Etramp5 as a useful serological marker in children to assess the immediate effects of mass drug campaigns for malaria.

INTRODUCTION: Serological methods provide useful metrics to estimate age-specific period prevalence in settings of low malaria transmission; however, evidence on the use of seropositivity as an endpoint remains scarce in studies to evaluate combinations of malaria control measures, especially in children. This study aims to evaluate the immediate effects of a targeted mass drug administration campaign (tMDA) in Haiti by using serological markers. METHODS: The tMDA was implemented in September-October 2018 using sulfadoxine-pyrimethamine and single low-dose primaquine. A natural quasi-experimental study was designed, using a pretest and posttest in a cohort of 754 randomly selected school children, among which 23% reported having received tMDA. Five antigens were selected as outcomes (MSP1-19, AMA-1, Etramp5 antigen 1, HSP40, and GLURP-R0). Posttest was conducted 2-6 weeks after the intervention. RESULTS: At baseline, there was no statistical difference in seroprevalence between the groups of children that were or were not exposed during the posttest. A lower seroprevalence was observed for markers informative of recent exposure (Etramp5 antigen 1, HSP40, and GLURP-R0). Exposure to tMDA was significantly associated with a 50% reduction in the odds of seropositivity for Etramp5 antigen 1 and a 21% reduction in the odds of seropositivity for MSP119. CONCLUSION: Serological markers can be used to evaluate the effects of interventions against malaria on the risk of infection in settings of low transmission. Antibody responses against Etramp5 antigen 1 in Haitian children were reduced in the 2-6 weeks following a tMDA campaign, confirming its usefulness as a short-term marker in child populations.

Clinical experience with non-invasive prenatal screening for single-gene disorders.

OBJECTIVE: To assess the performance of a non-invasive prenatal screening test (NIPT) for a panel of dominant single-gene disorders (SGD) with a combined population incidence of 1 in 600. METHODS: Cell-free fetal DNA isolated from maternal plasma samples accessioned from 14 April 2017 to 27 November 2019 was analyzed by next-generation sequencing, targeting 30 genes, to look for pathogenic or likely pathogenic variants implicated in 25 dominant conditions. The conditions included Noonan spectrum disorders, skeletal disorders, craniosynostosis syndromes, Cornelia de Lange syndrome, Alagille syndrome, tuberous sclerosis, epileptic encephalopathy, SYNGAP1-related intellectual disability, CHARGE syndrome, Sotos syndrome and Rett syndrome. NIPT-SGD was made available as a clinical service to women with a singleton pregnancy at ≥ 9 weeks' gestation, with testing on maternal and paternal genomic DNA to assist in interpretation. A minimum of 4.5% fetal fraction was required for test interpretation. Variants identified in the mother were deemed inconclusive with respect to fetal carrier status. Confirmatory prenatal or postnatal diagnostic testing was recommended for all screen-positive patients and follow-up information was requested. The screen-positive rates with respect to the clinical indication for testing were evaluated. RESULTS: A NIPT-SGD result was available for 2208 women, of which 125 (5.7%) were positive. Elevated test-positive rates were observed for referrals with a family history of a disorder on the panel (20/132 (15.2%)) or a primary indication of fetal long-bone abnormality (60/178 (33.7%)), fetal craniofacial abnormality (6/21 (28.6%)), fetal lymphatic abnormality (20/150 (13.3%)) or major fetal cardiac defect (4/31 (12.9%)). For paternal age ≥ 40 years as a sole risk factor, the test-positive rate was 2/912 (0.2%). Of the 125 positive cases, follow-up information was available for 67 (53.6%), with none classified as false-positive. No false-negative cases were identified. CONCLUSIONS: NIPT can assist in the early detection of a set of SGD, particularly when either abnormal ultrasound findings or a family history is present. Additional clinical studies are needed to evaluate the optimal design of the gene panel, define target populations and assess patient acceptability. NIPT-SGD offers a safe and early prenatal screening option. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ruling out nosocomial transmission of Cryptosporidium in a renal transplantation unit: case report.

