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Background While rotavirus causes severe diarrheal disease in children aged Methods In the Vaccine Impact on Diarrhea in Africa study (2015–2018), we analyzed stool from children aged 0–59 months with moderate-to-severe diarrhea (MSD) and without diarrhea (controls) in Kenya, Mali, and The Gambia using quantitative polymerase chain reaction. We derived the attributable fraction (AFe) based on the association between MSD and the pathogen, accounting for other pathogens, site, and age. A pathogen was attributable if the AFe was ≥0.5. The severity of attributable MSD was defined by a modified Vesikari score (mVS). Monthly cases were plotted against temperature and rainfall to assess seasonality. Results Among 4840 MSD cases, proportions attributed to rotavirus, adenovirus 40/41, astrovirus, and sapovirus were 12.6%, 2.7%, 2.9%, and 1.9%, respectively. Attributable rotavirus, adenovirus 40/41, and astrovirus MSD cases occurred at all sites, with mVS of 11, 10, and 7, respectively. MSD cases attributable to sapovirus occurred in Kenya, with mVS of 9. Astrovirus and adenovirus 40/41 peaked during the rainy season in The Gambia, while rotavirus peaked during the dry season in Mali and The Gambia. Conclusions In sub-Saharan Africa, rotavirus was the most common cause of MSD; adenovirus 40/41, astrovirus, and sapovirus contributed to a lesser extent among children aged

Background Despite antibiotic prescription being recommended for dysentery and suspected cholera only, diarrhea still triggers unwarranted antibiotic prescription. We evaluated antibiotic-prescribing practices and their predictors among children aged 2–59 months in the Vaccine Impact on Diarrhea in Africa (VIDA) Study performed in The Gambia, Mali, and Kenya. Methods VIDA was a prospective case-control study (May 2015–July 2018) among children presenting for care with moderate-to-severe diarrhea (MSD). We defined inappropriate antibiotic use as prescription or use of antibiotics when not indicated by World Health Organization (WHO) guidelines. We used logistic regression to assess factors associated with antibiotic prescription for MSD cases who had no indication for an antibiotic, at each site. Results VIDA enrolled 4840 cases. Among 1757 (36.3%) who had no apparent indication for antibiotic treatment, 1358 (77.3%) were prescribed antibiotics. In The Gambia, children who presented with a cough (adjusted odds ratio [aOR]: 2.05; 95% confidence interval [95% CI]: 1.21–3.48) were more likely to be prescribed an antibiotic. In Mali, those who presented with dry mouth (aOR: 3.16; 95% CI: 1.02–9.73) were more likely to be prescribed antibiotics. In Kenya, those who presented with a cough (aOR: 2.18; 95% CI: 1.01–4.70), decreased skin turgor (aOR: 2.06; 95% CI: 1.02–4.16), and were very thirsty (aOR: 4.15; 95% CI: 1.78–9.68) were more likely to be prescribed antibiotics. Conclusions Antibiotic prescription was associated with signs and symptoms inconsistent with WHO guidelines, suggesting the need for antibiotic stewardship and clinician awareness of diarrhea case-management recommendations in these settings.

Background Diarrheal disease is heterogeneous, including watery diarrhea (WD) and dysentery, some cases of which become persistent diarrhea (PD). Changes in risk over time necessitate updated knowledge of these syndromes in sub-Saharan Africa. Methods The Vaccine Impact on Diarrhea in Africa (VIDA) study was an age-stratified, case-control study of moderate-to-severe diarrhea among children Results Among 4606 children with moderate-to-severe diarrhea, 3895 (84.6%) had WD and 711 (15.4%) had dysentery. PD was more frequent among infants (11.3%) than in children 12–23 months (9.9%) or 24–59 months (7.3%), P = .001 and higher in Kenya (15.5%) than in The Gambia (9.3%) or Mali (4.3%), P < .001; the frequencies were similar among children with WD (9.7%) and those with dysentery (9.4%). Compared to children not treated with antibiotics, those who received antibiotics had a lower frequency of PD overall (7.4% vs 10.1%, P = .01), and particularly among those with WD (6.3% vs 10.0%; P = .01) but not among children with dysentery (8.5% vs 11.0%; P = .27). For those with watery PD, Cryptosporidium and norovirus had the highest AFs among infants (0.16 and 0.12, respectively), while Shigella had the highest AF (0.25) in older children. The odds of PD decreased significantly over time in Mali and Kenya while increasing significantly in The Gambia. Conclusions The burden of PD endures in sub-Saharan Africa, with nearly 10% of episodes of WD and dysentery becoming persistent.

