The specimens at different growth stages are investigated by using X-ray diffraction, electron microscopy, energy dispersive X-ray spectroscopy, soft X-ray emission spectroscopy and infrared spectroscopy. The formation mechanism of Cu2O spherulites is proposed accordingly. Hierarchically, the spherulites are composed of needle-like submicron-rods lying along the radial orientations. The submicron-rods are constructed by piling up of small Cu2O/PVP spheres. The embedded Cu2O nanocrystallites can generate a dipolar field in each along the [100] direction. They deposit at the surface of a negatively charged PVP-containing spherical core, and self-oriented along the radial directions. Therefore, all the Cu2O nanocrystallites would have their positively charged (100) facet facing to the core and their negatively charged (1̄00) facet turning towards to the spherulite surface, leading to a negatively charged surface of spherulites. Unlike randomly oriented nanocrystallites embedded in polymer microspheres, the spherulites would not undergo surface recrystallisation into a single crystal shell due to the restricted potential of local shift and rotation of the nanocrystallites by the Coulomb force from the core. This work provides new perspective towards the formation of spherulites and their structural properties.Cu 2O/PVP spherulites are synthesised using Cu(NO3)2 as precursor, PVP as a reductant/capping-agent and DMF as the solvent. The interaction between dipoles of Cu2O nanocrystals and a negatively charged core plays an important role in their formation.Cu A bulk crystal of metal oxide normally possess no dipolar field even it is constructed alternately by negatively and positively charged atomic layers. It is because the surface roughness by horizontal zig-zag arrangement of atoms can make the surface atomic layers neutral. However, in nanocrystallites, smooth surface terminal atomic layers with either positive or negative charge can form easily, leading to a dipolar field. The formation of biomimetic vaterite spherulites is a good example,7 where all the nanocrystallites were self-oriented into a parallel manner when a strong electric field in the core did not exist, while turned to radial orientations when a strong dipolar field from a double layered structure was developed in the cores.The formation of acicular morphology inside spherulites often associate with ordering or partial ordering of nanocrystallites. One principal argument for the driving force of self-orientation of nanocrystallites in spherulites is probably the dipolar field developed in nanocrystallites.11 corallites,12 and synthetic CaCO3,3,5 ZnO,6,13 Ni3Ge,14 polymer,15 MOF,16etc. Carbonate spherulites are investigated as an important geological research project in the recent years, because these millimetre sized particles may be an evidence of existence of oil-prone alginite.17 Their biotic growth mechanism and microstructures may carry information of the environmental conditions during their formation millions years ago.5 Metal oxide spherulites normally have complicated microstructures with nanocrystallites embedded in a polymer substrate. The organic substrate is a soft matter. It not only prevents further growth of the nanocrystallites, but also allow the local shift and rotation of the nanocrystallites. This property is crucial for the self-orientation of the embedded nanocrystallites in the spherulites.Spherulites have been found in various compositions, including naturally occurring rhyolite,4·5H2O as precursor, polyvinylpyrrolidone (PVP) as a reductant/capping-agent and dimethylformamide (DMF) as the solvent, Cu2O/PVP composite spherulites were detected as an intermediate phase.18 The Cu2O nanocrystallites in these spherulites were further reduced into Cu nanocrystallites, therefore these spherulites were not preserved. Cu2O is a promising semiconductor and photocatalyst in reduction of CO2,19 dye degradation,20 H2 production,21etc. Various morphologies of Cu2O are widely studied, for instance, cube,22 dendrite,23 hollow structure,24 26-facet polyhedron.25 However, the formation mechanism of spherulitic Cu2O has not been investigated in details. A research of Cu2O-containing in depth would not only improve our control power of Cu2O spherulites, but also contribute to our better understanding of general formation mechanisms of other spherulites.In our recent research of the formation of Cu pseudo-icosahedral microcrystals using CuSO2O spherulites and proposed the formation mechanism. The effects of NO3− anions on the reduction of copper and multifunction of PVP as an agglomerating surfactant as well as a weak reducing agent are discussed. We find that, due to alignment of nanocrystallites guided by the negatively charge PVP-rich cores, the whole surface of the spherulites is negatively charged. We anticipate this work can shed lights on the future studies in the field and control of spherulitic morphologies. Hopefully the newly obtained knowledge can be applied in crystal engineering and geology.Herein, we report the growth and characterisation of relatively stable Cu3)2·H2O (Sigma-Aldrich), PVP , DMF , deionised water (DI water) with a resistivity of 18.3 M Ω cm−1. All chemicals were used as received without further purification.The materials used in the present work were Cu(NO3)2·H2O. The solution was stirred continuously for about 15 min when it became a green suspension. The suspension was then transferred into an autoclave vessel and put into an oven at 150 °C. The suspension was kept at this temperature for a certain time for the crystal growth. Several reaction times  were applied to obtain specimens from different growth stages for a study of morphology evolution and microstructural changes. When the reaction was stopped, the sample was filtered and washed three times with DI water to remove excess DMF and PVP. Finally, the obtained solid specimen was dried at 50 °C. All experiments were performed three times to make sure they were repeatable.0.5 g PVP were fully dissolved in 25 ml DMF and preheated to 150 °C before addition of 1.25 mmol Cu for observation. In a parallel experiment, chitosan was used to replace alginate with all other conditions unchanged.Further test to confirm the surface charge of the spherulites was agglomeration experiment. 0.05 g sodium alginate were dissolved in 10 mL DI water. The solution was stirred when 10 mL Cu1α (λ = 1.5418 Å) radiation. The size of capillary is 0.5 mm in inner diameter. The diffracted X-rays were collected using a scintillation position-sensitive linear detector. Samples were scanned for 12 h to get their XRD patterns. SEM images were recorded using JEOL JSM-IT200 and JSM-IT800 microscopes operated from 5 kV to 15 kV. Samples were coated with a thin gold layer for 60 seconds in 10 mA to overcome the charging problem. Energy dispersive X-ray spectroscopy (EDX) was performed on the JEOL JSM-IT800 SEM operating at 15 kV. Soft X-ray emission spectroscopy (SXES) data was collected in SEM IT800 using SXES detector at −70 °C for 1 h each. Specimens for EDX and SXES studies were deposited on silica substrates, instead of carbon tapes, without gold coating to avoid detecting external carbon and gold. Fourier transform infrared spectroscopy (FTIR) data was collected on a Shimadzu IRAffinity-1s FTIR spectrometer. Transmission electron microscopy (TEM) and high resolution TEM (HRTEM) images were obtained using JEOL JEM 2011 and FEI Titan Themis 200 S/TEM (in TEM mode) both operated at 200 kV. EDX elemental mapping on FEI Titan Themis 200 was achieved in STEM mode and also at 200 kV. Samples for TEM/HRTEM observation were dispersed in acetone or ethanol, and deposited onto a TEM specimen grid coated with a holey carbon film.Powder X-ray diffraction (XRD) characterisation was performed on a STOE diffractometer in Debye–Scherrer (capillary) mode in room temperature using Cu K2O. SEM images revealed that the morphologies of all obtained samples were spherical with smooth surfaces as shown in e.g. 10.1 μm after 3 h, 10.3 μm after 6 h, 10.3 μm after 12 h, and 10.5 μm after 96 h. The increase of the particle size is not significant.All the samples with different reaction times from 1.5 to 96 h showed dark brown, a typical colour for Cu2O, which has a cubic structure with the unit cell parameter a = 4.268 Å. In 12 h sample, two extra weak peaks appear and can be indexed to the face-centred cubic structure of Cu with a = 3.615 Å. Cu as a minor phase is believed to be resulted from further reduction of Cu2O by the weak reducing agent PVP. But, this process is very slow.XRD was then applied to examine the crystalline phases in the samples and their crystallinities. As displayed in 18 except in the present work the precursor CuSO4·5H2O was replaced by Cu(NO3)2·H2O. In the system containing sulfate, the first crystalline phase was monoclinic Cu4SO4(OH)6·H2O as observed in 1.5 h sample. These crystals were gradually reduced to form Cu2O nanocrystallites, which underwent aggregation to form spherulites. However, the Cu2O crystals were further reduced quickly to Cu. For example, in 2 h sample, the ratio of Cu2O to Cu was almost 1 : 1, and in 12 h sample, Cu was the only crystalline phase. In the present work using copper nitrate as the precursor, on the other hand, Cu2O/PVP spherulites were the only product in 1.5 h to 6 h samples. The 12 h sample contained a small proportion of Cu, indicating that Cu2O/PVP spherulites formed quickly and were much more stable in the nitrate system. The Cu content increased gradually when the reaction time was extended. However, even in 96 h sample, the main phase was still Cu2O, as discuss below.The synthesis conditions of this work were almost identical to the conditions used for growth of Cu icosahedra,3)2·H2O is very similar with the spectrum of pure DMF,26 with additional contribution from PVP. The latter increases the peak intensities of CH2 (2987 cm−1), CH , and CN (1255 cm−1). In the FTIR spectra of 2 h and 6 h solid samples, the C PBM data was replaced with SVG by xgml2pxml:<glyph-data id="z.dbd" format="PBM" resolution="300" x-size="8" y-size="10" xml:space="preserve">00000000000000000000000000000000111111110000000011111111000000000000000000000000</glyph-data><svg xmlns="http://www.w3.org/2000/svg" version="1.0" width="13.200000pt" height="16.000000pt" viewBox="0 0 13.200000 16.000000" preserveAspectRatio="xMidYMid meet"><metadata>Created by potrace 1.16, written by Peter Selinger 2001-2019</metadata><g transform="translate scale" fill="currentColor" stroke="none"><path d="M0 440 l0 -40 320 0 320 0 0 40 0 40 -320 0 -320 0 0 -40z M0 280 l0 -40 320 0 320 0 0 40 0 40 -320 0 -320 0 0 -40z"/></g></svg>O peak (1658 cm−1) almost disappears, while all hydrocarbon bonds and C−O bond (1087 cm−1) still exist. This result indicates successful removal of the solvent DMF during extracting the precipitates, while the solid spherulites still contain PVP. The fact that the CO peak disappears and the C–O peak remains can be attributed to the formula change of PVP when reducing Cu2+ and the combination of PVP with Cu cations. A similar situation was observed previously in an Ag/PVP system.27 Notably a new peak in these FTIR spectra at 600 cm−1 emerges and is assigned to crystalline Cu2O. Consequently, the particles are Cu2O/PVP composite micro-spherulites. To further confirm the involvement of PVP, SXES was performed to examine light elements in the spherulites. The spectrum is displayed in Fig. S2 in the ESI.2O.The spherulites are unlikely to be monophasic or single crystalline, but composed of inorganic nanocrystals and organic substrates. Spectroscopic techniques were applied to study the composition and chemical bonding in the spherulites. To reveal the inner structure of the spherulites, SEM images of cross sections of the particles were recorded as shown in 2O structure when viewing down the [001] direction. It is obvious that the [100] zone axis of Cu2O is parallel to the radial direction in the spherulite. The detailed structure of the spherulites was revealed by HRTEM images. As seen in a HRTEM image in d-spacings corresponding to the fringes are about 2.15 Å, which can be indexed to the (200) planes of the cubic structure of Cu2O. Consequently, the produced spherulites contain self-oriented Cu2O nanocrystallites embedded in a PVP substrate.TEM observation was carried out to characterise the structure of spherulites. 