Assessment of spillover of antimicrobial resistance to untreated children 7 to 12 years old after mass drug administration of azithromycin for child survival in Niger: a secondary analysis of the MORDOR cluster-randomized trial.

BACKGROUND: The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aims to understand the risk of spillover of antibiotic resistance to non-target groups in these programs. METHODS: Data was used from a cluster-randomized trial comparing the effect of biannual azithromycin and placebo distribution to children 1-59 months on child mortality. Nasopharyngeal samples from untreated children 7-12 years old were tested for genetic determinants of macrolide resistance (primary outcome) and resistance to other antibiotic classes (secondary outcomes). Linear regression was used to compare the community-level mean difference in prevalence by arm at the 24-month timepoint adjusting for baseline prevalence. RESULTS: 1,103 children 7-12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). Adjusted mean differences in prevalence of resistance determinants for macrolides, beta-lactams and tetracyclines were 3.4% (95% CI -4.1% to 10.8%, P-value 0.37), -1.2% (95% CI -7.9% to 5.5%, P-value 0.72), and -3.3% (95% CI -9.5% to 2.8%, P-value 0.61), respectively. CONCLUSIONS: We were unable to demonstrate a statistically significant increase in macrolide resistance determinants in untreated groups in an azithromycin mass drug administration program. While the result might be consistent with a small spillover effect, this study was not powered to detect such a small difference. Larger studies are warranted to better understand the potential for spillover effects within these programs.

Investigation of a twisting-fused side-pump coupler based on tellurite fiber.

Fiber side-pump couplers can enhance the output power of fiber laser due to their dependable and efficient operation and impressive power handling capability. We developed a tellurite fiber side-pump coupler by twisting and fusing a tapered pump fiber onto a target fiber. The effect of twisting parameters on coupling efficiency was comprehensively investigated through theoretical simulations and experiments. Experimental results exhibited an impressive coupling efficiency of 76.5% and a root mean square stability of 0.086% and 0.091% before and after one month, respectively, driven by an incident pump power of up to 4.2 W.

Constructing Single- or Dual-Layer Biomass Composite Energetic Material through Self-Assembly of Biomass Polyphenol Structural Materials.

High energy and high risk have always restricted the application of materials in the military and civilian fields. To achieve this goal, researchers have studied the structural characteristics and structure-activity relationship of biomass polyphenol material to obtain core-shell biomass polyphenol composite energetic materials through molecular and structural design. The interface structure has a significant impact on the safety performance and thermal stability of energetic materials. The unique advantages of natural biomass polyphenol chemistry (tannic acid and tea polyphenols) include the structural design and performance control of energetic materials. This paper provides a review of the preparation of core-shell biomass polyphenol energetic materials, which involve the use of polyphenols as the shell layer, surface modification layer, and intermediate layer to enhance intermolecular interactions. This approach aims to enhance the thermal stability and reduce the sensitivity. Furthermore, the paper offers suggestions for potential future research directions based on the findings.

Marine Streptomyces-Derived Novel Alkaloids Discovered in the Past Decade.

Natural alkaloids originating from actinomycetes and synthetic derivatives have always been among the important suppliers of small-molecule drugs. Among their biological sources, Streptomyces is the highest and most extensively researched genus. Marine-derived Streptomyces strains harbor unconventional metabolic pathways and have been demonstrated to be efficient producers of biologically active alkaloids; more than 60% of these compounds exhibit valuable activity such as antibacterial, antitumor, anti-inflammatory activities. This review comprehensively summarizes novel alkaloids produced by marine Streptomyces discovered in the past decade, focusing on their structural features, biological activity, and pharmacological mechanisms. Future perspectives on the discovery and development of novel alkaloids from marine Streptomyces are also provided.

Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives.

In this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed that most of the compounds exhibit excellent antitumor activity against epidermal growth factor receptor wild-type lung cancer cells NCI-H1299, A549 and NCI-H1437. Among them, 4b and 4c showed the most prominent inhibitory effects. The half maximal inhibitory concentration (IC50) values of 4b were 4.42 ± 0.24 µM (NCI-H1299), 3.94 ± 0.01 µM (A549) and 1.56 ± 0.06 µM (NCI-1437). The IC50 values of 4c were 4.60 ± 0.18 µM (NCI-H1299), 4.00 ± 0.08 µM (A549) and 3.51 ± 0.05 µM (NCI-H1437). Furthermore, our results showed that 4b and 4c could effectively inhibit proliferation, colony formation and cell migration in a concentration-dependent manner, as well as induce apoptosis in H1299 cells. In addition, 4b and 4c exerted its anti-tumor effects by inducing cell apoptosis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP and downregulating the protein levels of Bcl-2. Based on these results, it is suggested that 4b and 4c be developed as potential new drugs for lung cancer treatment.

