High-Definition Differential Ion Mobility Spectrometry with Structural Isotopic Shifts for Anionic Compounds.

Differential ion mobility spectrometry (FAIMS) had emerged in the 2000s as a novel tool for postionization separations in conjunction with mass spectrometry (MS). High-definition FAIMS introduced a decade ago has enabled resolution of peptide, lipid, and other molecular isomers with minute structural variations and recently the isotopic shift analyses where the spectral pattern for stable isotopes fingerprints the ion geometry. Those studies, including all isotopic shift analyses, were in the positive mode. Here, we achieve the same high resolution for anions exemplified by phthalic acid isomers. The resolving power and magnitude of isotopic shifts are in line with the metrics for analogous haloaniline cations, establishing high-definition negative-mode FAIMS with structurally specific isotopic shifts. Different shifts (including the new 18O) remain additive and mutually orthogonal, demonstrating the generality of those properties across the elements and charge states. Expanding to common (not halogenated) organic compounds is a key step toward the broad use of FAIMS isotopic shift methodology.

High-Definition Ion Mobility/Mass Spectrometry with Structural Isotopic Shifts for Nominally Isobaric Isotopologues.

We had reported the isotopic envelopes in differential IMS (FAIMS) separations depending on the ion structure. However, this new approach to distinguish isomers was constrained by the unit-mass resolution commingling all nominally isobaric isotopologues. Here, we directly couple high-definition FAIMS to ultrahigh-resolution (Orbitrap) MS and employ the resulting platform to explore the FAIMS spectra for isotopic fine structure. The peak shifts therein for isotopologues of halogenated anilines with 15N and 13C (split by 6 mDa) in N2/CO2 buffers dramatically differ, more than for the 13C, 37Cl, or 81Br species apart by 1 or 2 Da. The shifts in FAIMS space upon different elemental isotopic substitutions are orthogonal mutually and to the underlying separations, forming fingerprint multidimensional matrices and 3-D trajectories across gas compositions that redundantly delineate all isomers considered. The interlocking instrumental and methodological upgrades in this work take the structural isotopic shift approach to the next level.

Immediate Fetal Outcome in Deliveries with Meconium Stained Amniotic Fluid.

BACKGROUND: Meconium-stained amniotic fluid is considered as the bad predictor of fetal outcome having significant perinatal morbidity and mortality. This study aimed to compare immediate fetal outcomes in meconium-stained amniotic fluid and clear amniotic fluid. METHODS: Hospital-based comparative observational study was conducted from a total of 204 women admitted in labour room at a tertiary level hospital. Among them, 102 were cases with meconium-stained amniotic fluid, and 102 were comparison groups with clear amniotic fluid. Fetal outcome was compared between these two groups. RESULTS: The study findings revealed that majority (74.5%) in the study group had cesarean section as compared to 14.7% in the comparative group. More than one-fourth (26.5%) of the newborns in the study group had moderate to severe birth asphyxia, needed resuscitation (25.5%) and neonatal intensive care unit admission (25.5%) as compared to 3.9% from the comparative group. Maternal age (COR=0.34, 95%CI=0.15-0.81), color of amniotic fluid (COR=0.11; 95%CI=0.04-0.33), meconium consistency (COR=0.27; 95%CI=0.17-0.43), and mode of delivery (COR=0.36; 95%CI=0.17-0.79) were associated with birth asphyxia in bivariate analysis. Maternal age (AOR=2.66; 95%CI=1.04-6.81) and color of amniotic fluid (AOR=11.50; 95%CI=2.97-44.56) were associated with birth asphyxia in the multivariate analysis. CONCLUSIONS: Meconium-stained amniotic fluid was associated with increased frequency of cesarean section and adverse fetal outcome with birth asphyxia being the major complications compared with clear amniotic fluid. Predictors of birth asphyxia were maternal age and color of amniotic fluid.

Assessing the Dipole Moments and Directional Cross Sections of Proteins and Complexes by Differential Ion Mobility Spectrometry.