3)2 and PVP was stirred for 15, 30 and 45 min in an oil bath at 150 °C and evaporated on hotplate. Subtle greenish brown residues at these reaction times were scratched off the beaker wall and were characterised using SEM and TEM. d-spacings from these nanocrystallites are about 2.14 Å, which can be indexed to the (200) planes of the Cu2O structure. Importantly, these nanocrystallites are randomly oriented, indicating that the interaction between the nanocrystallites is not strong enough to induce self-orientation as observed in spherulites . Presumably, the whole particles of spherulites are neutral. If all the nanocrystallites as dipoles line up along the radial directions guided by an electric field from the negatively charged core,28 all the Cu2O dipoles would turn their positive ends towards the core and their negative ends to the surface. The whole surface of the spherulites would be therefore negatively charged and would adsorb dye molecules with an opposite charge  and Congo red  in aqueous environment, while no interaction occurred with alginate (negatively charged due to acidic groups) (Fig. S6c to 6f in the ESIFor surfactant agglomeration experiments, Cu2+ to Cu2O as a reducing agent, PVP also served as nucleation site and agglomeration agent to hold Cu2O nanoparticles. Furthermore, its soft matter property allows nanocrystallites to shift and rotate locally, enhancing self-orientation of the nanocrystallites.PVP plays an important role during the growth of spherulites. After reducing Cu2O spherulites from different growth times, we now are able to propose an overall growth mechanism (Based on the analysis of Cuechanism .2+ cations, NO3− ions and PVP co-exist in DMF solution at 150 °C (Initially, Cut 150 °C . Commerc2+ cations are reduced by PVP to form Cu2O nanocrystallites. During this time, NO3− anions, unlike SO42−,18 do not form crystalline phase with Cu2+. Their decomposition can also accelerate the process of Cu2+ to Cu2O.29 PVP polymer serves as nanoparticle dispersant, wrapping the nanocrystallites, producing PVP/Cu2O microscale spheres, as witnessed in 2O nanocrystallites in these spheres are small with a low crystallinity and have random orientations. At this stage, dipolar field is not generated in the nanocrystallites (Shortly after, Cutallites . Some sutallites . The den2O nanocrystallites leads to the self-orientation (2O nanocrystallites in the small spheres quickly line up along the radial directions with their positive ends facing to the core and negative ends pointing to the surface of the spherulitic particles. To achieve this, all the nanocrystallites are separated without directly merging as often observed in attachment growth of nanomaterials,30,31 and are able to sift and rotate locally in the PVP soft matter substrate. The alignment of Cu2O nanocrystallites lead to the formation the needle-like bundles (The interaction between the negative core and surrounding Cuentation . The Cu2 bundles . Finally bundles .+ to Cu, as seen in 2O nanocrystallites to Cu nanocrystallites by PVP, will the dipolar fields in nanocrystallites vanish because Cu nanocrystallites would never develop dipolar field and the spherulite morphology disappears.Additionally, PVP as a polymerized surfactant helps to hold the spherulite structure while itself as a weak reducing agent can further reduce Cu3,5 or synthetic spherulites.5,6 On the other hand, formation of spherical aggregates of disordered materials without charged cores is an important step in reversed crystal growth. These particles often undergo surface recrystallisation into single crystalline polyhedral shell as demonstrated in several examples. Nanocrystalites of zeolite analcime aggregated with ethylamine into large spherical particles, which underwent surface recrystallisation into icositetrahedral single crystal shells.32 Spherical aggregates of inorganic precursors for zeolite LTA and biopolymer chitosan developed cubic single-crystal shells.33 Aggregates of nanocrystallites of perovskite-type BaTiO3 with polyethylene glycol led to dodecahedral crystalline shell.34 Spherical aggregates of nanocrystallites of Cu and PVP underwent surface recrystallisation into pseudo-icosahedral shells.18 This surface recrystallisation of polycrystalline spheres seems to be quite common.35 However, such a surface recrystallisation process was never found in any type of spherulites. The size of the unreduced Cu2O crystallites maintains at nanoscale even the reaction time was lengthened to 96 h.An important character of spherulites is that the nanocrystallites are manacled by the electric field in the core and are not parallel to each other with less freedom for local shift and rotation. A direct effect of this property is that a surface recrystallisation into single crystalline polyhedral shell would not take place in the spherulites, no matter whether they are naturally occurring spherulites,2O/PVP composite spherulites has been discussed in detail. PVP shows its multifunction, reducing Cu2+ to Cu+ as a reducing agent and offering confined space for growth of nanocrystallites of Cu2O, but restricting further growth. The soft matter property of PVP allows the embedded nanocrystallites to orient themselves. PVP is also the main component in the cores of the composite spherulites, generating a negative charge centre. The interaction of this central electric field and the Cu2O nanocrystallites as dipoles is the driving force for the radially directed self-orientation of the nanocrystallites. This special microstructure leads to a negatively charged surface of spherulites and a high stability of nanocrystallites without further surface recrystallisation into single crystal polyhedral shells. The present work throws light on the investigations of spherulites, polymer assisted crystal growth and the impact of dipolar field in nanocrystallites.The formation mechanism of CuW. H. Sun is the principal researcher who carried out the experiments and data analysis. He also prepared the draft of the manuscript. W. Z. Zhou supervised this work. He also contributed to the discussions of the experimental results and preparation of the manuscript.There are no conflicts to declare.RA-012-D2RA03302J-s001


To describe national antibiotic prescribing for acute gastroenteritis (AGE).Ambulatory care.We included visits with diagnoses for bacterial and viral gastrointestinal infections from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey  and the IBM Watson 2014 MarketScan Commercial Claims and Encounters Database. For NAMCS/NHAMCS, we calculated annual percentage estimates and 99% confidence intervals (CIs) of visits with antibiotics prescribed; sample sizes were too small to calculate estimates by pathogen. For MarketScan, we used Poisson regression to calculate the percentage of visits with antibiotics prescribed and 95% CIs, including by pathogen.Yersinia , Campylobacter , Shigella , typhoid or paratyphoid fever , and nontyphoidal Salmonella . Antibiotics were prescribed for 12.3%  of visits for viral gastroenteritis.We included 10,210 NAMCS/NHAMCS AGE visits; an estimated 13.3%  resulted in antibiotic prescriptions, most frequently fluoroquinolones , nitroimidazoles , and penicillins . In NAMCS/NHAMCS, antibiotic prescribing was least frequent in emergency departments . Among 1,868,465 MarketScan AGE visits, antibiotics were prescribed for 13.8% , most commonly for Overall, ∼13% of AGE visits resulted in antibiotic prescriptions. Antibiotics were unnecessarily prescribed for viral gastroenteritis and some bacterial infections for which antibiotics are not recommended. Antibiotic stewardship assessments and interventions for AGE are needed in ambulatory settings. Annually, ∼75 million diarrheal illnesses result in visits to US healthcare providers, primarily in outpatient settings. Given that self-limited viral and bacterial illnesses are the most common causes of acute gastroenteritis, antibiotics are not recommended for most patients. Unnecessary antibiotic use contributes to antibiotic resistance, which has been increasing among enteric and other pathogens.Acute gastroenteritis (AGE) causes ∼179 million episodes of acute diarrhea each year in the United States. We describe rates of antibiotic prescribing for AGE in the United States.Better understanding antibiotic prescribing practices for enteric infections could inform antibiotic stewardship efforts. National antibiotic prescribing for AGE has not been well described. Studies in select populations have reported antibiotic prescribing rates of 10%–25% for acute diarrhea.International Classification of Diseases, Tenth revision, Clinical Modification (ICD-10-CM) codes. We chose NAMCS and NHAMCS data for their national representativeness. We used MarketScan data to describe antibiotic prescribing according to variables for which NAMCS/NHAMCS sample sizes were too small to generate reliable estimates and those not available in NAMCS/NHAMCS.We used 2006–2015 National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) data and a comparable year (2014) of data from the IBM Watson MarketScan Commercial Claims and Encounters Database (henceforth “MarketScan”). Study periods were chosen to predate adoption of  NAMCS collects data on visits to office-based practices; all specialties except radiology, pathology, and anesthesia are included. NHAMCS collects data on visits to emergency and outpatient departments in nongovernment general and short-stay hospitals. As recommended by NCHS, we excluded NAMCS data from community health centers and NHAMCS data from outpatient departments because they were not available during the entire study period . Both NAMCS and NHAMCS capture patient demographics, physician diagnoses, services, medications, and other treatments.NAMCS and NHAMCS are national surveys designed and implemented by the National Center for Health Statistics (NCHS). The publicly available data are nationally representative, based on systematic random samples of ambulatory medical care visits, using a multistage probability sampling design. We used the “outpatient” and “outpatient prescription” tables and defined a visit as the unique combination of enrollee