Ion-Ion and Ion-Molecule Reactions at the Surface of Proteins Produced by Nanospray. Information on the Number of Acidic Residues and Control of the Number of Ionized Acidic and Basic Residues

Mass Spectra of charge states of folded proteins were obtained with nanospray and aqueous solution containing 20 μM the protein (ubiquitin, cytochrome c, lysozyme) and one of the NaA salts NaCl, NaI, NaAc (acetate) (1–10 mM). At very low collision activated decomposition (CAD), the mass spectra of a protein with charge z exhibited a replacement of zH+ with zNa+ and also multiple adducts of NaA. Higher CAD converts the NaA adduct peaks to Na minus H peaks. These must be due to loss of HA where the H was provided by the protein. The degree of HA loss with increasing CAD followed the order I < Cl < Ac. Significantly, the intensity of the ions with n (Na minus H) adducts showed a downward break past an nMAX which is equal to the number of acidic residues of the protein plus the charge of the protein. All the observations could be rationalized within the framework of the electrospray mechanism and the charge residue model, which predict that due to extensive evaporation of solvent, the solutes will reach very high concentrations in the final charged droplets. At such high concentrations, positive ions such as Na+, NH4+ form ion pairs with ionized acidic residues and the negative A− form ion pairs with ionized basic residues of the protein. Adducts of Na+, and NaA to backbone amide groups occur also. This reaction mechanism fits all the experimental observations and provides predictions that the number of acidic and basic groups at the surface of the gaseous protein that remain ionized can be controlled by the absence or presence of additives to the solution

Prevalence and independent risk factors for hearing loss in NICU infants

Aim: To determine the prevalence and independent relationship between hearing loss and risk factors in a representative neonatal intensive care unit (NICU) population. Methods: Automated auditory brainstem response (AABR) hearing screening has been introduced since 1998 in the Dutch NICUs. After a second AABR failure, diagnostic ABR was used to establish diagnosis of hearing loss. Newborns who died before the age of 3 months were excluded. In the present study only the NICU infants who were born with a gestational age &lt;30 weeks and/or a birth weight &lt;1000 g between October 1, 1998 and January 1, 2002 were included. Risk factors included in the study were familial hearing loss, in utero infections, craniofacial anomalies, birth weight &lt;1500g, hyperbilirubinemia, ototoxic medications, cerebral complications, severe birth asphyxia, assisted ventilation ≥5 days and syndromes. Results: A nationwide cohort of 2186 newborns were included. Mean gestational age was 28.5 weeks (SD 1.6) and mean birth weight was 1039 g (SD 256). Prevalence of uni- or bilateral hearing loss was 3.2% (71/2186; 95% CI 2.6-4.1). Multivariate analysis revealed that the only independent risk factors for hearing loss were severe birth asphyxia (OR 1.7; 95% CI 1.0-2.7) and assisted ventilation ≥5 days (OR 3.6; 95% CI 2.1-6.0). Conclusion: The prevalence of hearing loss in a representative NICU population was 3.2%. Independent risk factors for hearing loss were severe birth asphyxia and assisted ventilation ≥5 days.</p

Hearing loss by week of gestation and birth weight in very preterm neonates

OBJECTIVE: To gain insight into health and related costs associated with very preterm births, one needs accurate information about the prevalence of the disabling conditions, including neonatal hearing loss (NHL).STUDY DESIGN: We assessed the prevalence of NHL by week of gestation and categories of birth weight in very preterm neonates. Results of the 2-stage Automated Auditory Brainstem Response nationwide Newborn Hearing Screening Program in Dutch Neonatal Intensive Care Units and diagnostic examinations were centrally registered between October 1998 and December 2012 and included in this study. NHL was defined as impaired when the neonate conventional Auditory Brainstem Response level exceeded 35 dB near Hearing Level at diagnostic examination. Birth weight was stratified into &lt;750 g, 750-999 g, 1000-1249 g, 1250-1499 g, and ≥ 1500 g, and by small for gestational age (SGA; &lt;10th percentile) vs appropriate for gestational age. Logistic regression analyses and recursive partitioning were performed.RESULTS: In total, 18,564 very preterm neonates were eligible. The prevalence of NHL consistently increased with decreasing week of gestation (1.2%-7.5% from 31 to 24 weeks) and decreasing birth weight (1.4%-4.8% from ≥ 1500 g to &lt;750 g, all P &lt; .002). Most vulnerable to NHL were girls &lt;28 weeks, boys &lt;30 weeks, and SGA neonates. The SGA effect started at 27 weeks.CONCLUSIONS: Gestational age and birth weight quantify the risk of NHL. This information can be used at the individual level for parent counseling and at the population level for medical decision making.</p

Evaluation of Treatment Thresholds for Unconjugated Hyperbilirubinemia in Preterm Infants:Effects on Serum Bilirubin and on Hearing Loss?

Background: Severe unconjugated hyperbilirubinemia may cause deafness. In the Netherlands, 25% lower total serum bilirubin (TSB) treatment thresholds were recently implemented for preterm infants.Objective: To determine the rate of hearing loss in jaundiced preterms treated at high or at low TSB thresholds.Design/Methods: In this retrospective study conducted at two neonatal intensive care units in the Netherlands, we included preterms (gestational age 35 dB).Results: There were 479 patients in the high and 144 in the low threshold group. Both groups had similar gestational ages (29.5 weeks) and birth weights (1300 g). Mean and mean peak TSB levels were significantly lower after the implementation of the novel thresholds: 152 +/- 43 mu mol/L and 212 +/- 52 mu mol/L versus 131 +/- 37 mu mol/L and 188 +/- 46 mu mol/L for the high versus low thresholds, respectively (PConclusions: Implementation of lower treatment thresholds resulted in reduced mean and peak TSB levels. The incidence of hearing impairment in preterms with a gestational age</p

Sneutrino Mixing Phenomena

In any model with nonzero Majorana neutrino masses, the sneutrino and antisneutrino of the supersymmetric extended theory mix. We outline the conditions under which sneutrino-antisneutrino mixing is experimentally observable. The mass-splitting of the sneutrino mass eigenstates and sneutrino oscillation phenomena are considered.Comment: 12 pages, revtex + axodraw, 1 figure included. Minor change