BACKGROUND: Cryptosporidium spp. is a ubiquitous parasite affecting humans as well as domestic and wild vertebrates, causing diarrhea in both immunocompetent and immunocompromised hosts worldwide. Its transmission occurs primarily by the fecal-oral route. In humans, C. parvum and C. hominis are the most prevalent species, whereas immunocompetent and immunocompromised individuals can also be infected by other zoonotic species. Renal transplant patients are prone to develop cryptosporidiosis, which can induce severe and life-threatening diarrhea. CASE PRESENTATION: We report here a series of nearly concomitant cases of acute symptomatic cryptosporidiosis in three renal transplant patients attending the Strasbourg University Hospital Nephrology Unit. The clinical presentation was persistent diarrhea and acute renal failure. The diagnosis was confirmed by microscopic stool examination using a modified Ziehl-Neelsen staining method and species identification by molecular tools. All patients were treated with nitazoxanide and recovered from diarrhea after 14 days of therapy. CONCLUSION: Genotypic species identification was not consistent with an epidemic context, thus underlining the need for genotyping to monitor at risk patients.

Impact of transesophageal electrophysiologic study to elucidate the mechanism of arrhythmia on children with supraventricular tachycardia and no preexcitation.

An electrophysiologic study (EPS) of children and teenagers with paroxysmal supraventricular tachycardia (SVT) and normal electrocardiography (ECG) in sinus rhythm was evaluated. Generally, EPS is performed only before paroxysmal SVT ablation in these patients. In this study, 140 patients (mean age, 15 ± 3 years) with normal ECG in sinus rhythm were studied for SVT by a transesophageal route in baseline state and after isoproterenol. Idiopathic left or right ventricular tachycardia was diagnosed in four patients (3 %). Anterograde conduction over an atrioventricular (AV) left lateral (n = 10) or septal (n = 9) accessory pathway (AP) was noted in 19 patients (13.5 %) at atrial pacing. Orthodromic AV reentrant tachycardia (AVRT) was induced in these children. Five of the patients had a high rate conducted over AP (>240 bpm in baseline state or >290 bpm after isoproterenol). Two of the patients (a 10-year-old girl with well-tolerated SVT and a 17-year-old with syncope-related SVT) had the criteria for a malignant form with the induction of atrial fibrillation conducted over AP at a rate exceeding 290 bpm in baseline state. Of the 140 patients, 74 (53 %) had typical AV node reentrant tachycardia (AVNRT), nine had atypical AVNRT (6 %), 1 had atrial tachycardia (0.7 %), and 33 (23.5 %) had AVRT related to a concealed AP with only retrograde conduction. Electrophysiologic study is recommended for children with paroxysmal SVT and normal ECG in sinus rhythm. The data are helpful for guiding the treatment. Ventricular tachycardia or atrial tachycardia can be misdiagnosed. Masked preexcitation syndrome with anterograde conduction through AP was present in 13.5 % of the patients, and 1.4 % had a malignant preexcitation syndrome.

Photodissociation pathways and lifetimes of protonated peptides and their dimers.

Photodissociation lifetimes and fragment channels of gas-phase, protonated YA(n) (n = 1,2) peptides and their dimers were measured with 266 nm photons. The protonated monomers were found to have a fast dissociation channel with an exponential lifetime of ~200 ns while the protonated dimers show an additional slow dissociation component with a lifetime of ~2 µs. Laser power dependence measurements enabled us to ascribe the fast channel in the monomer and the slow channel in the dimer to a one-photon process, whereas the fast dimer channel is from a two-photon process. The slow (1 photon) dissociation channel in the dimer was found to result in cleavage of the H-bonds after energy transfer through these H-bonds. In general, the dissociation of these protonated peptides is non-prompt and the decay time was found to increase with the size of the peptides. Quantum RRKM calculations of the microcanonical rate constants also confirmed a statistical nature of the photodissociation processes in the dipeptide monomers and dimers. The classical RRKM expression gives a rate constant as an analytical function of the number of active vibrational modes in the system, estimated separately on the basis of the equipartition theorem. It demonstrates encouraging results in predicting fragmentation lifetimes of protonated peptides. Finally, we present the first experimental evidence for a photo-induced conversion of tyrosine-containing peptides into monocyclic aromatic hydrocarbon along with a formamide molecule both found in space.

Sub-microsecond photodissociation pathways of gas phase adenosine 5'-monophosphate nucleotide ions.

The sub-microsecond dissociation pathways for the protonated and deprotonated forms of adenosine 5'-monophosphate were probed in the gas phase using a linear time of flight spectrometer. The studies show two dissociation pathways for the AMP ions indicating dominant ergodic pathways in the photodissociation of these species. The photofragmentation was determined to be a single photon process for the AMP ions. Photodetachment of the AMP anion excited at 266 nm was not observed, leaving dissociation as the prominent pathway for relaxation of the excess energy in the biomolecule. The photofragments were analysed at the electrostatic ion storage ring (ELISA) and found to be similar to collision induced fragments in the case of anions but different in the case of cations.