identification number, service date, and service location. During 2014, the sample size was 47 million covered lives.MarketScan is a convenience sample of deidentified medical claims for persons aged <65 years with private medical insurance.The National Center for Emerging and Zoonotic Infectious Diseases’ human subjects’ advisor deemed these deidentified NAMCS/NHAMCS and MarketScan data nonhuman subjects; institutional review board review was not required.International Classification of Diseases, 9threvision, Clinical Modification (ICD-9-CM) code for ≥1 of the following: bacterial gastrointestinal infection (excluding cholera and Clostridioides difficile), viral gastroenteritis, vomiting, or diarrhea (Supplementary Table 1 online). We restricted the NAMCS/NHAMCS analysis to new problems (duration <3 months), captured by the “major reason for the visit” variable. MarketScan does not capture problem duration.We defined an AGE visit as one with an 2 online). Antibiotics are almost always indicated for tier 1 diagnoses. Antibiotics may be indicated for tier 2 conditions, including AGE. Antibiotics are generally not indicated for tier 3 conditions. We excluded AGE visits that included a tier 1 ICD-9-CM code. No NAMCS/NHAMCS AGE visits had another tier 2 code. In MarketScan, 1.9%  of AGE visits also had an ICD-9-CM code for “other and unspecified noninfectious gastroenteritis and colitis,” which we did not include in our AGE definition. Moreover, <0.25% of MarketScan AGE visits had tier 2 codes other than “other and unspecified noninfectious gastroenteritis and colitis.”For NAMCS and NHAMCS, we used all available ICD-9-CM codes . For MarketScan, we included all diagnosis codes for each claim associated with a single visit. We adapted a previously described tiered algorithm to assign ICD-9-CM codes to tiers based on the likelihood of requiring antibiotics . For NAMCS/NHAMCS, we extracted antibiotics from data on medications ordered, provided, or prescribed at each visit. Route of antibiotic administration was not available in NAMCS/NHAMCS, and we excluded antibiotics only available in topical formulations. For MarketScan, all available nonparenteral prescription drug claims were linked to the most recent outpatient visit within the preceding 3 days.We coded antibiotic prescriptions based on their generic components and therapeutic classes using Lexicon Plus We analyzed antibiotic prescribing according to age group , sex, visit setting , and ICD-9 codes . For NAMCS/NHAMCS, we also analyzed antibiotic prescribing according to variables not available in MarketScan: race/ethnicity, insurance type, fever (temperature ≥38.3°C or 100.9°F) at the visit, and whether a complete blood count (CBC) was ordered. For MarketScan, we also analyzed antibiotic prescribing according to variables not available in NAMCS/NHAMCS (stool culture orders) or for which NAMCS/NHAMCS sample sizes were too small to generate reliable estimates . We used current procedural terminology (CPT) codes 87045, 87046, and 87427 to identify MarketScan visits where stool cultures were ordered.2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea (“IDSA guidelines”) for conditions with recommended antibiotics. Antibiotics were considered “concordant” with 2017 IDSA guidelines if the class included a first choice or alternative recommendation. For shigellosis, IDSA guidelines stipulate “if susceptible” for trimethoprim-sulfamethoxazole and ampicillin. We calculated concordance assuming all visits with these antibiotics were either concordant or discordant to determine upper and lower estimates, respectively.We assessed concordance of antibiotic prescriptions with  We report estimates that met established standards of reliability and precision . We compared the weighted mean percentage of visits with antibiotics prescribed between strata using the χ and an α level of .01, as recommended by the NCHS. For the MarketScan analysis, we used Poisson regression to calculate 95% confidence intervals.We performed all statistical analyses using SAS version 9.4 software . We used 10 years of NAMCS/NHAMCS data to have a sufficient sample for reliable weighted estimates. We calculated national annual percentage estimates and confidence intervals using complex sample methods and sampled visit weights.3 online). These data equate to a weighted percentage of 13.3%  and, nationally, an estimated 11.1 million AGE visits  with antibiotics prescribed during the 10-year period.Antibiotics were prescribed during 1,162 of 10,210 unweighted AGE visits during 2006–2015 , nitroimidazoles , penicillins , and cephalosporins   and was least frequent among children aged 5–17 years  (Table oF) compared with those who were afebrile or had no temperature recorded during the visit . Antibiotic prescribing did not differ based on whether a CBC was ordered  , followed by office settings  and emergency departments   than those without at 13.3%  , Campylobacter , Shigella , typhoid or paratyphoid fever , nontyphoidal Salmonella , Escherichia coli , and unspecified or other bacteria . Overall, 12.3%  of visits coded as viral gastroenteritis had antibiotics prescribed. Although not included in our definition of AGE, 19.4%  of visits coded as “other and unspecified diarrhea from noninfectious causes” had antibiotics prescribed (Table 1 and 2 online).Visits coded for the following pathogens most frequently had antibiotics prescribed: Salmonella infections, E. coli infections, unspecified or other bacterial AGE, ill-defined intestinal infections, and viral gastroenteritis  and 84.4%  of visits for typhoid and paratyphoid fever . For Shigella, the lower estimate of concordance was 63.4%   and the upper estimate was 90.2  . Visits for Yersinia infection were too uncommon to evaluate concordance.Among AGE visits with antibiotic prescriptions, antibiotics were concordant with 2017 IDSA guidelines for 85.2%  of visits for E. coli infections (21%) and viral gastroenteritis (12%). Antibiotic prescribing occurred at only one-third of visits coded as typhoid or paratyphoid fever, despite antibiotics being indicated for these infections. Antibiotics prescribed were most often concordant with current IDSA guidelines but varied by pathogen. Our findings underscore the need for antibiotic stewardship assessments and interventions for AGE in ambulatory settings.Using national databases of ambulatory medical visits, we found that ∼13% of AGE visits had an antibiotic prescribed. AGE visits in medical offices and urgent-care centers were significantly more likely to have antibiotics prescribed than those in emergency departments. The most frequently prescribed antibiotic classes were fluoroquinolones, nitroimidazoles, and penicillins. Antibiotics were most often prescribed for visits coded for a bacterial infection or when visit features suggested a bacterial infection. Antibiotics were often prescribed for conditions that do not generally require antibiotics, including  Although vomiting is an uncommon clinical manifestation of bacterial enteritis, antibiotics were prescribed for ∼10% of NAMCS/NHAMCS visits coded for vomiting without diarrhea, or ∼3.6 million visits over the 10-year study period. Similarly, antibiotics were prescribed for 12% of MarketScan visits coded as viral gastroenteritis.We identified antibiotic prescribing patterns that were discordant with clinical guidelines. IDSA recommends empiric antibiotic therapy for diarrhea when clinical features of bacterial enteritis are present in certain hosts. including fever, diarrhea without vomiting, and visits with a stool culture order. Overall, prescribing was less frequent than has been reported previously; a small, prospective study published in 2003 found 93% of patients with presumed bacterial enteritis were prescribed antibiotics. However, antibiotic prescribing was higher than optimal (13%) for visits without a stool culture order. Although stool cultures are not universally indicated in the evaluation of infectious diarrhea, antibiotic treatment without a stool culture is problematic because it eliminates the ability to choose antibiotics based on culture and antibiotic susceptibility results. Resistance to commonly prescribed antibiotics is increasing among bacterial enteric pathogens.Consistent with previously published data, antibiotic prescribing was higher among visits for illnesses with features more suggestive of bacterial enteritis than those without,Yersinia, 46.7%). Prescribed antibiotics were sometimes discordant with recommended antibiotics based on 2017 IDSA guidelines, although our analysis does not include data after these were published. Clinical trials have not shown that antibiotic therapy shortens the duration of illness for noninvasive Yersinia infection. Penicillins, which are not recommended for Yersinia infection, were the most frequently prescribed antibiotic class. Antibiotic prescribing was also high for nontyphoidal Salmonella infection (30.7%) and E. coli infection (25.8%). Antibiotics can prolong Salmonella shedding and are generally only recommended for patients at increased risk of invasive disease. Antibiotics are generally contraindicated for diarrheal illness caused by E. coli, aside from enterotoxigenic E. coli, because they can increase life-threatening complications of STEC infection.Antibiotic prescribing was relatively high for visits coded for bacterial infections that usually do not require antibiotics .Clostridioides difficile infection, and contribute to the development of antibiotic resistance. Fluoroquinolones were the most frequently prescribed antibiotic class overall and for viral gastroenteritis, prescribed for an estimated 3.2 million visits during the 10-year study period. Fluoroquinolones have been associated with serious adverse events, including tendon rupture and cardiac conduction abnormalities. Providers prescribing antibiotics for AGE should follow treatment guidelines, consider potential risks and benefits to the patient, and tailor antibiotics based on susceptibility testing results.Antibiotic misuse can cause allergic reactions, dysbiosis, and  more work is needed for AGE in outpatient settings. In both analyses, prescribing was lowest in emergency departments, despite illness acuity likely being higher. Providers in medical offices and urgent-care centers may especially benefit from further evaluation of antibiotic prescribing practices and antibiotic stewardship related to AGE. Physicians are more likely to prescribe antibiotics for acute diarrhea when they believe patients expect them. Public health messaging for patients should emphasize that most diarrheal illnesses do not require antibiotics.Although antibiotic stewardship efforts have been successful in hospital settings and for viral respiratory infections, We did not find differences according to insurance type within NAMCS/NHAMCS. MarketScan only includes patients with commercial health insurance and is not nationally representative.NAMCS/NHAMCS and MarketScan findings were generally similar when overlapping analyses were possible. However, AGE visits among children were approximately twice as likely to have an antibiotic prescription in MarketScan compared with NAMCS/NHAMCS (21% vs 11%), although most pediatric gastroenteritis is viral. These data sets differ regarding period, insurance types, geographic catchment, and inclusion of urgent care settings, factors that have previously been associated with antibiotic prescribing. We excluded this code from our AGE definition because we assumed that it was more likely used for noninfectious than infectious gastroenteritis. Fully elucidating the somewhat high prescribing for this code was beyond the scope of this analysis.Our analysis relies on billing codes without the possibility to clinically validate AGE diagnoses. Future analyses might explore how well AGE diagnostic codes correspond with clinical diagnoses, including whether this varies according to provider specialty, practice setting, adoption of ICD-10 codes, or availability of culture-independent diagnostic tests. Previous studies of hospitalized adults and children with culture-confirmed bacterial enteritis found that “other and unspecified diarrhea from noninfectious causes” was sometimes used.3 online). For both analyses, we made assumptions to assign the primary indication for antibiotic therapy; antibiotics may have been prescribed for conditions other than AGE. We may have underestimated bacterial enteritis diagnoses given that cultures need time to grow and are not perfectly sensitive; we did not have stool culture results. Our study period largely predates uptake of commercial multiplex stool polymerase chain reaction panels with rapid diagnostic capabilities. Antibiotics may have been prescribed before a diagnostic test result was obtained or an ICD-9-CM code was assigned. We could not determine whether antibiotics were indicated because host factors  and illness severity could not be reliably determined. MarketScan relies on a convenience sample of insured patients aged <65 years and is not generalizable; assumptions were made to generate “visits” from insurance claims data, practice settings were based on facility codes, and prescriptions were not captured if they were filled >3 days after the visit or if they did not generate an insurance claim .Our findings have several limitations. These older data may not represent recent trends; interpreting NAMCS/NHAMCS results by year is difficult given the wide, overlapping 99% confidence intervals (Supplementary Table We estimate that 13% of AGE visits nationwide resulted in antibiotic prescriptions. Despite likely lower illness acuity, patients treated for AGE in medical offices and urgent care centers were significantly more likely to be prescribed antibiotics than those treated in emergency departments. Although most visits did not result in inappropriate use of antibiotics, antibiotics were prescribed for viral gastroenteritis and for some bacterial infections for which antibiotics are not recommended. Our findings suggest that antibiotic stewardship assessments and interventions are needed for AGE in ambulatory settings to reduce unnecessary antibiotic use and improve patient care.


PA-2018 = 3.06, p < 0.001; βPA-2019 = 1.43, p < 0.05; βPA-2020 = −0.43, p > 0.05; βPA-2021 = 2.82, p < 0.001), while SL and QoL were characterised by an inverted ‘U’ curve . SB was significantly and negatively associated with QoL after 2020, with 2020 identified as the inflection point for the change in SB . Using a time re-allocation technique to treat the 2021 data, reallocating time from SB to PA or to SL predicted improvements in QoL of preschoolers . The study provided useful information on the temporal trends in PA, SB, SL, and QoL of preschoolers over four years. Additionally, these data provided insights into how changes in QoL are predicted by changes in duration in the 24-h movement behaviours.Studies show that the quality of life (QoL) of preschoolers is closely related to physical activity (PA), sedentary behaviour (SB), and sleep (SL). Yet many researchers looked at these 24-h movement behaviours as behaviours that are independent of one another when examining the association of QoL with these behaviours. The main purpose of the present study was to describe the temporal trends in PA, SB, and SL in preschoolers and the concomitant association with QoL of children. Annual cross-sectional data on QoL and 24-h movement behaviours of 8045 Singaporean preschoolers were collected from 2018 to 2021. Compositional analysis, linear regression, and isotemporal replacement approaches were used to examine changes in PA, SB, and SL from 2018–2021 and how these changes were associated with QoL. Temporal trends in movement behaviours showed that PA and SL decreased after 2020. During 2018–2021, the association of PA and QoL in preschoolers was characterised by a ‘U’ curve (β Quality of life (QoL) is an important concept and attribute in the field of medicine and public health , which iHealth-related QoL is also central to paediatric-related practice , and varPrevious studies reveal that increasing PA improves physical functioning, psycho-emotional functioning, and overall QoL at all ages . PA is sCurrent international policy and research trends emphasize the important influence of PA, SB, and SL on QoL. It is noteworthy that PA, SL, and SB make up a 24-h day of interdependent movement behaviours, and an increase in the time spent on one behaviour could necessarily lead to decreases in other behaviours . Even th(1)To investigate the changes in 24-h behaviours  of preschoolers from 2018–2021 using CoDA;(2)To examine the trends of association between 24-h behaviours and QoL of preschoolers from 2018–2021 based on linear regression models;(3)To predict changes in QoL by re-allocating time between PA, SB, and SL behaviours using an isotemporal substitution analysis model with PA, SB, and SL behaviours from data collected in 2021.Therefore, the present study has three aims. They are:In the accomplishment of these objectives, the use of CoDA over a period of four years offers an alternative to the traditional research approach of examining the relationship between 24-h behaviour and quality of life, thereby offering fresh insights to the relationships between preschoolers’ PA, SB, SL, and QoL. Additionally, the isotemporal substitution model provides useful information about the quantum of benefit for substituting one behaviour for another.The study is based on the International iPreschooler Surveillance Study Among Asians and otheRs (IISSAAR), a project that investigates preschoolers’ digital and non-digital behaviours outside of school, including digital media use, non-digital media SB, SL, PA, and QoL. Repeated cross-sectional parent-reported survey responses were collected from 2018 to 2021. Inclusion criteria were parents with preschoolers aged 2 to 5 years old enrolled in one of the anchor operator preschools or kindergartens in Singapore. These preschool operators operated under a private–public enterprise arrangement called the Anchor Operator Scheme . The priCross-sectional parent-reported survey responses were collected from 2018 to 2021, and the periods of data collection in each year are as follows: For year 2018, data collection were between the periods of March and August. For year 2019, data collection commenced in March and ended in September. For year 2020, data collection was deferred to August due to the emergence of COVID-19 at the beginning of the year. Completion of data collection was in November that year. For year 2021, data collection commenced in April and concluded in July.®) and Pediatric Quality of Life Inventory (PedsQL™). A total of 9069 complete responses were collected, of which 8045 (88.7%) were retained after further data cleaning. The data sorting process is detailed in Eligible parents who gave their informed consent were directed to an online questionnaire package that comprised the Surveillance of digital Media hAbits in earLy chiLdhood Questionnaire  commonly use accelerometers for the data collection on PA and SB, but this approach and concept are equally applicable to subjective reporting of time-use ,28. The ® is not a psychometric assessment tool. Rather, it was developed to solicit, in particular, information from adult parents about the digital  and non-digital media  habits of their preschool-aged children on a weekday and on a weekend. Parents were also queried about their attitudes and concerns towards child digital media use and their awareness and practice of child media use guidelines. SMALLQ® is made up of three segments: (I) Digital media use by parent and child, (II) Child’s non-digital behaviours, and (III) Child and parent information [The SMALLQormation . A copy ®—these were three experts in early childhood, an expert in construction of online questionnaires, three preschool teachers, and five parents with children aged below 6 years old, in accordance with the guidelines promoted by Boynton and Greenhalgh [® was guided by the seven-step AMEE framework—Guide No. 87 [® were framed to solicit information particularly about the content , context , and dose  of digital media use based on the conceptual understanding of screen media parenting proposed by O’Connor and his colleagues [®.Multiple stakeholders were involved in the development of the SMALLQeenhalgh . The deve No. 87 . The sevlleagues . Five pa® were then face- and content-validated by four independent experts based upon the criteria of representativeness, clarity, and relevance [®XM and was pre-tested on 137 parents of preschool children. None of the parents reported any difficulty in answering or responding to the questionnaire items. The development and validity of SMALLQ® was described previously by the authors [The questionnaire items in SMALLQelevance . Thereaf authors .The Cronbach values for PA over the four years were as follows: 0.808 for 2018, 0.814 for 2019, 0.776 for 2020, and 0.801 for 2021. The Cronbach values for SB over the four years were as follows: 0.889 for 2018, 0.863 for 2019, 0.846 for 2020, and 0.766 for 2021. The Cronbach values for SL over the four years were as follows: 0.733 for 2018, 0.717 for 2019, 0.642 for 2020, and 0.576 for 2021. A Cronbach’s alpha of 0.70 is commonly cited as an acceptable threshold . TherefoParents were asked in the questionnaire to recall the durations of different activities of their children. An example of a recall question on time spent on physical activity is: ‘In the last 7 days, how much time did your child spend (in a day) on outdoor physical play ?’ An example of a recall question on time spent on SB is: ‘In the last 7 days, how much time did your child spend (in 1 day) using digital media for education/learning .’ An example of a recall question on sleep is: ‘In the last 7 days, what was the average duration of your child’s night-time sleep?’.