Background To address knowledge gaps regarding diarrheagenic Escherichia coli (DEC) in Africa, we assessed the clinical and epidemiological features of enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), and Shiga toxin–producing E. coli (STEC) positive children with moderate-to-severe diarrhea (MSD) in Mali, The Gambia, and Kenya. Methods Between May 2015 and July 2018, children aged 0–59 months with medically attended MSD and matched controls without diarrhea were enrolled. Stools were tested conventionally using culture and multiplex polymerase chain reaction (PCR), and by quantitative PCR (qPCR). We assessed DEC detection by site, age, clinical characteristics, and enteric coinfection. Results Among 4840 children with MSD and 6213 matched controls enrolled, 4836 cases and 1 control per case were tested using qPCR. Of the DEC detected with TAC, 61.1% were EAEC, 25.3% atypical EPEC (aEPEC), 22.4% typical EPEC (tEPEC), and 7.2% STEC. Detection was higher in controls than in MSD cases for EAEC (63.9% vs 58.3%, P < .01), aEPEC (27.3% vs 23.3%, P < .01), and STEC (9.3% vs 5.1%, P < .01). EAEC and tEPEC were more frequent in children aged Conclusions No significant association was detected between EAEC, tEPEC, aEPEC, or STEC and MSD using either conventional assay or TAC. Genomic analysis may provide a better definition of the virulence factors associated with diarrheal disease.

Background We evaluated the burden of Shigella spp from children aged 0–59 months with medically attended moderate-to-severe diarrhea and matched controls at sites in Mali, The Gambia, and Kenya participating in the Vaccine Impact on Diarrhea in Africa (VIDA) study from 2015 to 2018. Methods Shigella spp were identified using coprocultures and serotyping in addition to quantitative polymerase chain reaction (qPCR). Episode-specific attributable fractions (AFe) for Shigella were calculated using Shigella DNA quantity; cases with AFe ≥0.5 were considered to have shigellosis. Results The prevalence of Shigella was determined to be 359 of 4840 (7.4%) cases and 83 of 6213 (1.3%) controls by culture, and 1641 of 4836 (33.9%) cases and 1084 of 4846 (22.4%) controls by qPCR (cycle threshold Conclusions A high prevalence of shigellosis continues in sub-Saharan Africa. Strains are highly resistant to commonly used antibiotics while remaining susceptible to ciprofloxacin, ceftriaxone, and azithromycin.

In the MORDOR I trial, children under 5 years of age were randomized to receive biannual (every 6 months) azithromycin for 2 years in Niger, Malawi, and Tanzania. In 30 Nigerien communities, children aged 7–11 years, who were not enrolled in the MORDOR I trial to receive biannual azithromycin, were assessed for carriage of seven respiratory pathogens. We aimed to see whether there were effects on the carriage of these seven respiratory pathogens among 3,187 children aged 7–11 years living in the 30 communities via nasopharyngeal swabs collected at baseline (N = 1,066), as well as at year 1 (N = 1,019) and year 2 (N = 1,102)—each about 6 months after azithromycin or placebo treatment of children under age five. Most children were positive for Haemophilus influenzae (baseline: 83.8%; interquartile range [IQR]: 78.7–90.4) and Streptococcus pneumoniae (baseline: 82.9%; IQR: 74.2–86.8) at all time points regardless of treatment group. There were no differences in prevalence nor quantity of H. influenzae (prevalence ratio: 0.95; 95% CI: 0.90, 1.02), S. pneumoniae (prevalence ratio: 1.01; 95% CI: 0.96, 1.07), or any of the other respiratory pathogens in the treatment versus control groups at any time point. S. pneumoniae serotype 6AB (7.7%) and Neisseria meningitidis serotype W135 (24.9%) were the most prevalent serotypes detected among all positive S. pneumoniae and N. meningitidis samples, respectively. Biannual azithromycin did not reduce carriage of respiratory pathogens 6 months after the most recent round of biannual azithromycin among older nontreated children (aged 7–11 years) living in treatment communities.

