Ceftriaxone Administration Disrupts Intestinal Homeostasis, Mediating Noninflammatory Proliferation and Dissemination of Commensal Enterococci

ABSTRACTEnterococci are Gram-positive commensals of the mammalian intestinal tract and harbor intrinsic resistance to broad-spectrum cephalosporins. Disruption of colonization resistance in humans by antibiotics allows enterococci to proliferate in the gut and cause disseminated infections. In this study, we usedEnterococcus faecalis(EF)-colonized mice to study the dynamics of enterococci, commensal microbiota, and the host in response to systemic ceftriaxone administration. We found that the mouse model recapitulates intestinal proliferation and dissemination of enterococci seen in humans. Employing a ceftriaxone-sensitive strain of enterococci (E. faecalisJL308), we showed that increased intestinal abundance is critical for the systemic dissemination of enterococci. Investigation of the impact of ceftriaxone on the mucosal barrier defenses and integrity suggested that translocation of enterococci across the intestinal mucosa was not associated with intestinal pathology or increased permeability. Ceftriaxone-induced alteration of intestinal microbial composition was associated with transient increase in the abundance of multiple bacterial operational taxonomic units (OTUs) in addition to enterococci, for example, lactobacilli, which also disseminated to the extraintestinal organs. Collectively, these results emphasize that ceftriaxone-induced disruption of colonization resistance and alteration of mucosal homeostasis facilitate increased intestinal abundance of a limited number of commensals along with enterococci, allowing their translocation and systemic dissemination in a healthy host.

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Multi-Body-Site Microbiome and Culture Profiling of Military Trainees Suffering from Skin and Soft Tissue Infections at Fort Benning, Georgia

mSphere ◽

10.1128/msphere.00232-16 ◽

2016 ◽

Vol 1 (5) ◽

Cited By ~ 10

Author(s):

Jatinder Singh ◽

Ryan C. Johnson ◽

Carey D. Schlett ◽

Emad M. Elassal ◽

Katrina B. Crawford ◽

...

Keyword(s):

High Throughput ◽

High Throughput Sequencing ◽

Bacterial Community Composition ◽

Soft Tissue Infections ◽

Microbial Composition ◽

Content Type ◽

Microbial Dysbiosis ◽

Lack Of Information ◽

The Impact ◽

Nasal Microbiota

ABSTRACT While it is evident that nasal colonization with S. aureus increases the likelihood of SSTI, there is a significant lack of information regarding the contribution of extranasal colonization to the overall risk of a subsequent SSTI. Furthermore, the impact of S. aureus colonization on bacterial community composition outside the nasal microbiota is unclear. Thus, this report represents the first investigation that utilized both culture and high-throughput sequencing techniques to analyze microbial dysbiosis at multiple body sites of healthy and diseased/colonized individuals. The results described here may be useful in the design of future methodologies to treat and prevent SSTIs. Skin and soft tissue infections (SSTIs) are common in the general population, with increased prevalence among military trainees. Previous research has revealed numerous nasal microbial signatures that correlate with SSTI development and Staphylococcus aureus colonization. Thus, we hypothesized that the ecology of the inguinal, oropharynx, and perianal regions may also be altered in response to SSTI and/or S. aureus colonization. We collected body site samples from 46 military trainees with purulent abscess (SSTI group) as well as from 66 asymptomatic controls (non-SSTI group). We also collected abscess cavity samples to assess the microbial composition of these infections. Samples were analyzed by culture, and the microbial communities were characterized by high-throughput sequencing. We found that the nasal, inguinal, and perianal regions were similar in microbial composition and significantly differed from the oropharynx. We also observed differences in Anaerococcus and Streptococcus abundance between the SSTI and non-SSTI groups for the nasal and oropharyngeal regions, respectively. Furthermore, we detected community membership differences between the SSTI and non-SSTI groups for the nasal and inguinal sites. Compared to that of the other regions, the microbial compositions of the nares of S. aureus carriers and noncarriers were dramatically different; we noted an inverse correlation between the presence of Corynebacterium and the presence of Staphylococcus in the nares. This correlation was also observed for the inguinal region. Culture analysis revealed elevated methicillin-resistant S. aureus (MRSA) colonization levels for the SSTI group in the nasal and inguinal body sites. Together, these data suggest significant microbial variability in patients with SSTI as well as between S. aureus carriers and noncarriers. IMPORTANCE While it is evident that nasal colonization with S. aureus increases the likelihood of SSTI, there is a significant lack of information regarding the contribution of extranasal colonization to the overall risk of a subsequent SSTI. Furthermore, the impact of S. aureus colonization on bacterial community composition outside the nasal microbiota is unclear. Thus, this report represents the first investigation that utilized both culture and high-throughput sequencing techniques to analyze microbial dysbiosis at multiple body sites of healthy and diseased/colonized individuals. The results described here may be useful in the design of future methodologies to treat and prevent SSTIs.

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Response of Germfree Mice to Colonization by Oxalobacter formigenes and Altered Schaedler Flora

Applied and Environmental Microbiology ◽

10.1128/aem.02381-16 ◽

2016 ◽

Vol 82 (23) ◽

pp. 6952-6960 ◽

Cited By ~ 8

Author(s):

Xingsheng Li ◽

Melissa L. Ellis ◽

Alexander E. Dowell ◽

Ranjit Kumar ◽

Casey D. Morrow ◽

...