Ion mobility spectrometry (IMS) has become a mainstream approach to fractionate complex mixtures, separate isomers, and assign the molecular geometries. All modalities were grouped into linear IMS (based on the absolute ion mobility, K) and field asymmetric waveform IMS (FAIMS) relying on the evolution of K at a high normalized electric field (E/N) that induces strong ion heating. In the recently demonstrated low-field differential (LOD) IMS, the field is too weak for significant heating but locks the macromolecular dipoles to produce novel separations controlled by the relevant directional collision cross sections (CCSs). Here, we show LODIMS for mass-selected species, exploring the dipole alignment across charge states for the monomers and dimers of an exemplary protein, the alcohol dehydrogenase. Distinct conformational families for aligned species are revealed with directional CCS estimated from the field-dependent trend lines. We set up a model to extract the fractions of pendular conformers as a function of field intensity and translate them into dipole moment distributions. These developments make a critical step toward establishing LODIMS as a new tool for top-down proteomics and integrative structural biology.

Determinants of Uptake of Cervical Cancer Screening among Women Attending Tertiary Level Hospital.

BACKGROUND: Cervical cancer, being the fourth commonest cancer in women worldwide, is also the most frequent cause of cancer deaths among women in developing and underdeveloped countries. Screening is the gold standard to control the disease yet, its uptake is still very low among Nepalese women. Thus, the objective of this study was to find out the determinants of uptake of cervical cancer screening among women. METHODS: Data were collected from a total of 220 women visiting gynecology outpatient department of Tribhuvan University Teaching Hospital, Kathmandu by using non-probability purposive sampling technique. Descriptive statistics and binary logistic regression analysis were applied. RESULTS: The study findings revealed that the prevalence of uptake of cervical cancer screening was about one third (38.6%). Educational qualification had a significant association with the uptake of cervical cancer screening (p=0.017). Women's age (COR=0.267; 95%CI=0.150-0.475), knowledge on availability of health services (COR=5.310; 95% CI=2.947-9.567), awareness on cost of screening services (COR=26.329; 95% CI=12.704-54.566), and knowledge level (COR=2.677; 95%CI= 1.385-5.173) had a significant association with the uptake of cervical cancer screening in bivariate analysis. Age (AOR=0.148; 95%CI=0.058-0.375) and awareness on cost of screening services (AOR=61.048, 95%CI=19.194-194.175) were found as major determinants of uptake of cervical cancer screening. CONCLUSIONS: The findings of this study conclude that the prevalence of uptake of cervical cancer screening was below half. Determinants of uptake of cervical cancer screening were age and awareness on the cost of screening services. So, awareness campaigns about cervical cancer screening are very necessary to increase its uptake and to reduce the morbidity and mortality associated with it.

Delineation of Isomers by the 13C Shifts in Ion Mobility Spectra.

Mass spectrometry (MS) and isotopes were intertwined for a century, with stable isotopes central to many MS identification and quantification protocols. In contrast, the analytical separations including ion mobility spectrometry (IMS) largely ignored isotopes, partly because of insufficient resolution. We recently delineated various halogenated aniline isomers by structurally specific splitting in FAIMS spectra. While this capability hinges on the 13C shifts, all preceding studies leveraged 37Cl or 81Br to enhance the differentiation. However, such abundant heavy isotopes are absent from typical organic compounds. With single I isotope, iodinated organics generate similar isotopic envelopes dominated by the 13C atoms. Here, we distinguish the three monoiodoaniline isomers based on the shifts solely for one or two 13C atoms. The differentiation may be somewhat improved using multipoint peak position descriptions for more reproducible shifts. The interisomer order of shifts differs from those for chlorinated or brominated analogues, showcasing the specificity of approach. We also investigated the mass scaling of isotopic shifts, encountering divergent trends for different structural families.

Low-Field Differential Ion Mobility Spectrometry of Dipole-Aligned Macromolecules.

Ion mobility spectrometry (IMS) with mass spectrometry has grown into a powerful approach to simplify complex mixtures, disentangle isomers, and elucidate their geometries. Two established branches are linear IMS based on the absolute mobility K at moderate normalized electric field E/N and field asymmetric waveform IMS (FAIMS) relying on the evolution of K at high E/N causing strong ion heating. Here, we introduce low-field differential IMS (LODIMS), where the field is too weak for significant heating but suffices to lock the permanent macromolecular ion dipoles, producing novel separations based solely on their alignment. The method is demonstrated for a prototypical large protein-albumin. Its oligomers start separating at fields of just 1 kV/cm (4 Td), or ∼5% of those typical for FAIMS. Negligible ion heating at such fields allows preserving fragile species, in particular the noncovalent complexes up to pentamers (332 kDa) destroyed in FAIMS and not detected without it. The separation parameter (compensation field, EC) in this regime scales with the field linearly versus cubically in FAIMS. The dipole moments obtained from threshold fields for alignment and directional cross sections estimated from the slope of said linear EC dependence appear reasonable.