We present a combined experimental and theoretical study of the nature of the proposed metal-metal bonding in the tetranuclear cluster Ni4(NPtBu3)4, which features four nickel(I) centers engaged in strong ferromagnetic coupling. High-resolution single-crystal synchrotron X-ray diffraction data collected at 25 K provide an accurate geometrical structure and a multipole model electron density description. Topological analysis of the electron density in the Ni4N4 core using the quantum theory of atoms in molecules clearly identifies the bonding as an eight-membered ring of type [Ni-N-]4 without direct Ni-Ni bonding, and this result is generally corroborated by an analysis of the energy density distribution. In contrast, the calculated bond delocalization index of ∼0.6 between neighboring Ni atoms is larger than what has been found for other bridged metal-metal bonds and implies direct Ni-Ni bonding. Similar support for the presence of direct Ni-Ni bonding is found in the interacting quantum atom approach, an energy decomposition scheme, which suggests the presence of stabilizing Ni-Ni bonding interactions with an exchange-correlation energy contribution approximately 50% of that of the Ni-N interactions. Altogether, while the direct interactions between neighboring Ni centers are too weak and sterically constrained to bear the signature of a topological bond critical point, other continuous measures clearly indicate significant Ni-Ni bonding. These metal-metal bonding interactions likely mediate direct ferromagnetic exchange, giving rise to the high-spin ground state of the molecule.

To describe the epidemiology and risk factors for Clostridioides difficile (C. difficile) colonization among young children in eight low-resource settings.We tested 41 354 monthly non-diarrhoeal and diarrhoeal stools for C. difficile toxin genes (TcdA and TcdB) using quantitative PCR (qPCR) in 1715 children from birth to age two years in a multisite birth cohort study. We estimated the prevalence, cumulative incidence, and seasonality of C. difficile colonization and investigated the associations of C. difficile detection with risk factors of infection, markers of enteropathy, and growth.The prevalence of C. difficile detection was lower in diarrhoeal (2.2%; n = 151/6731) compared to non-diarrhoeal stools (6.1%; n = 2106/34 623). By 24 months of age, the cumulative incidence of C. difficile varied widely by site, with 17.9% (n = 44; Pakistan) to 76.3% (n = 148; Peru) of children having at least one positive stool. Only Bangladesh and Pakistan had seasonal differences in C. difficile detection. Female sex (adjusted risk ratio (aRR): 1.18; 95% CI: 1.02-1.35), cephalosporin use in the past 15 days (aRR: 1.73; 95% CI: 1.39-2.16), and treated water (aRR: 1.24; 95% CI: 1.02-1.50) were risk factors for C. difficile positivity. The presence of C. difficile was significantly associated with elevated faecal myeloperoxidase, neopterin, and α-1-antitrypsin, but no associations were found between C. difficile and child growth at 24 months of age.C. difficile colonization among children ages 0-2 years was variable across low-resource settings. Significant elevation of intestinal inflammation and barrier disruption markers associated with C. difficile detection suggests a subclinical impact of colonization.