Targeted Mass Azithromycin Distribution for Trachoma: A Community-Randomized Trial (TANA II).

BACKGROUND: Current guidelines recommend annual community-wide mass administration of azithromycin for trachoma. Targeting treatments to those most likely to be infected could reduce the amount of unnecessary antibiotics distributed. METHODS: In a cluster-randomized trial conducted from 1 November 2010 through 8 November 2013, 48 Ethiopian communities previously treated with annual mass azithromycin distributions for trachoma were randomized in equal numbers to (1) annual azithromycin distributions targeted to children aged 0-5 years, (2) annual azithromycin distributions targeted to households with a child aged 0-5 years found to have clinically active trachoma, (3) continued annual mass azithromycin distributions to the entire community, or (4) cessation of treatment. The primary outcome was the community prevalence of ocular chlamydia infection among children aged 0-9 years at month 36. Laboratory personnel were masked to treatment allocation. RESULTS: The prevalence of ocular chlamydia infection among children aged 0-9 years increased from 4.3% (95% confidence interval [CI], .9%-8.6%) at baseline to 8.7% (95% CI, 4.2%-13.9%) at month 36 in the age-targeted arm, and from 2.8% (95% CI, .8%-5.3%) at baseline to 6.3% (95% CI, 2.9%-10.6%) at month 36 in the household-targeted arm. After adjusting for baseline chlamydia prevalence, the 36-month prevalence of ocular chlamydia was 2.4 percentage points greater in the age-targeted group (95% CI, -4.8% to 9.6%; P = .50; prespecified primary analysis). No adverse events were reported. CONCLUSIONS: Targeting azithromycin treatment to preschool children was no different than targeting azithromycin to households with a child with clinically active trachoma. Neither approach reduced ocular chlamydia over the 3-year study. CLINICAL TRIALS REGISTRATION: NCT01202331.

Large mode-area all-solid anti-resonant fiber based on chalcogenide glass for mid-infrared transmission.

A large mode-area chalcogenide all-solid anti-resonant fiber has been designed and successfully prepared for the first time. The numerical results show that the high-order mode extinction ratio of the designed fiber can reach 6000, and the maximum mode-area is 1500 um2. The fiber possesses a calculated low bending loss of less than 10-2 dB/m as the bending radius is larger than 15 cm. In addition, there is a low normal dispersion of -3 ps/nm/km at 5 µm, which is beneficial for the transmission of high power mid-infrared laser. Finally, a completely structured all-solid fiber was prepared by the precision drilling and two-stage rod-in-tube methods. The fabricated fibers transmit in the mid-infrared spectral range from 4.5 to 7.5 µm with the lowest loss of 7 dB/m @ 4.8 µm. Modeling suggests that the theoretical loss of the optimized structure is consistent with that of the prepared structure in the long wavelength band.

Chalcogenide GRIN glasses with high refractive index and large refractive index difference for LWIR imaging.

Gradient refractive index (GRIN) materials utilize an internally tailored refractive index in combination with the designed curvature of the optical element surface, providing the optical designer with additional freedom for correcting chromatic and spherical aberrations. In this paper, new GRIN materials suitable for the second (3-5 µm) and third (8-12 µm) atmospheric windows were successfully developed by the thermal diffusion method based on Ge20As20Se60-xTex series high refractive index glasses, where the maximum refractive index difference (Δn) at 4 µm and 10.6 µm were 0.281 and 0.277, respectively. The diffusion characteristics and refractive index distribution of the GRIN glass were analyzed by Raman characterization. Furthermore, the performance of GRIN singlet and homogeneous singlet in the LWIR band (8 µm, 10.6 µm (primary wavelength), 12 µm) was compared, and the results showed that the GRIN singlet had better chromatic aberration correction and unique dispersion characteristics.

Low-loss chalcogenide microstructured optical fibers prepared by eliminating interfaces defects.