® into PA, SB, and SL. Helping with household chores, indoor play, and outdoor play were grouped as PA. On-screen activities  and non-digital media sedentary activities  were classified as SB. Naps and night-time sleep were grouped as SL  is a widely reported health-related quality of life (HRQoL) instrument, and the acute 7-day recall parent-reported version was used . The parIn addition, the QoL questionnaire was divided into several versions according to age groups, such as 2–4 and 5–7 years. Because of the age of preschoolers, the parent proxy report version was chosen for the survey. At the same time, the question “which age group does your child belong to” was used to triage parents, and the corresponding age group questions were presented to ensure the validity of the data entered. The scale is currently used in several countries around the world to monitor children’s health, with Cronbach alpha values for the full 23-item scale approaching 0.90 for self- and proxy-report . SpecifiThe data cleaning process is outlined in Both gender  and age of child were set as covariates for controlling its potential influence in the study analysis.Compositional data analysis (CoDA) is a well-established statistical method that is widely used in research where multiple “components” (variables) are involved ,40. The In recent years, compositional analysis has been used to treat data emanating from several countries, such as time spent on various types of behaviours per day and their impact on health through relative changes in the time spent in these different behaviours . Using CBesides conducting a demographic analysis of PA, SB, and SL of preschoolers in 2018–2021 using ANOVA based on age, gender, and ethnicity, descriptive statistics  based on the features of compositional analysis were also generated ,41. AfteDuring the application of compositional analysis, the temporal component for each behaviour  was used as the independent variable and QoL as the dependent variable. Subsequently, two models were generated by using an isometric log-ratio (ilr) data transformation : (1) We https://www.r-project.org/, accessed on 1 October 2022) [p < 0.05.In the process of data analysis, the demographic analysis was completed through SPSS Version 26.0 , and all other data associated with the compositional analysis were completed through the R program Version 4.2   . For all2018 = 2677, N2019 = 1961, N2020 = 2403, N2021 = 1004). The number of boys and girls among preschoolers in each year of study was relatively even at around a 50% split for each gender; for the covariates, it showed significant differences in mean age (Page < 0.001) across 4 years, but not for gender (Pgender > 0.05). For 24-h behaviours , there were significant differences in SL and SB  across 2018 to 2021, but not for PA (PPA > 0.05) in the 4-year data sample. The relative ethnic distribution of parent respondents in the present study is somewhat similar to the ethnic make-up of the population in Singapore . Across 2018 to 2021, 65.9% of parent respondents were Chinese, 16.7% were Malay, 11.2% were Indian, 0.3% were Eurasian, and 6.0% indicated others.The descriptive characteristics of the cross-sectional study sample from 2018–2021, and the difference of the characteristics across 4 years are presented in PA = 7.42, p < 0.001; FSL = 5.61, p < 0.001). The trends in 24-h behaviours for PA, SB, and SL of preschoolers from 2018–2021 are illustrated as ternary plots in To better understand the 24-h behavioural changes in children from 2018–2021, compositional analysis was used to process the data. The CoDA helps us to understand the data more spatially, and the ternary plot represents this characteristic well . AnalysilogPA/SL-2018 = 0.33, logPA/SL-2019 = 0.38, logPA/SL-2020 = 0.37, logPA/SL-2021 = 0.36, logPA/SL-2018–2021 = 0.36), the highest was for PA and SB, followed by SL and SB. When the variance of log (PA/SL) is closest to zero in comparison to the other pairs of behaviours, it is indicative that the proportional relationship or interdependence of behaviours is highly present. In the present study, this interdependence is largest between PA and SL and is smallest between PA and SB.The variability of PA, SB, and SL data is displayed in To gain insights into the PA, SB, and SL for preschoolers with different QoL from 2018 to 2021, we grouped QoL into quantiles and calculated the absolute proportions of different time-use in PA, SB, and SL. These are illustrated as standard bar plots in all years < 0.001), respectively, with the explanatory power of 7%, 4%, 3%, and 3%. Specifically, the associations between PA, SB, SL, and QoL varied from year to year. In 2018, preschoolers’ PA time was positively and significantly correlated to QoL, while SL was negatively and significantly correlated to QoL . In 2019, preschoolers’ QoL was positively and significantly correlated to PA time , but not SB or SL. In 2020, preschoolers’ SL time was positively and significantly correlated to QoL, and SB was negatively correlated to QoL . In 2021, PA of preschoolers showed a positive and significant correlation to QoL again, and SB of preschoolers showed a negative and significant correlation to QoL . It is important to note that the associations and significance of each stated behaviour (PA or SB or SL) correlated to QoL are relative to the other two behaviours.The compositional linear regression models for the cross-sectional association analyses for the years 2018–2021 are presented in The changes in estimating beta values for PA, SL, and SB and QoL of each model over the four years are also shown as trend graphs in PA-2018 = 3.06, p < 0.001; βPA-2019 = 1.43, p < 0.05; βPA-2020 = −0.43, p > 0.05; βPA-2021 = 2.82, p < 0.001). Firstly, the association between PA and QoL for preschoolers showed a decreasing trend from 2018 to 2020, with the weakest association in 2020, and the trend changing from positive to negative, and the trend turning positive again in 2021 .Secondly, the association between SL and QoL in preschool children showed an increasing trend from 2018 to 2020, peaking in 2020, with the association turning from negative to positive, and the trend declined again in 2021, with the association turning negative .Thirdly, the negative association between preschoolers’ SB and the QoL increased consistently and was significantly different between 2020 and 2021 (βp < 0.05). From The data and trends of the isotemporal substitution model in 2021 are presented in This study explored the changes in 24-h behaviours of preschoolers and their associations and trends with QoL in 2018, 2019, 2020, and 2021 by using CoDA. To the authors’ knowledge, this is apparently the first study to apply compositional analysis to the combined behaviours of PA, SB, and SL as factors affecting the QoL in preschoolers and plausibly the first study to examine changes in the relationships between 24-h behaviours and QoL in preschoolers using cross-sectional data over four consecutive years. Several seminal findings in the present study are worthy of discussionOur study showed that PA and SL of preschoolers were more closely interdependent on each other than SB. After 2020, SB in preschoolers increased significantly and SL and PA decreased significantly, but in 2021, PA increased, and SB decreased in preschoolers. In the context of Singapore, this was most likely due to the COVID-19 epidemic. This explanation is affirmed by research that shows that preschoolers’ health behaviours changed as a result of epidemic protection policies following the COVID-19 outbreak in 2020, as well as a significant decrease in PA and a significant increase in SB in the United States, Poland, and Canada ,46,47,48Our study showed that the more physically active preschoolers were, the shorter the duration was of SB, and the higher the QoL was of preschoolers. For instance, the PA of preschoolers was significantly and positively associated with QoL in all years except 2020. At the same time, the SL of preschoolers was significantly and negatively associated with QoL in 2018, but significantly and positively associated in 2020, while SB of preschoolers was significantly and negatively associated with QoL in 2020 and 2021. Several studies have shown that increased PA has a positive effect on children’s motor development, executive function, and healthy growth ,51,52, aOur study also showed that preschoolers may first need to ensure adequate SL as opposed to PA to ensure healthy physical and mental development during the period of the COVID-19 epidemic in 2020. The importance of adequate SL in early childhood cannot be disputed. Early childhood is a critical period for the development of self-regulatory abilities  ,60, incrFrom a compositional data analysis perspective, even though SL in preschoolers increased in 2021 relative to 2020 in the present study, the increased SL was not significantly associated with QoL, but it is plausible that SL ‘acted as a as a booster’ to maximize the health benefits of PA. As shown in the isotemporal substitution model of 2021 , preschoFindings from the present study therefore reaffirmed that both PA and SL are important indicators of healthy child development , and thaThe importance of PA, SB, and SL as lifestyle behaviours in young children have come to the fore. The World Health Organization and national bodies have published guidelines for these lifestyle behaviours. Mainly, these guidelines provide daily recommendations for PA and SL for children and emphasize a reduction of SB ,66,67,68The present study has several limitations. Foremost, in order to obtain a larger sample size, the data on preschoolers’ PA, SB, and SL and QoL were all parent-reported using questionnaires, where parent responses were subjective and prone to recall bias and social desirability bias. Nonetheless, recall bias was minimized by having parents recall PA, SB, and SL and QoL of their children over a period of 7 days. Social desirability bias was also minimized by assuring parents of their anonymity. Another limitation is that data collected in 2020 was at a different time point of the year compared with data collected in 2018, 2019, and 2021. It is not known if there are temporal variabilities in PA, SB, and SL of preschoolers’ issues that remain unaddressed and await future research. Nonetheless, future research on the 24-h behaviours of PA, SB, and SL should employ a combination of subjective (appropriately developed questionnaires) and objective (such as accelerometers) methods ,73 for aAs the present study involved cross-sectional data of lifestyle behaviours of preschool children and their QoL over four consecutive years in 2018, 2019, 2020, and 2021, only associations among the variables could be elucidated and cause-and-effect explanations remain elusive. The causal effects of 24-h movement behaviours and preschoolers’ QoL need to be further explored with longitudinal studies. Future studies on different forms of non-screen SB and light physical activity, such as eating during family mealtimes or sitting during transportation, that occur during a 24-h day and not addressed in the present study, are worthy of research attention.Overall, 24-h behavioural changes in PA, SB, and SL in preschoolers were significantly associated with their QoL, but the specific association varied depending on the different healthy and hygienic environments across the four years, with the PA and SL of preschoolers decreasing and SB increasing, relatively, after the COVID-19 outbreak in 2020. Between 2018 and 2021, the QoL of preschoolers showed a positive “U-shaped” curve in relation to PA and an inverted “U-shaped” curve in relation to SL, with 2020 as the turning or inflexion point, and SB also showed a significant negative association with QoL after 2020. It appeared that in the present environment , safeguarding PA, increasing SL, and reducing SB in preschoolers is an effective approach to improve the QoL of preschoolers.