Background The magnitude of pediatric enteric pathogen exposures in low-income settings necessitates substantive water and sanitation interventions, including animal feces management. We assessed associations between pediatric enteric pathogen detection and survey-based water, sanitation, and animal characteristics within the Vaccine Impact on Diarrhea in Africa case-control study. Methods In The Gambia, Kenya, and Mali, we assessed enteric pathogens in stool of children aged Results Bacterial (cases, 93%; controls, 72%), viral (63%, 56%), and protozoal (50%, 38%) pathogens were commonly detected (cycle threshold Conclusions Findings underscore the importance of enteric pathogen exposure risks from animals alongside more broadly recognized water and sanitation risk factors in children.

Background Diarrheal diseases are a leading cause of death for children aged Methods We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) study to build predictive models for diarrhea of Shigella etiology in children aged ≤59 months presenting with moderate to severe diarrhea in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using cross-validation. We used the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study to externally validate our GEMS-derived CPR. Results Of the 5011 cases analyzed, 1332 (27%) had diarrhea of Shigella etiology. Our CPR had high predictive ability (area under the receiver operating characteristic curve = 0.80 [95% confidence interval, .79–.81]) using the top 2 predictive variables, age and caregiver-reported bloody diarrhea. We show that by using our CPR to triage who receives diagnostic testing, 3 times more Shigella diarrhea cases would have been identified compared to current symptom-based guidelines, with only 27% of cases receiving a POC diagnostic test. Conclusions We demonstrate how a CPR can be used to guide use of a POC diagnostic test for diarrhea management. Using our CPR, available diagnostic capacity can be optimized to improve appropriate antibiotic use.

BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation. publishedVersion

We analyzed samples obtained at baseline and 24 months in a mass azithromycin administration trial in Niger using quantitative polymerase chain reaction. In villages randomized to azithromycin, Shigella was the only pathogen reduced at 24 months (prevalence ratio, 0.36 [95% confidence interval: .17–.79]; difference in log quantity, −.42 [−.75 to −.10]).

BackgroundDiarrheal diseases are a leading cause of death for children under-5.Identification of etiology helps guide pathogen-specific therapy, but availability of diagnostic testing is often limited in low resource settings. Our goal is to develop a clinical prediction rule (CPR) to guide clinicians in identifying when to use a point-of-care diagnostic forShigellain children presenting with acute diarrhea.MethodsWe used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) study to build predictive models for diarrhea ofShigellaetiology in children ≤59 months presenting with moderate-to-severe diarrhea in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using cross-validation. We used the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study to externally validate our GEMS-derived CPR.ResultsOf the 5011 cases analyzed, 1332 (27%) had diarrhea ofShigellaetiology. Our CPR had high predictive ability (AUC=0.80 (95% CI: 0.79, 0.81) using the top two predictive variables, age and caregiver reported bloody diarrhea. We show that by using our CPR to triage who receives diagnostic testing, 3 times moreShigelladiarrhea cases would have been identified compared to current symptom-based guidelines, with only 27% of cases receiving a point-of-care diagnostic test.ConclusionsWe demonstrate how a clinical prediction rule can be used to guide use of a point-of-care diagnostic test for diarrhea management. Using our CPR, available diagnostic capacity can be optimized to improve appropriate antibiotic use.Key pointsUsing an externally validated clinical prediction tool to triage who receives diagnostic testing, 3 times moreShigelladiarrhea cases would have been identified compared to current symptom-based guidelines, with only 27% of cases receiving a point-of-care diagnostic test.

The charge density distribution in a novel cocrystal (1) complex of 1,3-dimethylxanthine (theophylline) and propanedioic acid (malonic acid) has been determined. The molecules crystallize in the triclinic, centrosymmetric space group P1̅, with four independent molecules (Z = 4) in the asymmetric unit (two molecules each of theophylline and malonic acid). Theophylline has a notably high hygroscopic nature, and numerous cocrystals have shown a significant improvement in stability to humidity. A charge density study of the novel polymorph has identified interesting theoretical results correlating the stability enhancement of theophylline via cocrystallization. Topological analysis of the electron density highlighted key differences (up to 17.8) in Laplacian (∇2ρ) between the experimental (EXP) and single-point (SP) models, mainly around intermolecular-bonded carbonyls. Further investigation via molecular electrostatic potential maps reaffirmed that the charge redistribution enhanced intramolecular hydrogen bonding, predominantly for N(2′) and N(2) (61.2 and 61.8 kJ mol–1, respectively). An overall weaker lattice energy of the triclinic form (−126.1 kJ mol–1) compared to that of the monoclinic form (−133.8 kJ mol–1) suggests a lower energy threshold to overcome to initiate dissociation. Future work via physical testing of the novel cocrystal in both dissolution and solubility will further solidify the correlation between theoretical and experimental results.