The loss of chalcogenide microstructured optical fibers (ChG-MOFs) is generally higher than that of step fibers, mainly due to the immature fiber preform preparation method and strong waveguide defect scattering. Chemical polishing is used to polish mechanically drilled preforms to prepare ChG-MOFs with low defect scattering. Firstly, the scattering loss caused by the defective layer of ChG-MOFs is studied theoretically and experimentally. Then, a single-mode photonic crystal fiber (PCF) was prepared to verify the effect of chemical polishing on reducing fiber loss. The experimental results show that the PCF average loss is reduced from more than 8 dB/m to less than 2 dB/m, and the minimum loss reaches 0.8 dB/m @ 2.7 µm. At the same time, the bending strength of the PCF after chemical polishing is also significantly improved.

Fabrication of a tellurite-fiber-based side-pump coupler based on the tapered-fused method.

In this study, (1 + 1) × 1 side-pump couplers made of tellurite fibers were fabricated and investigated. The whole optical design of the coupler was established on the basis of ray tracing models and validated by experimental results. By optimizing the preparation conditions and structural parameters, the tested component achieved a coupling efficiency of 67.52% and an insertion loss of 0.52 dB. To the best of our knowledge, this is the first time a tellurite-fiber-based side-pump coupler was developed. The fused coupler presented will simplify many mid-infrared fiber lasers or amplifier architectures.

Genomic typing and virulence gene profile analysis of Salmonella Derby from different sources.

Salmonella enterica serovar Derby (S. Derby) is one of the most common Salmonella serovars which can infect poultry, swine, and humans. With the reduction of the sequencing cost and the improvement of sequencing technology, whole genome sequencing (WGS) has become an important method for bacterial determination, molecular investigation, and pathogenic tracing analysis. In this study, we investigated S. Derby isolates from different sources in China using in-silico multilocus sequence typing (MLST), core genome MLST (cgMLST) and whole genome MLST (wgMLST) analysis based on WGS. The results showed that 21 S. Derby strains were divided into 3 STs using MLST analysis, including ST40 (n = 19, accounting for 90.48%), ST71 (n = 1, accounting for 4.76%) and ST8016 (n = 1, accounting for 4.76%). cgMLST and wgMLST analysis categorized the tested strains into 13 cgSTs and 21 wgSTs, respectively. The minimum spanning trees of cgMLST and wgMLST both divided these strains into 3 clusters and 4 singletons. In addition, virulence gene profiles of S. Derby isolates were also analyzed, and a total of 174 virulence genes belonged to 8 categories were identified. In summary, we studied genomic typing, phylogenetic relationship and virulence gene profiles of S. Derby strains from different sources in China. These findings were beneficial for the epidemiology and pathogenesis of Salmonella.

Biofilm-forming ability of Salmonella enterica strains of different serotypes isolated from multiple sources in China.

Salmonella is an important zoonotic and foodborne pathogen that can infect humans and animals, causing severe concerns about food safety and a heavy financial burden worldwide. The pathogen can adhere to living and abiotic surfaces by forming biofilms, which increases the risk of transmission and infection. In this study, we investigated the biofilm-forming ability of 243 Salmonella strains of 36 serotypes from different sources in China using microplate crystal violet staining method. The results showed that 99.6% tested strains, with the exception of one strain of S. Thompson, were capable of forming biofilms. The strains with the biofilm-forming ability of strong, medium and weak accounted for 2.88%, 24.28% and 72.43%, respectively. The strains of S. Havana and S. Hvittingfoss had the strongest biofilm-forming ability, with the OD570 of 0.81 ± 0.02 and 0.81 ± 0.38, respectively, while the strains of S. Agona and S. Bovismorbificans had the weakest biofilm-forming ability, with the OD570 of 0.16 ± 0.02 and 0.15 ± 0.00, respectively. Furthermore, statistical analysis results demonstrated that isolation of source had no effect on the biofilm formation ability, while the detection rates of pefABCD and ddhC were positively correlated with the biofilm formation ability of Salmonella. In particular, the detection rate of ddhC gene was more than 60% in the biofilm forming strains. These findings have important guiding significance for the investigation of pathogenesis, as well as the prevention and control of salmonellosis.

Decoupling of the anode and cathode ultrasonic responses to the state of charge of a lithium-ion battery.