Striga hermonthica is one of the major global biotic threats to agriculture in sub-Saharan Africa, causing severe yield losses of cereals. The germination of Striga seeds relies on host-released signaling molecules, mainly strigolactones (SLs). This dependency opens up the possibility of deploying SL analogs as “suicidal germination agents” to reduce the accumulated seed bank of Striga in infested soils. Although several synthetic SL analogs have been developed for this purpose, the utility of these compounds in realizing the suicidal germination strategy for combating Striga is still largely unknown. Here, we evaluated the efficacy of three potent SL analogs  under laboratory, greenhouse, and farmer’s field conditions. All investigated analogs showed around a 50% Striga germination rate, equivalent to a 50% reduction in infestation, which was comparable to the standard SL analog GR24. Importantly, MP16 had the maximum reduction of Striga emergence (97%) in the greenhouse experiment, while Nijmegen-1 appeared to be a promising candidate under field conditions, with a 43% and 60% reduction of Striga emergence in pearl millet and sorghum fields, respectively. These findings confirm that the selected SL analogs appear to make promising candidates as simple suicidal agents both under laboratory and real African field conditions, which may support us to improve suicidal germination technology to deplete the Striga seed bank in African agriculture.The obligate hemiparasite  Zea mays), sorghum (Sorghum bicolor), and pearl millet (Pennisetum glaucum), are important nutrient and livelihood sources for people in the region of sub-Saharan Africa [Striga hermonthica (Striga), which hinders crop production and causes more than 50% cereal yield losses in sub-Saharan Africa [Cereal crops, particularly maize  is an obligate and hemiparasitic plant that parasitizes the root systems of cereals. It is now even becoming a persistent threat to crop production in sub-Saharan Africa, the Middle East, and parts of Asia [Striga causes more than 50% cereal yield losses in sub-Saharan Africa and has already infested up to 40% (approximately 50 million hectares) of cropland in this region [Striga has infested several regions of Africa, the most severely infested countries are Burkina Faso, Gambia, Mali, Niger, Nigeria, Senegal, Togo (West Africa), Ethiopia, Eritrea, Kenya, Mozambique, Malawi, Somalia, Tanzania (East Africa), and Sudan. Beyond those, Striga infestation is gradually spreading to other African countries, such as Cameron, Rwanda, Congo, Burundi, Zambia, and Zimbabwe. The ever-increasing Striga problem incurs an annual loss of US $7–10 billion per annum to the livelihoods of African farmers, and its elevated levels in vast areas will further worsen situations of food insecurity, hunger, and poverty for millions of subsistence farmers [Striga control strategies to minimize the damage is of urgent need for African agriculture. of Asia ,6,7,8. Is region ,10,11, t farmers ,13,14,15Striga, effective control measures are still far beyond success. Production of more than 200,000 tiny (0.3 nm  ×  0.15 nm), light (4–7 μg), and long-lived (>15 years) viable seeds by a single Striga plant, characterized by a complex life cycle and underground parasitism, makes Striga control burdensome [Striga problem, many factors, such as poverty, limited resources, and harsh weather have impeded the control of this parasite in infested areas. In such cases, the key principles for effective control of Striga should be prevention of new seed production, significant reduction in the soil seed bank, and avoiding spreading of seeds from infested to non-infested soils [Despite the debilitating yield losses caused by rdensome ,17. Evened soils ,19,20,21Striga seeds have developed a host detection strategy by perceiving host-released signaling molecules, mainly the phytohormone strigolactones (SLs), which trigger their germination [Striga, the receptors responsible for SL-induced seed germination are Striga hermonthica hyposensitive to light (ShHTLs), a group of α/β s that are assumed to be evolutionarily derived from a karrikin-insensitive2 (KAI2) receptor and to arise through gene duplication with functional replacement by SLs [Striga [Striga seedlings start siphoning off nutrients and water [Striga germination on host-released SLs and host attachment can be utilized as an effective management strategy [Striga seeds’ germination through synthetic SL analogs in the absence of the host leads to the death of germinating seedlings at the latest a few days after germination [Striga seed bank in the infested soils [Striga [Orobanchaceae family, in the past 40 years, its application in real African fields remains contested. Despite the availability of several SL analogs and mimics, the selection of simple SL analogs to be used as potential Striga suicidal agents, especially under field conditions, is still a challenge. In the present study, we selected two potent methyl phenlactonoates (MP3 and MP16) [Striga seed germination, first under laboratory conditions.The tiny mination ,23,24. Smination ,26,27. Tmination . In the t by SLs . Among t [Striga ,31. Rece [Striga , in a sind water ,34. Thisstrategy ,35. The mination ,37. Thised soils ,39,40. H [Striga ,42,43 buStriga germination rate, which is statistically equal to the standard SL analog GR24 (64%) (Striga seeds were more sensitive to a lower concentration of GR24 (0.1 μM) with a maximum germination rate (66%), compared to the two other analogs at the same concentration (34–37%). Interestingly, higher concentrations, (1–10 μM) did not show any significant differences between SL analogs. Next, we applied these SL analogs to Striga seeds collected from Kenya, Burkina, and Niger to account for differences between Striga populations from different origins  on the seeds collected from Kenya and Niger. These results unraveled differences in the sensitivity of Striga populations toward SL analogs but also indicated that the selected analogs could be candidates for testing and realizing the introduction of suicidal germination technology in various parts of Africa.The structures of the selected SL analogs are shown in 24 (64%) . However origins . At a coStriga emergence in comparison to the control treatment (Striga emergence was strongest (97%), followed by Nijmegen-1 (89%) and MP3 (73%). As expected, the application of SLs led to improved growth of the host plant due to lower infection of viable Striga plants. In particular, MP16-treated pots had the same plant heights as non-infested plants. Application of MP3 and Nijmegen-1 also improved plant growth as compared to the control treatment, but to a lesser extent than MP16, which indicated that the latter is the most potent suicidal agent among the selected analogs under greenhouse conditions , followed by MP16 (33 ± 9.8) and MP3 (37 ± 6.7), as compared to the control plot (56 ± 16.4). In other words, treatment with Nijmegen-1, MP16, and MP3 led to a 43%, 41%, and 33% reduction of Striga emergence, respectively (Striga emergence (60%), followed by formulated MP3 (52%) and MP16 (11%)  C. With r16 (11%) D In cont16 (11%) D. These Striga control was first assessed and confirmed using in vitro bioassays. The results showed that MP3, MP16, and Nijmegen-1 are all potent SL analogs inducing Striga seed germination (Striga germination [Striga germination activity at a high dose (1–10 μM). Similarly, we recently reported that MP3 and MP16 exhibit high bioactivity in stimulating Striga seed germination [Striga batches collected from Burkina Faso, Niger, and Kenya. Although all SL analogs (at 1 μM) induce Striga seed germination ranging from 12–20%, this activity level is not as high as we observed in a Striga batch collected from Sudan. This result demonstrates that the sensitivity toward a certain SL analog depends on the ecotype of the Striga population. In addition, it shows the need to have an array of SL analogs to realize the suicidal germination strategy in different parts of Africa. Nevertheless, the results obtained with different Striga populations indicate that the selected SL analogs can be used in different regions of Africa, although with different efficiency levels.The performance of three selected synthetic SL analogs  for Strimination . Previoumination ,44,45, bmination ,37, whicStriga. The maximum 97% reduction in Striga emergence on the application of MP16 showed its potential to be used as a suicidal agent  and reported to be relatively weak . In the al agent . Althougg of MP3 ,39, its  a field . HoweverStriga emergence for both pearl millet and sorghum fields; however, these differences were statistically non-significant  but no significant impact (12–20%) in a sorghum field (clay soil). In the present study, we increased the number of applications from two to four and observed 33–43% and 60–52% reductions in Striga emergence by MP3 and Nijmegen-1 in a pearl millet and sorghum field, respectively. Due to seed dormancy or pre-conditioning requirements, Striga seeds are not synchronous in their germination response to SL analogs; hence, we suggested at least four-time repeated applications of SL analogs for maximum eradication of the seed bank in the infested soil. Then, the compound should reach Striga seeds to induce their germination. The success of the suicidal germination depends on many factors that are not restricted to the frequency and concentration of the suicidal agents but also include the type of the soil, climate conditions, and amount and frequency of rainfall [In field trials, we observed that all selected analogs caused a reduction in nificant . This mireported . In addireported , showingrainfall ,47. In arainfall .Striga. The selected SL analogs will allow the development of further analogs as well as testing and optimizing of formulations and application protocols that aim at depleting the Striga seed bank and increasing food security. Moreover, combining the suicidal germination strategy with resistant crop varieties and/or suitable crop rotation or intercropping will likely alleviate the Striga problem significantly in the infested regions of Africa.In summary, our results demonstrate the potential of the three selected simple SL analogs in combating rac-GR24, MP3, and Nijmegen-1 were synthesized and provided by Prof. Binne Zawanenburg, Radboud University, The Netherlands. The SL analog MP16 was synthesized and provided by Prof. Tadao Asami, University of Tokyo, Japan. The procedure for the synthesis of SL analogs has already been described previously [Striga hermonthica seeds were collected from an infested sorghum field during 2020 in Sudan (Prof. A. G. Babiker), from a maize field during 2018 in Kenya , from a pearl millet field during 2020 in Burkina Faso , and a pearl millet field during 2019 in Niger . Seeds of rice IAC-165 were obtained from Africa Rice, Tanzania (Dr. Jonne Rodenburg). The emulsifier Atlas G-1086, a polyoxyethylene sorbitol hexaoleate, was obtained from CRODA, The