We report the accelerated molecular dynamics (aMD) simulation of amyloid-β (Aβ) peptides of four different lengths (16, 28, 40, and 42 residues) and their complexes when bound to Cu(II), Fe(II), or Zn(II). 600 ns equilibrated trajectory data were analyzed for each structure from three independent 200 ns aMD simulations, generating 16 aMD trajectories. We show that the presence of a metal ion leads to reduced size and decreased mobility relative to the free peptide due to the anchoring effect of the ions. The reduced mobility was shown largely to be due to the restricted movement in N-terminal residues, most notably Asp1 and His6 that are involved in the metal-ion coordination in all cases. Significant disruption of the secondary structure and patterns of salt bridge interactions arise on the coordination of metal ions. In this regard, similarities were noted between results for Zn(II) and Fe(II), whereas results for Cu(II) are more comparable to that of the free peptides. Reweighting of free energy surfaces was carried out from aMD data to identify the properties and descriptions of local minima structures.

Summary Background The odds ratio (OR) comparing pathogen presence in diarrhoeal cases versus asymptomatic controls is a measure for diarrhoeal disease cause that has been integrated into burden of disease estimates across diverse populations. This study aimed to estimate the OR describing the association between pathogen detection in stool and diarrhoea for 15 common enteropathogens by age group and child mortality setting. Methods We did a systematic review to identify case-control and cohort studies published from Jan 1, 1990, to July 9, 2019, which examined at least one enteropathogen of interest and the outcome diarrhoea. The analytical dataset included data extracted from published articles and supplemented with data from the Global Enteric Multicenter Study and the Malnutrition and Enteric Disease study. Random effects meta-analysis models were fit for each enteropathogen, stratified by age group and child mortality level, and adjusted for pathogen detection method and study design to produce summary ORs describing the association between pathogen detection in stool and diarrhoea. Findings 1964 records were screened and 130 studies (over 88 079 cases or diarrhoea samples and 135 755 controls or non-diarrhoea samples) were available for analysis. Heterogeneity (I2) in unadjusted models was substantial, ranging from 27·6% to 86·6% across pathogens. In stratified and adjusted models, summary ORs varied by age group and setting, ranging from 0·4 (95% CI 0·2–0·6) for Giardia lamblia to 54·1 (95% CI 7·4–393·5) for Vibrio cholerae. Interpretation Incorporating effect estimates from diverse data sources into diarrhoeal disease cause and burden of disease models is needed to produce more representative estimates. Funding WHO, Bill & Melinda Gates Foundation, and National Institutes of Health.

We report the formation of dinuclear complexes from, and photochemical oxidation of, (CH3)3-Pt(IV)(N^N) (N^N = 1,2-diimine derivatives) complexes of thiophenolate ligands to the analogous sulfinates (CH3)3Pt(N^N)(SO2Ph) and structural, spectroscopic, and theoretical studies of the latter revealing tunable photophysics depending upon the 1,2-diimine ligands. Electron-rich thiolate and conjugated 1,2-diimines encourage formation of thiolate-bridged dinuclear complexes; smaller 1,2-diimines or electron-poor thiolates favor mononuclear complexes. Photooxidation of the thiolate ligand yields hitherto unreported Pt(IV)-SO2R complexes, promoted by electron-deficient thiolates such as 4-nitrothiophenol, which exclusively forms the sulfinate complex. Such complexes exhibit expected absorptions due to π-π* ligand transitions of the 1,2-diimines mixed with spin-allowed singlet MLCT (d-π*) at relatively high energy (270–290 nm), as well as unexpected broad, lower energy absorptions between 360 and 490 nm. DFT data indicate that these low energy absorption bands result from excitation of Pt–S and Pt–C σ-bonding electrons to π* orbitals on sulfinate and 1,2-diimine, the latter of which gives rise to emission in the visible range.