An ultrasonic method for lithium-ion battery (LIB) state of charge (SoC) estimation is a promising emerging technology which may largely improve the SoC estimation accuracy. Previously, it was unknown whether the SoC change induced ultrasonic signal change originated from the anode or the cathode, because the thicknesses of cathodes, anodes and separators are much smaller than the ultrasonic wavelength, which makes it impossible to decouple the anodic and cathodic influence. To quantitatively solve the above problem, we have designed a special half-cell architecture with an extra-thick separator (675 µm) to study the reflected ultrasonic signal. The thickened separator would significantly delay the reflection of ultrasonic waves from the counter-electrode (Li), so that the influence of the working electrode (LiFePO4 or graphite) on the ultrasonic wave can be studied separately. As a result, in the Gr anode, the time of flight (ToF) of the ultrasonic wave decreases with SoC, the changing rate coefficient of which is in the range of -110 to -70 ps µmGr thickness-1, depending on the compact density. A lower compact density electrode leads to a more significant ultrasonic ToF decrease and intensity increase while in the LFP cathode, the ToF increases with SoC, the changing rate coefficient of which is in the range of 15-43 ps µmLFP thickness-1. The ToF change of the transmitted ultrasound through multilayered LIB matches very well with the sum of the ToF change in each electrode measured with our half-cells.

Bilateral treatment of the masseter with botulinum toxin: Consequences for mastication, muscle force and the mandibular condyle.

BACKGROUND: Clinical use of botulinum neurotoxins (BoNTs) in masticatory muscles is usually bilateral, but most studies on the functional consequences of BoNT treatment have used unilaterally treated animals. OBJECTIVES: To test the hypothesis that bilateral BoNT treatment of the rabbit masseter hampers mastication and to assess its effects on bone density of the mandibular condyles. METHODS: Ten 5-month-old female rabbits received injections of BoNT into both masseter muscles and nine sham animals received saline. Body weight, incisor bite force during masseter tetany, and surface and fine-wire electromyography (EMG) of the masseter and medial pterygoid muscles were assessed at regular intervals. Half the sample was terminated after 4 weeks and the remainder after 12 weeks. Muscles were weighed and mandibular condyles were scanned with microCT to analyse bone density. RESULTS: BoNT rabbits lost weight and required a soft-food diet. Incisor occlusal force plummeted after BoNT injection and remained lower than the shams. The duration of masticatory cycles was increased in the BoNT rabbits for 5 weeks, with most of the increase due to the adductor burst. Masseteric EMG amplitude began to improve at Week 5, but remained low on the working side throughout the experiment. At the 12-week endpoint, masseter muscles were smaller in the BoNT rabbits. Medial pterygoid muscles did not compensate. Condylar bone density was reduced. CONCLUSION: Bilateral treatment of the rabbit masseter by BoNT severely affected chewing performance. Even after a 3-month recovery period, deficits remained in bite force, muscle size and condylar bone density.

Neurovascular coupling dysfunction in high myopia patients: Evidence from a multi-modal magnetic resonance imaging analysis.

BACKGROUND AND PURPOSE: To investigate neurovascular coupling dysfunction in high myopia (HM) patients. MATERIALS AND METHODS: A total of 37 HM patients and 36 healthy controls were included in this study. Degree centrality (DC), regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional ALFF (fALFF) maps were employed to represent neuronal activity. Cerebral blood perfusion was characterized by cerebral blood flow (CBF). The correlation coefficient was calculated to reflect the relationship between neuronal activity and cerebral blood perfusion. Pearson partial correlation analysis was utilized to evaluate the association between HM dysfunction and clinical indicators. RESULTS: HM patients exhibited significant alterations in neurovascular coupling across 37 brain regions compared to healthy controls. The brain regions with marked changes varied among the four neurovascular coupling patterns, including the middle frontal gyrus, superior occipital gyrus, middle occipital gyrus, and fusiform gyrus. Additionally, the superior frontal gyrus orbital part, medial superior frontal gyrus, inferior occipital gyrus, and dorsolateral superior frontal gyrus displayed significant changes in three coupling patterns. In HM patients, the ReHo-CBF changes in the inferior frontal gyrus orbital part were positively correlated with best-corrected visual acuity (BCVA) and refractive diopter changes. Similarly, the ALFF-CBF changes in the inferior frontal gyrus orbital part showed a positive correlation with refractive diopter changes. ReHo-CBF and ALFF-CBF alterations in the paracentral lobule were positively correlated with BCVA and refractive diopter changes. CONCLUSION: Our findings underscore the abnormal alterations in neurovascular coupling across multiple brain regions in HM patients. These results suggest that neurovascular dysfunction in HM patients may be associated with an aberrant visual regulation mechanism.

Development and characteristics of infrared gradient refractive index chalcogenide glasses by hot pressing.