Netherlands.The SL analogs eviously ,43,49. SStriga hermonthica seeds was determined by using a previously described procedure [Striga seeds were surface sterilized with 50% commercial bleach for seven minutes, followed by six washing steps with MiliQ water in a laminar fume hood. Then, about 50–100 surface-sterilized Striga seeds were uniformly spread on a glass-fiber filter-paper disc (9 mm), and 12 discs with Striga seeds were put in a Petri dish on sterilized filter paper moistened with 3 mL MiliQ water. The sealed Petri dishes were incubated in the dark at 30 °C for 10 days. On the 11th day, the discs were dried under a laminar flow cabinet, and the SL analogs (50 μL) were applied to each disc with various concentration ranges (10−5 M to 10−7 M). Being very active, the synthetic SL analog GR24 was used as a standard positive control instead of natural SL, which is very scarce in plants, unstable, and difficult to extract. After application, the Striga seeds were induced to germinate in the dark for 24 h at 30 °C. The discs were scanned under a binocular microscope and germinated, and non-germinated seeds were counted by SeedQuant [The germination activity of the selected SL analogs on rocedure ,51. For eedQuant , with a Striga-infested pots under greenhouse conditions, using a highly susceptible rice cv. IAC 165 as a host crop. The SL analogs were applied twice at 1 μM concentration to artificially infested preconditioned Striga pots. After 10 days of application, three one-week-old rice seedlings were planted in each pot, and Striga emergence was counted at 10 weeks after sowing (WAS). A mixture of soil  with sand (3:1 ratio) was prepared [Striga seeds was added to the bottom of a 3-L perforated plastic pot. Then, about 20 mg (~8000) Striga seeds were thoroughly mixed in a 1.5-L soil mixture and added on the top of clean soil in the same pot. The Striga seeds were preconditioned in a greenhouse under hot (30 °C) and moist conditions for 10 days. On the 11th day, each pot was supplied with 500 ml (1 μM) SL analogs, and Striga seeds were allowed to germinate for suicidal death without a host for another 10 days. Then, three one-week-old rice seedlings  were planted in the middle of each pot. The rice plants were allowed to grow under normal growth conditions . After 10 weeks, Striga emergence was observed in each pot and compared with the mock treatment.To further evaluate their bioactivity, we tested the three SL analogs in prepared  and abouStriga-infested pearl millet and sorghum fields, located near the Kouaré research station  of INERA (Institut de l’Environnement et de Recherches Agricoles), were selected. Trials were established in each farmer’s field, following a randomized complete block design with four independent replications using 4 m × 4 m (or 16 m2) plots. Each plot consisted of five (5) ridges/rows, and the distance between ridge/row was 0.80 m; all plots were spaced with four (4) ridges/rows to avoid any SL contamination through run-off. The emulsifier Atlas G-1086 was used to formulate MP3, MP16, and Nijmegen-1. Each SL analog was applied (25 mL/m2 at 400 µM) in formulated form four times in each field after the onset of rainfall (≥10 mm) to make a final concentration of 1 µM. A blank treatment (Atlas-G only) was included as the control. The experimental crops pearl millet  and sorghum  were sown at least one week after the last application. The rainfall was 391.5 mm recorded in 25 days and 617 mm in 27 days during the pearl millet and sorghum growth period, respectively. Plots were weeded twice (15 and 30 days after sowing (DAS)) with hand hoeing before Striga emergence. Then, weeds other than Striga plants were hand-pulled until crop harvest. The emerged Striga plants were counted at 80 DAS, corresponding to the period of maximum emergence of Striga plants in the plots.Next, the suicidal germinating bioactivity of three selected SL analogs was further investigated under naturally infested rainfed farmer’s field conditions in Burkina Faso . Formulat-test were used to analyze the effect of different SL analogs on Striga infestation.Collected data were analyzed using statistical software package R (version 3.2.2) and GraphPad Prism (version 9.1.1). One-way analysis of variance (ANOVA) with the least significant difference (LSD) multiple range test and unpaired


With low binding affinity to C1q and Fcγreceptors, IgG4 is incapable of forming immune complexes and activating the complement pathway, exhibiting a non-inflammatory feature. IgG4 is produced similarly to IgE and is considered a modified reaction to IgE class-switching response under certain conditions. It could also counteract IgE-activated inflammation. However, the clinical significance of IgG4 in allergic diseases is complex and controversial. Three viewpoints have been suggested to describe the role of IgG4. IgG4 can act as a tolerance–inducer to play a protective role under repeated and rapid incremental dosing of allergen exposure in allergen immunotherapy (AIT), supported by allergies in cat raisers and venom desensitization in beekeepers. Another viewpoint accepted by mainstream specialists and guidelines of Food Allergy and Management in different countries points out that food-specific IgG4 is a bystander in food allergy and should not be used as a diagnostic tool in clinical work. However, eosinophilic esophagitis (EoE) investigation revealed a direct clinical relevance between physiopathology and serum IgG4 in cow milk and wheat. These factors indicate that allergen-specific IgG4 plays a multifaceted role in allergic diseases that is protective or pathogenic depending on different allergens or exposure conditions. IgG4 is a subclass of IgG antibody with a unique molecular feature of (Fragment antigen- binding) Fab-arm exchange, allowing  Subclasses of IgG antibodies were discovered in the 1960s , while IIgG4 is conventionally considered non-inflammatory or anti-inflammatory because it cannot form large immune complexes and activate complement component pathways . Thus, iThe clinical significance of IgG4 in allergic diseases is controversial. The earliest recognition of IgG4 in allergies was from Allergen-specific immunotherapy (AIT) data, demonstrating a tolerance-inducing function –16. HoweThe present study provides a comprehensive review of recent studies on IgG4, its structure features, immune biology, interaction with IgE, and different roles in different allergic statuses.L) and one variable domain (VL), while the heavy chain consists of 3 IgG4-specific constant domains  and one variable domain (VH). The variable domains of the heavy (VH) and light chain (VL), with the attached CL and CH1 domains, respectively, formed the ‘fragment antigen-binding region’ (Fab-region), which is highly specific for one epitope. However, unlike other subclasses of IgG composed of two same chains, IgG4 are dynamic molecules that dissociate into two half molecules with one light chain and one heavy chain, then reassemble with another half one. It is called FAE and results in a bi-specific binding antibody  and two heavy chains (-50 kD) paired together  kD and t. The ligantibody , 28. Theantibody , 30, whiantibody . The patvia one molecule  that involve IgE production have similar effects on IgG4 production. However, what predominates the diverging to IgE or IgG4 is still unclear. It was speculated that the allergen stimulus might be the most important factor in initiating the switch to IgE or IgG4. Antibody response to natural cat allergen exposure provides a clear picture, with high IgG4 and low IgE responses in cat raisers. AIT further exhibits a dynamic switch of IgE production to IgG4 production after repeated and rapid increments of allergen exposure. Relevant studies found that IL-10 played a critical role in this shift of IgE to IgG4. oduction , 37. Theoduction . Therebyoduction , which h23 by IgE-allergen complexes  conducted by the Platts-Mills TAE group in children  and ClayThe results of serum IgG4 antibodies on EoE pediatric cases were also intriguing. Thomas’ group found both a high prevalence and very high titers of IgG4 antibodies to the cow’s milk proteins alpha-lactalbumin (Bos d 4), beta-lactoglobulin (Bos d 5), and casein (Bos d 8) as well as to gluten from wheat . The mosThe underlying mechanism is still unclear. Factors such as food particles, and the undiscovered pathway of IgG4 to form an immune complex and activate mast cells, might be possible reasons , 106.bi-specific binding capability in a monovalent manner. A similar condition of IgG4 production to IgE induces the switch of IgE/IgG4. IgG4 plays different roles under different clinical conditions. It works as a tolerance inducer in AIT, cat raisers, and beekeepers, a bystander in food allergy, and a pathogenic role in EOE. The underlying mechanism of these multiple faces of IgG4 in allergic diseases is still unclear and needs further investigation. However, it brings new light to the treatment of allergic diseases as a therapeutical target. For EOE, avoidance of food with positive IgG4 is a good strategy to relieve the symptoms. For some allergies, the application of allergen-specific IgG4 antibodies might be an effective approach to creating a blockade.IgG4 has multiple profiles in allergic diseases due to its unique molecular feature and consequent biology. The FAE results in a dynamic antibody with LQ drafted the molecular feature, impact, and pathogenic role of the IgG4 section. H-YW drafted all remaining sections. All coauthors reviewed and edited the final manuscript. All authors contributed to the article and approved the submitted version.This study was supported by the National Natural Science Foundation of China , the Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents (2016), and the Innovation Team for the Diagnosis and Treatment of Childhood Asthma.