-Based Method Combining Scout-MRM and a Web-Based Tool Indexed with Scout Peptides.

MS-based targeted proteomics is a relevant technology for sensitive and robust relative or absolute quantification of proteins biomarker candidates in complex human biofluids or tissue extracts. Performing a multiplex assay imposes time scheduling of peptide monitoring only around their expected retention time that needs to be defined with synthetic peptide. Time-scheduled monitoring is clearly a constraint that precludes from straightforward assay transfer between biological matrices or distinct experimental setup. Any unexpected retention time (RT) shift challenges assay robustness and its implementation for large-scale analysis. Recently, Scout-multiple reaction monitoring that fully releases multiplexed targeted acquisition from RT scheduling by successively monitoring complex transition groups triggered with sentinel molecules called Scout has been introduced. It is herein documented how Peptide Selector database and tool streamlines the building of a multiplexed method thanks to RT indexation relative to Scout peptides. This case study deals with surrogate peptides of biomarker candidates related to drug-induced liver and vascular injury, running such on-line built method (eight Scouts triggering the monitoring of a total of 692 transitions) enables 100% recovery of a panel of 93 spiked-in heavy labeled standards, despite significant RT shifts between serum, plasma, or urine. This result illustrates the simplicity of automatically building and deploying robust proteomics targeted assay.

Separating Isomers, Conformers, and Analogues of Cyclosporin using Differential Mobility Spectroscopy, Mass Spectrometry, and Hydrogen-Deuterium Exchange.

Cyclosporins are an invaluable class of drug used to prevent the rejection of transplanted tissue. While the most popular drug in this group is cyclosporin A, several other analogues are available, including some enantiomeric and structurally isomeric forms. Unfortunately, the presence of such isomers can make the detection and identification of these drugs by mass spectrometry (MS) alone quite challenging. Here, we demonstrate the separation and analysis of six cyclosporin analogues using liquid chromatography (LC) and differential mobility spectroscopy (DMS) coupled to MS. Using DMS, we demonstrate the separation of three isomers: CycA and CycH (cyclosporin H), which are enantiomers, and isocyclosporin A (a structural isomer of CycA and CycH). For several of the cyclosporins, we can separate different conformers for each isomeric form. After DMS separation, tandem mass spectrometry (MS/MS) analyses of the separated isomers also distinguish these isomeric forms of cyclosporin. In addition, we have probed differences between each isomer by using gas-phase hydrogen-deuterium exchange (HDX) immediately after DMS separation, which reveals differences in the levels of intramolecular hydrogen bonding between each of the cyclosporins.

Assessing Accuracy of an Analytical Method In Silico: Application to "Accurate Constant via Transient Incomplete Separation" (ACTIS).

Analytical methods may not have reference standards required for testing their accuracy. We postulate that the accuracy of an analytical method can be assessed in the absence of reference standards in silico if the method is built upon deterministic processes. A deterministic process can be precisely computer-simulated, thus allowing virtual experiments with virtual reference standards. Here, we apply this in silico approach to study "Accurate Constant via Transient Incomplete Separation" (ACTIS), a method for finding the equilibrium dissociation constant (Kd) of protein-small-molecule complexes. ACTIS is based on a deterministic process: molecular diffusion of the interacting protein-small-molecule pair in a laminar pipe flow. We used COMSOL software to construct a virtual ACTIS setup with a fluidic system mimicking that of a physical ACTIS instrument. Virtual ACTIS experiments performed with virtual samples-mixtures of a protein and a small molecule with defined rate constants and, thus, Kd of their interaction-allowed us to assess ACTIS accuracy by comparing the determined Kd value to the input Kd value. Further, the influence of multiple system parameters on ACTIS accuracy was investigated. Within multifold ranges of parameter values, the values of Kd did not deviate from the input Kd values by more than a factor of 1.25, strongly suggesting that ACTIS is intrinsically accurate and that its accuracy is robust. Accordingly, further development of ACTIS can focus on achieving high reproducibility and precision. We foresee that in silico accuracy assessment, demonstrated here with ACTIS, will be applicable to other analytical methods built upon deterministic processes.

rPTMDetermine: A Fully Automated Methodology for Endogenous Tyrosine Nitration Validation, Site-Localization, and Beyond.