BackgroundDiarrheal disease remains a leading cause of childhood illness and mortality and Shigella is a major etiological contributor for which a vaccine may soon be available. This study aimed to model the spatiotemporal variation in pediatric Shigella infection and map its predicted prevalence across low- and middle-income countries (LMICs).MethodsIndependent participant data on Shigella positivity in stool samples collected from children aged ≤59 months were sourced from multiple LMIC-based studies. Covariates included household- and subject-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted, and prevalence predictions obtained by syndrome and age stratum.Findings20 studies from 23 countries contributed 66,563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Shigella probability exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhea cases at 33°C temperatures, above which it decreased. Improved sanitation and open defecation decreased Shigella odds by 19% and 18% respectively compared to unimproved sanitation.InterpretationThe distribution of Shigella is more sensitive to climatological factors like temperature than previously recognized. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, though hotspots also occur in South and Central America, the Ganges–Brahmaputra Delta, and New Guinea. These findings can inform prioritization of populations for future vaccine trials and campaigns.FundingNASA 16-GEO16-0047; NIH-NIAID 1R03AI151564-01; BMGF OPP1066146.

We report conventional and accelerated molecular dynamics simulations of α-Synuclein, designed to assess performance of using different starting conformation, solvation environment and force field combination. Backbone and sidechain chemical shifts, radius of gyration, presence of β-hairpin structures in KTK(E/Q)GV repeats and secondary structure percentages were used to evaluate how variations in forcefield, solvation model and simulation protocol provide results that correlate with experimental findings. We show that with suitable choice of forcefield and solvent, ff03ws and OBC implicit model, respectively, acceptable reproduction of experimental data on size and secondary structure is obtained by both conventional and accelerated MD. In contrast to the implicit solvent model, simulations in explicit TIP4P/2005 solvent do not properly represent size or secondary structure of α-Synuclein. Communicated by Ramaswamy H. Sarma

This study investigated the effect of 2-methylimidazole (2-MIM) addition on the fluorescence of ethyl-7-hydroxy-2-oxo-2H-chromene-3-carboxylate using low-cost density functional theory (DFT) and Time-Dependent DFT calculations on single crystal X-ray geometries of ethyl-7-hydroxy-2-oxo-2H-chromene-3-carboxylate hydrate (1), 2-MIM (2), and the 1 : 1 co-crystal of (1) and (2), (3). At low concentrations (1 : 1–1 : 10) of 2-MIM, the fluorophore shows a decrease in the fluorescence intensity, but at higher concentrations (above 1 : 10) the fluorescence excitation maximum shifted from 354 nm to 405 nm, with a significant emission intensity increase. The changed excitation and emission profile at high concentrations is due to the deprotonation of the coumarin's phenolic group, which was confirmed by the increased shielding of the aromatic protons in the titration 1H NMR spectra. The experimental fluorescence data between the 1 : 1 and 1 : 10 ratios agreed with the theoretical fluorescence data, with a redshift and decreased intensity when comparing (1) and (3). The data indicated that combining the fluorophore with 2-MIM increased levels of vibronic coupling between 2-MIM and the fluorophore decreasing de-excitation efficiency. These increased vibronic changes were due to charge transfer between the fluorophore and 2-MIM in (3). The subtle movement of the proton, H(5) toward N(2′) (0.07 Å) caused a significant decrease in fluorescence due to electron density distribution (EDD) changes. This was identified by comparison of the EDD in the excited (S1) and ground (S0) states plotted as an isosurface of EDD difference. For the higher concentrations, an alternative excitation pathway was explored by modifying the crystal geometry of (3) based on 1H NMR spectroscopy data to resemble excitoplexes. Theses excitoplex geometries reflected the fluorescence profile of the fluorophore with high concentrations of 2-MIM; there were dramatic changes in the theoretical fluorescence pathway, which was 100% vibronic coupling compared to 15.31% in the free fluorophore. At this concentration, the de-excitation pathway causes remodelling of the lactone ring via stretching/breaking the C[double bond, length as m-dash]O bond in the S1 causing increased fluorescence by movement of the transition dipole moment. These results reflect previous studies, but the methods used are less experimentally and computationally expensive. This study is among the first to explain charge transfer fluorescence using crystalline geometries. This study will be of interest to the fields of crystal engineering and fluorescence spectroscopy.