Compared with ordinary uniform lenses, the length and refractive index distribution of gradient refractive index (GRIN) lenses can effectively correct aberration and chromatic aberration. This advantage makes the miniaturization, integration, and lens lightweight possible. Although the visible GRIN lenses based on silicate glass are widely used, the infrared GRIN lenses based on chalcogenide glass are still elusive. This paper introduces a new method for preparing this kind of lens by hot pressing sintering diffusion of chalcogenide glasses. A series of chalcogenide glasses Ge10As22Se68-xSx (x = 4, 7, 10, 14, 24, 28, 34 mol%) with refractive index range from 2.37 to 2.57 (n@8 µm) and similar glass transition temperature (ΔTg < 10℃) were prepared by melt quenching. The relationship between Raman peaks and the refractive index of glasses was studied. Furthermore, the refractive index profile formed by elemental diffusion was characterized by Raman signals. The results show that the diffusion length reaches more than 290 µm, and larger diffusion distances can be achieved by stacking multiple layers. The obtained GRIN glass maintains good transmittance in the whole atmospheric window of 2 ∼ 12 µm.

Praseodymium mid-infrared emission in AlF3-based glass sensitized by ytterbium.

Broadband emission was obtained over 2.6 to 4.1 µm (Pr3+: 1G4→3F4, 3F3) in AlF3-based glass samples doped with different concentrations of praseodymium and 1 mol% ytterbium using a 976 nm laser pump. An efficient energy transfer process from Yb3+: 2F5/2 to Pr3+: 1G4 was analyzed through emission spectra and fluorescence lifetime values. The absorption and emission cross-sections were calculated by Füchtbauer-Ladenburg and McCumber theories and a positive gain can be obtained when P>0.3. To the best of the authors' knowledge, this work represents the first report of broadband mid-infrared emission of Pr3+ in an AlF3-based glass. The results show that praseodymium doped AlF3-based glass sensitized by ytterbium could be a promising candidate for fiber lasers operating in mid-infrared region.

Characteristics and preparation of a polarization beam splitter based on a chalcogenide dual-core photonic crystal fiber.

We reported on a polarization beam splitter based on a novel chalcogenide dual-core photonic crystal fiber. The glass matrix of the optical fiber is Ge10As22Se68. We used computerized numerical control precision drilling methods to manufacture preforms. Then the preform was drawn into an optical fiber with a regular hole structure. The maximum extinction ratio reached -32.76 dB with a 26.27 mm-long optical fiber. Numerical results show that the shortest working length of the designed polarization beam splitter is 636 µm. In addition, the modeling analysis based on the actual structure shows that the theoretical value is consistent with the measured value.

Age-based targeting of biannual azithromycin distribution for child survival in Niger: an adaptive cluster-randomized trial protocol (AVENIR).

BACKGROUND: Biannual distribution of azithromycin to children 1-59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1-11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance. METHODS: AVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1-11: biannual azithromycin to children 1-11 months old with placebo to children 12-59 months old, 2) azithromycin 1-59: biannual azithromycin to children 1-59 months old, or 3) placebo: biannual placebo to children 1-59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1-59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1-59 months old comparing the azithromycin 1-59 and placebo arms, 2) children 1-11 months old comparing the azithromycin 1-11 and placebo arm, and 3) children 12-59 months in the azithromycin 1-11 and azithromycin 1-59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1-59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1-59 months old. DISCUSSION: As high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival. TRIAL REGISTRATION: This trial was registered on January 13, 2020 (clinicaltrials.gov: NCT04224987 ).

Dual-acting antibacterial porous chitosan film embedded with a photosensitizer.

This study proposes to develop a dual-acting antibacterial film of porous chitosan (Cs) embedded with small molecular compound, which possesses photosensitive characteristics with bactericidal efficacy, to promote the accelerated recovery of infectious wounds. The Cs/small molecular compound (Cs-cpd.2) dressing was prepared using the freeze-drying method. Characterization of the synthesized Cs-cpd.2 indicated that it has high porosity and moisture absorption effect, hence enhancing the absorption of wound exudate. Experimental results showed that Cs-cpd.2 dressing has good bactericidal and bacteriostatic effects on Staphylococcus aureus under visible-light irradiation and has antibacterial effect in the dark. It was also found that the small molecular compound does not have cytotoxicity at a dose of 0-5 µM. Furthermore, Cs-cpd.2 that contained small molecular compound with a concentration of 0.3-1 µM has positive effect on both the cell viability rate and cell proliferation rate of human fibroblast CG1639. Cs-cpd.2 can significantly promote cell proliferation when the small molecular compound and the basic fibroblast growth factor bFGF were added together. Therefore, the proposed Cs-cpd.2 dressing is feasible for photodynamic therapy (PDT) and clinical wound dressing applications.