We present herein rPTMDetermine, an adaptive and fully automated methodology for validation of the identification of rarely occurring post-translational modifications (PTMs), using a semisupervised approach with a linear discriminant analysis (LDA) algorithm. With this strategy, verification is enhanced through similarity scoring of tandem mass spectrometry (MS/MS) comparisons between modified peptides and their unmodified analogues. We applied rPTMDetermine to (1) perform fully automated validation steps for modified peptides identified from an in silico database and (2) retrieve potential yet-to-be-identified modified peptides from raw data (that had been missed through conventional database searches). In part (1), 99 of 125 3-nitrotyrosyl-containing (nitrated) peptides obtained from a ProteinPilot search were validated and localized. Twenty nitrated peptides were falsely assigned because of incorrect monoisotopic peak assignments, leading to erroneous identification of deamidation and nitration. Five additional nitrated peptides were, however, validated after performing nonmonoisotopic peak correction. In part (2), an additional 236 unique nitrated peptides were retrieved and localized, containing 113 previously unreported nitration sites; 25 endogenous nitrated peptides with novel sites were selected and verified by comparison with synthetic analogues. In summary, we identified and confidently validated 296 unique nitrated peptides-collectively representing the largest number of endogenously identified 3-nitrotyrosyl-containing peptides from the cerebral cortex proteome of a Macaca fascicularis model of stroke. Furthermore, we harnessed the rPTMDetermine strategy to complement conventional database searching and enhance the confidence of assigning rarely occurring PTMs, while recovering many missed peptides. In a final demonstration, we successfully extended the application of rPTMDetermine to peptides featuring tryptophan oxidation.

[Polymorphism and differential diagnosis of neonatal lupus erythematosus]. / Polymorphisme et diagnostics différentiels du lupus érythémateux néonatal.

INTRODUCTION: Neonatal lupus erythematosus (NEL) is a rare condition secondary to transplacental transfer of maternal anti-nuclear antibodies, generally anti-Ro/SSA. The most common signs are dermatological and cardiac. The most frequently reported clinical association is periorbital erythema, known as "owl eye", and bipolar erythematous maculopapular plaques with fine scales. However, many semiological variants can result in diagnostic errors or delays. PATIENTS AND METHODS: This was a single-centre retrospective observational study collating all cases of NEL seen at paediatric dermatology consultations between 2010 and 2018. The diagnosis of NEL was confirmed by the presence of specific antinuclear antibodies (ANA) in the mother. The aim was to describe the different clinical forms of NEL and to discuss differential diagnosis. RESULTS AND DISCUSSION: We identified ten cases of NEL, all addressed without diagnosis or with misdiagnosis. They were divided into 3 groups based on the semiology of skin lesions: 5 presented inflammatory macular papules on the cephalic extremity and head; 3 presented acquired periorbital depigmentation; 2 presented atrophic and diffuse livedoid lesions. None had heart disease and associated haematological and hepatic damage was mild. Spontaneous remission was seen in all cases before the age of 6 months. The mothers, who were generally symptom-free or paucisymptomatic, presented anti-Ro/SSA NAAs. CONCLUSION: Recognition of the different clinical forms of NEL enables early institution of suitable therapy and monitoring of subsequent pregnancies.

Enhancing signal and mitigating up-front peptide fragmentation using controlled clustering by gas-phase modifiers.

Up-front CID fragmentation is a phenomenon where molecular ions are activated and fragment as they enter the atmosphere-to-vacuum region of the mass spectrometer, and consequently can complicate the mass spectra and their analysis. This phenomenon can be minimized by controlling the voltages on lens/optic elements where ions are sampled from the atmospheric region, but this approach can also have a negative effect on overall ion sensitivity. In this study, we introduce gas-phase modifiers (acetonitrile, acetone, cyclohexane, water, and methanol) to the curtain gas to mitigate up-front CID fragmentation. These modifiers cluster with incoming ions, increasing the energy barrier to fragmentation and consequently reducing the complexity of mass spectra. The clustering is monitored by differential mobility spectrometry-mass spectrometry (DMS-MS) and precursor mass spectrum-scanning. Unlike typical singly charged species, peptide ion-modifier clusters were found to survive through the atmosphere-to-vacuum interface of the mass spectrometer, showing that highly charged peptides cluster most strongly with acetonitrile and acetone. In addition, when peptides cluster with acetonitrile, they produce a large increase in signal intensity for the most highly charged and fragile ions. This results in a significant reduction, up to 90% with some modifiers, in up-front CID fragmentation for these fragile highly charged peptides, increasing the overall analytical sensitivity and decreasing the limits of detection by up to 82% depending on the analyte. The proposed technique has no significant detrimental effect on the peptide mass fingerprinting of a BSA or mAb protein digest, but it does reduce the amount of redundant and data-deficient spectra needed to produce adequate sequence coverage using information-dependent acquisition methods by ~ 40%. We propose that this technique could have a benefit in the fields of proteomics and peptidomics where up-front CID fragmentation and chemical noise routinely mask targets of biological importance. Graphical abstract.