An asymmetric bipy/NHC ligand L has been used to construct Au/Au, Au/Ag and Au/Cu bimetallic complexes through prior coordination of the NHC to Au(I) and subsequent introduction of the second group 11 metal ion at the bipy donor of the hybrid ligand. The complex [Au(κC-L)2]BF4, 1, has been used as the precursor for the formation of [AuAg(κ-CAu,κ2-N,N′Ag-1)2](BF4)2, 2a, [AuCu(κ-CAu,κ2-N,N′Cu-1)2](BF4)2, 2b and [AuAu′(κ-CAu/Au′,κ1-NAu/Au′-1)2](BF4)2, 3.

Background Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. Methods We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold, Molecular methods identified Shigella more commonly than microbiologic culture in younger and stunted children. A simplified clinical score containing dehydration, hospitalization, and diarrhea duration could be used to stratify vaccine trial endpoints by severity based on its ability to predict death.

Background Prolonged enteropathogen shedding after diarrhea complicates the identification of etiology in subsequent episodes and is an important driver of pathogen transmission. A standardized approach has not been applied to estimate the duration of shedding for a wide range of pathogens. Methods We used a multisite birth cohort of children 0–24 months of age from whom diarrheal and monthly nondiarrheal stools were previously tested by quantitative polymerase chain reaction for 29 enteropathogens. We modeled the probability of detection of the etiologic pathogen before and after diarrhea using a log-normal accelerated failure time survival model and estimated the median duration of pathogen carriage as well as differences in subclinical pathogen carriage 60 days after diarrhea onset in comparison to a prediarrhea baseline. Results We analyzed 3247 etiologic episodes of diarrhea for the 9 pathogens with the highest attributable burdens of diarrhea. The median duration of postdiarrheal carriage varied widely by pathogen, from about 1 week for rotavirus (median, 8.1 days [95% confidence interval {CI}, 6.2–9.6]) to >1 month for Cryptosporidium (39.5 days [95% CI, 30.6–49.0]). The largest increases in subclinical pathogen carriage before and after diarrhea were seen for Cryptosporidium (prevalence difference between 30 days prior and 60 days after diarrhea onset, 0.30 [95% CI, .23–.39]) and Shigella (prevalence difference, 0.21 [95% CI, .16–.27]). Conclusions Postdiarrheal shedding was widely variable between pathogens, with strikingly prolonged shedding seen for Cryptosporidium and Shigella. Targeted antimicrobial therapy and vaccination for these pathogens may have a relatively large impact on transmission., In a multisite birth cohort study of children 0–24 months of age and with quantitative polymerase chain reaction detection of diarrheal pathogens, we estimate the duration of postdiarrheal carriage in low-resource settings, with strikingly prolonged shedding seen for Cryptosporidium and Shigella.

In a cohort of infants, we found that lack of the Lewis histo-blood group antigen was associated with increased susceptibility to shigellosis. Broadly inhibiting fucosylation in epithelial cells in vitro decreased invasion by Shigella flexneri. These results support a role for fucosylated glycans in susceptibility to shigellosis.