Structurally Informative Isotopic Shifts in Ion Mobility Spectra for Heavier Species.

The isotopic molecular envelopes due to stable isotopes for most elements were a staple of mass spectrometry since its origins, often leveraged to identify and quantify compounds. However, all isomers share one MS envelope. As the molecular motion in media also depends on the isotopic composition, separations such as liquid chromatography (LC) and ion mobility spectrometry (IMS) must also feature isotopic envelopes. These were largely not observed because of limited resolution, except for the (structurally uninformative) shifts in LC upon H/D exchange. We recently found the isotopic shifts in FAIMS for small haloanilines (∼130-170 Da) to hinge on the halogen position, opening a novel route to isomer characterization. Here, we extend the capability to heavier species: dibromoanilines (DBAs, ∼250 Da) and tribromoanilines (TBAs, ∼330 Da). The 13C shifts for DBAs and TBAs vary across isomers, some changing sign. While 81Br shifts are less specific, the 2-D 13C/81Br shifts unequivocally differentiate all isomers. The trends for DBAs track those for dichloroanilines, with the 13C shift order preserved for most isomers. The peak broadening due to merged isotopomers is also isomer-specific. The absolute shifts for TBAs are smaller than those for lighter haloanilines, but differentiate isomers as well because of compressed uncertainties. These results showcase the feasibility of broadly distinguishing isomers in the more topical ∼200-300 Da range using the isotopic shifts in IMS spectra.

Perception of Women regarding Respectful Maternity Care during Facility-Based Childbirth.

BACKGROUND: Respectful care during childbirth has been described as "a universal human right that encompasses the principles of ethics and respect for women's feelings, dignity, choices, and preferences." Many women experience a lack of respectful and abusive care during childbirth across the globe. OBJECTIVE: This study aimed to determine women's perception of respectful maternity care (RMC) during facility-based childbirth. METHOD: A descriptive cross-sectional study was conducted among 150 mothers admitted to the maternity ward of Nepal Medical College and Teaching Hospital using a purposive sampling technique. Data were collected through an interview technique by using a validated tool containing 15 items each measured on a scale of 5. Statistical Package for Social Science (SPSS) version 16 was used for data analysis. Frequency, percentage, mean score, standard deviation, chi-square test, and binary logistic regression were used to analyze descriptive and inferential statistics. RESULTS: In total, 84.7% of the women reported that they have experienced overall RMC services with a mean score ± SD (61.70 ± 12.12). Though the majority of the women reported that they have experienced RMC services, they also revealed that they have experienced disrespectful care in various forms such as being shouted upon (30.0%), being slapped (18.7%), delayed service provision (22.7%), and not talking positively about pain and relief during childbirth (28.0%). Likewise, length of stay, parity, and time of delivery were found as factors that influenced friendly care (COR = 0.383, 95% CI: 0.157-0.934), abuse-free care (COR = 3.663, 95% CI: 1.607-8.349), and timely care (COR = 2.050, 95% CI: 1.031-4.076) dimensions of RMC, respectively. CONCLUSION: Even though RMC emphasizes eliminating disrespectful and abusive environment from health facilities, 15.0% of participants perceived that they have not experienced overall RMC services. So, the health facility should focus on the interventions which ensure that every woman receives this basic human dignity during one of the most vulnerable times in their lives.

High-Resolution Ion Mobility Separations of Isomeric Glycoforms with Variations on the Peptide and Glycan Levels.

Glycosylation is a ubiquitous post-translational modification (PTM) that strongly affects the protein folding and function. Glycosylation patterns are impacted by many diseases, making promising biomarkers. Glycans are also the most complex PTMs, exhibiting isomers (linkage, anomers, and those with isomeric moieties). Permuted with localization variants that occur for all PTMs, these produce numerous isomeric glycoforms. Characterizing them by mass spectrometry and ion mobility spectrometry (IMS) has been a challenge. High-definition differential IMS (FAIMS) had robustly disentangled isomeric peptides involving other PTMs but was not evaluated for glycopeptides that featured multilevel isomerism. Here, we apply it to representative mucin glycopeptides with O-linked glycans: three GalNAc localization variants, a pair with α/ß GalNAc anomers, and another with GalNAc/GlcNAc isomers. The first two classes were separated baseline with the resolution exceeding previous benchmarks by 10-fold, and the last pair was partly resolved. The recently demonstrated straightforward coupling to ultrahigh-resolution MS and electron-transfer dissociation makes high-definition FAIMS an attractive tool for glycoproteomics.