Ion trajectory simulations in a high-pressure cylindrical ion trap.

We present the simulation of a cylindrical ion trap (CIT) at high pressure (5-25 Torr range). SIMION 7.0 software was used for the simulations. The effect of pressure, RF frequency and trap dimensions has been investigated. The shape of stability diagrams at non-zero pressure is drastically different from the one observed in vacuum. Preliminary experimental results are shown, using a r = z = 3 mm-long CIT at 12 Torr for trapping peptide and protein ions.

Multiple reaction monitoring cubed for protein quantification at the low nanogram/milliliter level in nondepleted human serum.

Mass spectrometry-based strategies for the quantification of low-abundance putative protein biomarkers in human blood currently require extensive sample fractionation steps which hamper their implementation in a routine and robust way across clinical laboratories. We demonstrate that a technique using MS(3) reconstructed chromatograms on a signature of secondary ions issued from a trapped primary product ion, termed multiple reaction monitoring cubed (MRM(3)), enables targeting protein biomarkers in the low nanogram/milliliter range in nondepleted human serum. The simple two-step workflow is based on a trypsin proteolysis of whole serum (100 microL) followed by enrichment of targeted proteotypic peptides on a solid phase extraction column using mixed-cation exchange resin. MRM(3)'s fidelity of peak detection extends the dynamic range and limit of quantitation (LOQ) of protein biomarkers to the low nanogram/milliliter range, corresponding to a concentration that is 10(6)-fold lower than the concentration of the most abundant proteins in serum. The power of the MRM(3) method is illustrated by the assay of prostate specific antigen in nondepleted human sera of patients. The results correlate well with the established method for determining PSA levels in serum, i.e., enzyme-linked immunosorbent assay (ELISA) tests.

Development of isohomoeoallelic lines within the wheat cv. Courtot for high molecular weight glutenin subunits: transfer of the Glu-D1 locus to chromosome 1A.

Wheat quality depends on protein composition and grain protein content. High molecular weight glutenin subunits (HMW-GS) play an important role in determining the viscoelastic properties of gluten. In an attempt to improve the bread-making quality of hexaploid wheat by elaborating novel HMW-GS combinations, a fragment of wheat chromosome 1D containing the Glu-D1 locus encoding the Dx2+Dy12 subunits was translocated to the long arm of chromosome 1A using the ph1b mutation. The partially isohomoeoallelic line selected was characterized using cytogenetical and molecular approaches to assess the amount of chromatin introgressed in the translocated 1A chromosome. Triple-target genomic in situ hybridization indicated that the translocated 1A chromosome had a terminal 1D segment representing 25% of the length of the recombinant long arm. The translocation was also identified on the long arm using molecular markers, and its length was estimated with a minimum of 91 cM. Proteome analysis was performed on total endosperm proteins. Out of the 152 major spots detected, 9 spots were up-regulated and 4 spots were down-regulated. Most of these proteins were identified as alpha-, beta-, gamma-gliadins assigned to the chromosomes of homoeologous groups 1 and 6. Quantitative variations in the HMW-GS were only observed in subunit Dy12 in response to duplication of the Glu-D1 locus.

Surgical treatment of congenital pseudarthrosis of the forearm: Review and quantitative analysis of individual patient data.

There is little scientific evidence on the best surgical treatment for congenital pseudarthrosis of the forearm due to the rarity of this condition (less than 100 cases described in the literature) and the lack of comparative studies. Our aim was to provide evidence in favor of a certain surgical technique. A comprehensive review of the literature was performed using case series and case reports. The statistical analysis was based on individual patient data to mimic a case-control study. A multiple logistic regression was used to assess the effect of each independent variable (neurofibromatosis status, location of the pseudarthrosis, age at first surgery and type of treatment) on bone union at last follow-up (yes/no). The database searches yielded 1112 articles; 55 articles were selected, reporting on 94 cases. Seventy patients had healed completely at the last follow-up (74%). Neither the age at surgery nor the location of the pseudarthrosis was related to union (P>0.7). The patients' neurofibromatosis type 1 status was weakly related to healing (P=0.06). Vascularized fibula transfer had a higher rate of healing (100%) than did non-vascularized bone graft (70%) (P=$0.002). LEVEL OF EVIDENCE: 4 (case-control study of data from case series and case reports).