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Low awareness of antibiotics and antibiotic resistance may lead to inappropriate antibiotic use and contribute to the problem of antibiotic resistance. This study explored levels and determinants of antibiotic awareness in a rural community in northern Vietnam, through a cross-sectional survey of 324 households in one commune of Ha Nam Province. Awareness and knowledge of antibiotics and antibiotic resistance and determinants were evaluated using structured questionnaires. Most respondents (232/323 (71.8%)) had heard of antibiotics, but fewer could name any antibiotic (68/323 (21.1%)) or had heard of antibiotic resistance (57/322 (17.7%)). In adjusted regression models, antibiotic awareness was lower among those who lived further from health facilities (Odds Ratio (OR): 0.08; 95% Confidence Interval (CI): 0.04–0.19) but higher among those who used interpersonal sources for health information . Antibiotic resistance awareness was lower among those who used private providers or pharmacies as their usual health facility  but higher among those with medical insurance  and those with high media use frequency . Awareness of Antimicrobial Resistance (AMR) was also higher among those who sought health information from official sources  or had overall high levels of health information seeking . In conclusion, communication interventions need to target frequently used media platforms, such as television, as well as key health information providers, such as health workers, as channels for increasing knowledge and changing community antibiotic use behaviour. The discovery of antibiotics a century ago, followed by a golden age of antibiotic discovery between the 1940s and 1960s, revolutionised medical care; however, the evolution of resistance now threatens modern medicine . AntibioConsumer practices and behaviours are key factors accelerating antibiotic resistance globally. Non-prescription antibiotic use is high in Vietnam, with 90% of antibiotic sales in pharmacies being made without a prescription; this is driven strongly by consumer demand . ConsumeInterventions that target community antibiotic use awareness have been shown to have a positive impact, although much of this evidence is drawn from high-income countries. For instance, in the USA, community educational campaigns that aimed at raising antibiotic awareness among parents and clinicians resulted in a larger increase in knowledge and awareness regarding appropriate antibiotic use than in control areas . A systeFew studies on antibiotic awareness have been conducted in LMICs, particularly in rural communities. A 2018 study on antibiotic awareness in five provinces of the central highlands of Vietnam reported that 67.4% of participants had heard of antibiotics, whereas 55.8% had heard of antibiotic resistance . HoweverThe main objective of this study was to assess the levels of awareness and knowledge of antibiotics and antibiotic resistance in a rural community in northern Vietnam and to investigate the determinants of awareness and knowledge, in order to inform the development of interventions.After stratified random sampling, 389 households were selected for data collection, of which 324 households participated, giving an overall response rate of 83.3% and a margin of error of 5.4% for prevalence estimates. Of those that did not participate, three household respondents refused, whereas the other 62 households had no available respondents found during the study period .Individual respondent demographic characteristics are summarized in Access to different media platforms is shown in 2 and not more than 5 km at the widest part) and relatively flat, almost half of respondents (48.6%) said they lived more than 10 min travel time to the commune health centre. These respondents were more likely to be low frequency media users (p < 0.001) and low health information seeking types (p < 0.001).Health workers (97.2%) and television (95.4%) were the most consulted sources of health information, whereas newspapers (13.3%) and books (15.2%) were the least consulted . Though Nearly three quarters of primary respondents had heard of antibiotics (232/323 (71.8%)), but fewer (68/323 (21.1%)) could name any of the 11 antibiotics on our list spontaneously when asked to give the names of any antibiotics they knew. The most well-known antibiotic was ampicillin/amoxicillin, with only (4.2%) having never heard of it, whereas 98.4%, 94.1%, and 92.3% had never heard of colistin, ciprofloxacin, and Augmentin, respectively, even after probing . About oIn unadjusted models , male reDeterminants of antibiotic resistance awareness are presented in This study shows that the overall awareness of antibiotics in this rural community in Vietnam is high (71.8%). However, the spontaneous recall or recognition of names of antibiotics from our list was much lower (21.6%). This inconsistency raises the possibility that respondents’ understanding of the word “antibiotic” when reporting awareness was not in line with its actual meaning, as has been observed in other studies. For example, a study in Malaysia in 2010 found that 33% of the respondents confused antibiotics with painkillers such as paracetamol and aspirin . A similThis study also established that antibiotic resistance awareness is low (18.2%) in this community and driven by similar demographic and media access factors as antibiotic awareness and knowledge. The level of antibiotic resistance awareness is lower than in a recent study in Vietnam, which reported an awareness of antibiotic resistance of 55.8% in a mixed urban¬–rural population; the difference may be due to our study targeting a rural population . A similFactors shown to be associated with awareness of antibiotics in this study, such as demographic characteristics, type of primary facility, location, and use of media, have been reported before ,23. Our In our study, television was the most frequently accessed form of media and also the source used most often for health information. Health workers and community radio were also frequently used sources of health information. We found an association between media use and increased awareness of antibiotics and antibiotic resistance. Other media platforms such as the internet, print media, radio, and SMS are also known to be common sources that individuals use to access information regarding antibiotics. A study in Poland found that the majority of respondents relied on the internet as the source of antibiotic knowledge . LimitedAlthough the study area was small and relatively flat, we found that living more than 10 min of travel time from the usual health facility was associated with lower antibiotic awareness. Further investigation into the relationship between distance from health facility and access to health information revealed that those who lived more than 10 min travel time away were low frequency media users and low health information seeking types. This finding, along with the finding that health workers were important sources of both antibiotic and antibiotic resistance knowledge, highlights the importance of health facilities as sources of health information .This study is among the few studies in LMICs that have evaluated the antibiotic awareness within the general public and particularly rural communities. Moreover, this study incorporated diverse measurement approaches to triangulate antibiotic awareness. The response rate is also relatively high and therefore the risk of selection bias is reduced.This study has several limitations. The results represent one rural community in northern Vietnam and may not be generalizable to other settings in Vietnam. The cross-sectional design limits any conclusions regarding the direction of causal effects. Furthermore, we cannot rule out the possibility of various information biases. For instance, even though data collectors were trained, the interviewers were nurses from the local health centre and may have interpreted the responses using their health knowledge. Respondents may have had difficulty recalling some information related to health-seeking behaviours, and this might have introduced recall bias. Respondents may also have introduced bias by reporting what they thought were desirable/socially-acceptable behaviours. Antibiotics may be known by a mixture of generic and brand names, and the list of antibiotic names we provided might not have been the most commonly used in the area. We are conducting an ethnographic study to explore understanding of antibiotics and the language used to describe them that will aid interpretation of these results and inform future research in this area. Lastly, there might be other unmeasured factors that influence awareness of antibiotics and antibiotic resistance or confound the observed associations.The study was part of a large quantitative cross-sectional household survey conducted with 324 households in a rural commune of Ha Nam Province, northern Vietnam, between 16 July 2018 and 9 April 2019. The commune had a population of 9746 people. The study design has been described in detail elsewhere .Streptococcus pneumoniae, which is carried at higher levels among children under five years old. A sample size of 340 would allow us to estimate prevalence with a 5.2% margin of error with 95% confidence. We sampled 390 households, allowing for a 15% drop-out rate. Nurses from the commune health centre were trained to administer structured questionnaires (in Vietnamese) and to collect information on healthcare seeking behaviour, awareness of antibiotics and antibiotic resistance, and general socio-demographic characteristics. For every household, one adult caregiver responded to the questionnaire. Eligibility depended on giving written informed consent to the study and study procedures, and there were no exclusion criteria for this study.A random sample of households was selected from a household list obtained from the commune health centre. Sampling was stratified so that households with children below five years were oversampled, as one of the study’s primary aims was to collect samples and conduct antimicrobial susceptibility testing for The definitions of dependent and independent variables are provided in Data analysis utilized STATA software version 17.0. Variable categories of similar characteristics were re-grouped into fewer categories to reduce data sparsity. Descriptive statistics were performed to determine the distribution of individual respondent characteristics. Point prevalences were derived for dependent variables, awareness of antibiotics and awareness of antibiotic resistance. Bivariable and multivariable logistic regression models were performed to show associations between media use, health information sources, distance to a health facility, usual health facility, and having a medical insurance card and awareness of antibiotics and antibiotic resistance. Variables such as age, sex, education, occupation, and household wealth were evaluated to be potential confounding factors and were adjusted for in the multivariable logistic models. Bivariable and multivariable linear regression models were run with the continuous antibiotic knowledge and antibiotic resistance scores.Self-reported awareness of antibiotics was high in this study, though knowledge about types of antibiotics and awareness of antibiotic resistance was much lower. The determinants of antibiotic and antibiotic resistance awareness and knowledge included socio-demographic factors  and access to healthcare . Health workers and interpersonal health information sources were associated with more awareness of antibiotics. High use of media  was associated with more awareness of AMR. The complex relationships between knowledge, media access, health information, and behaviour, makes identifying appropriate intervention strategies challenging. Targeting multiple media channels and health information sources, particularly those with the highest access and use, such as television and health providers, is likely to have the highest reach for communication campaigns. Multi-modal campaigns may also be beneficial.