Effect of ethanolic extract of Melia dubia leaves on full-thickness cutaneous wounds in Wistar rats.

In recent years, the therapeutic effects of phyto-principles have been appreciated for their promising effects on wound healing. Melia dubia (Malabar neem) possesses anti-cancer, anti-diabetic, anti-tumor, anti-inflammatory, antioxidant, antibacterial, and fungicidal properties. Here, we studied the wound healing efficacy of ethanolic extract of M. dubia leaves on cutaneous wound healing for the first time. The ethanolic extract of M. dubia was applied topically on the wounds of the experimental rats until the wounds heal completely. Wounds of the control rats were treated with PBS. Granulation tissues formed on wound surfaces of the excision wound were harvested on days 4 and 8 and analyzed to determine the total collagen and hexosamine content. Total collagen and hexosamine were significantly (p < .001) higher in M. dubia treated rats compared to control. The rate of wound closure was significantly higher (p < .001) and period of epithelialization was shorter in M. dubia treated rats. Incision wound tissue was used for the tensile strength measurement. Tensile strength was improved in M. dubia treated wound tissues. Results concluded that the topical application of ethanolic extracts of M. dubia improved the rate of wound contraction and tensile strength by increased synthesis of collagen.

Elemental Dependence of Structurally Specific Isotopic Shifts in High-Field Ion Mobility Spectra.

Nearly all molecules incorporate at least one element with stable isotopes, yielding ubiquitous isotopologic envelopes in mass spectra. Those envelopes split in differential or field asymmetric waveform ion mobility (FAIMS) spectra depending on the ion geometry, enabling a new general approach to isomer delineation as we demonstrated for chloroanilines. Here, we report that analogous bromoanilines exhibit qualitatively distinct isotopic shifts under identical conditions, some changing signs depending on the gas. This dramatic elemental specificity conveys the breadth and diversity of structural isotopic effect in FAIMS, suggesting unique information-rich patterns for compounds involving various elements and feasibility of enhancing the structural elucidation by atom substitution. We also introduce the capability to make or ensure structural assignments employing major isomer-specific peak broadening due to unresolved isotopomer mixtures.

Identification of Isomers by Multidimensional Isotopic Shifts in High-Field Ion Mobility Spectra.

Nearly all molecules incorporate elements with stable isotopes. The resulting isotopologue envelopes in mass spectra tell the exact stoichiometry but nothing about the geometry. Chromatography and electrophoresis at high resolution also can distinguish isotopologues, again without revealing structural information. In high-definition differential ion mobility (FAIMS) spectra, these envelopes universally split in a structure-specific manner, providing a new general approach to isomer delineation. Here, we show that the peak shifts from instances of the same isotope are equal and can be averaged into characteristic elemental shifts, namely 13C and 37Cl for dichloroanilines (DCA). Matrices of these shifts, including the gas composition dimension, are unique to the structure. Hence, all six DCA isomers (with four making two unresolved pairs) are readily delineated in the 13C/37Cl maps with He/CO2 buffer gases. Mixtures of coeluting isomers are also distinguished from pure components.

Factors Associated with the Utilization of Institutional Delivery Service among Mothers.

BACKGROUND: Assessment of utilization of institutional delivery services is crucial to reduce risk of maternal mortality and morbidity in countries like Nepal. This study was conducted to find out the proportion of utilization of institutional delivery service and associated factors among mothers. METHODS: Data was collected from the total of 129 mothers of Kathar VDC, Chitwan district who delivered baby within last one year proceeding the period of data collection using census method. Descriptive statistics and binary logistic regression analysis were applied. RESULTS: Out of 129 mothers, 78.3% had their delivery in the health facilities. Binary logistic analysis showed number of factors associated with utilization of institutional delivery service such as ethnicity, respondents educational level, number of pregnancy, number of ANC visit and birth preparedness status. But in the multivariable logistic regression analysis, no. of ANC visit (AOR = 10.03, 95 % CI = 1.02-98.29) was only independent factors affecting institutional delivery service utilization. CONCLUSIONS: A number of factors have been shown to affect the utilization of institutional delivery. Therefore, concerned authority should plan and implement awareness programme aiming at increasing antenatal clinic visits and utilization of institutional delivery service.