Keyword(s):

Calcium Oxalate ◽

Mouse Models ◽

Stone Formation ◽

Proximal Colon ◽

Urinary Calcium ◽

Free Calcium ◽

Oxalobacter Formigenes ◽

Microbial Composition ◽

Content Type ◽

The Impact

ABSTRACTColonization withOxalobacter formigenesmay reduce the risk of calcium oxalate kidney stone disease. To improve our limited understanding of host-O. formigenesand microbe-O. formigenesinteractions, germfree mice and mice with altered Schaedler flora (ASF) were colonized withO. formigenes. Germfree mice were stably colonized withO. formigenes, which suggests thatO. formigenesdoes not require other organisms to sustain its survival. Examination of intestinal material indicated no viableO. formigenesin the small intestine and ∼4 × 106CFUO. formigenesper 100 mg contents in the cecum and proximal colon, with ∼0.02% of total cecalO. formigenescells being tightly associated with the mucosa.O. formigenesdid not alter the overall microbial composition of ASF, and ASF did not affect the capacity ofO. formigenesto degrade dietary oxalate in the cecum. Twenty-four-hour collections of urine and feces in metabolic cages in semirigid isolators demonstrated that the introduction of ASF into germfree mice significantly reduced urinary oxalate excretion. These experiments also showed thatO. formigenes-monocolonized mice excreted significantly more urinary calcium than did germfree mice, which may be due to degradation of calcium oxalate crystals byO. formigenesand subsequent intestinal absorption of free calcium. In conclusion, the successful establishment of mouse models with defined flora andO. formigenesshould improve our understanding ofO. formigenes-host andO. formigenes-microbe interactions. These data support the use ofO. formigenesas a probiotic that has limited impact on the composition of the resident microbiota but provides an efficient oxalate-degrading function.IMPORTANCEDespite evidence suggesting that a lack ofOxalobacter formigenescolonization is a risk factor for calcium oxalate stone formation, little is known aboutO. formigenesbiology. This study is the first to utilize germfree mice to examine the response to monocolonization withO. formigenes, as well as the impact of a defined bacterial cocktail (i.e., ASF) onO. formigenescolonization. This study demonstrated that germfree mice receiving their regular diet remained monocolonized withO. formigenes, and it suggests that further studies withO. formigenesgnotobiotic mouse models could improve our understanding ofO. formigenesbiology and host-O. formigenesand microbe-O. formigenesinteractions.

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Oral DAV131, a Charcoal-Based Adsorbent, Inhibits Intestinal Colonization by β-Lactam-Resistant Klebsiella pneumoniae in Cefotaxime-Treated Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00039-13 ◽

2013 ◽

Vol 57 (11) ◽

pp. 5423-5425 ◽

Cited By ~ 10

Author(s):

Nathalie Grall ◽

Laurent Massias ◽

Thu Thuy Nguyen ◽

Sakina Sayah-Jeanne ◽

Nicolas Ducrot ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Intestinal Tract ◽

Area Under The Curve ◽

Resistant Bacteria ◽

Intestinal Colonization ◽

Colonization Resistance ◽

Content Type ◽

Resistant Strains ◽

The Impact ◽

Indigenous Microflora

ABSTRACTAntibiotics excreted into the intestinal tract, such as broad-spectrum cephalosporins, disrupt the indigenous microflora, affect colonization resistance (CR), and promote intestinal colonization by resistant bacteria. We tested whether oral DAV131, a charcoal-based adsorbent, would prevent colonization by a cefotaxime (CTX)-resistantKlebsiella pneumoniaestrain (PUG-2) in CTX-treated mice. Mice received CTX, saline, CTX and DAV131, or saline and DAV131 for 3 days before oral challenge with 106CFU of PUG-2. The fecal CTX concentrations and counts of PUG-2 were assayed. Fecal CTX disappeared when DAV131 was given concomitantly with CTX (P< 0.05), and the area under the curve of PUG-2 fecal density was significantly reduced (P< 0.01). In conclusion, reducing intestinal antibiotic exposure with DAV131 may reduce colonization by resistant strains during treatment compared to treatment with CTX only. This might open new possibilities for decreasing the impact of antibiotics on the intestinal microbiota during treatments.

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The Impact of Anthelmintic Treatment on Human Gut Microbiota Based on Cross-Sectional and Pre- and Postdeworming Comparisons in Western Kenya

mBio ◽

10.1128/mbio.00519-19 ◽

2019 ◽

Vol 10 (2) ◽

Cited By ~ 10

Author(s):

Alice V. Easton ◽

Mariam Quiñones ◽

Ivan Vujkovic-Cvijin ◽

Rita G. Oliveira ◽

Stella Kepha ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Intestinal Parasites ◽

Fold Change ◽

Rrna Gene ◽

Human Gut ◽

Microbial Composition ◽

Content Type ◽

Average Fold Change ◽

The Impact

ABSTRACT Murine studies suggest that the presence of some species of intestinal helminths is associated with changes in host microbiota composition and diversity. However, studies in humans have produced varied conclusions, and the impact appears to vary widely depending on the helminth species present. To demonstrate how molecular approaches to the human gut microbiome can provide insights into the complex interplay among disparate organisms, DNA was extracted from cryopreserved stools collected from residents of 5 rural Kenyan villages prior to and 3 weeks and 3 months following albendazole (ALB) therapy. Samples were analyzed by quantitative PCR (qPCR) for the presence of 8 species of intestinal parasites and by MiSeq 16S rRNA gene sequencing. Based on pretreatment results, the presence of neither Ascaris lumbricoides nor Necator americanus infection significantly altered the overall diversity of the microbiota in comparison with age-matched controls. Following ALB therapy and clearance of soil-transmitted helminths (STH), there were significant increases in the proportion of the microbiota made up by Clostridiales (P = 0.0002; average fold change, 0.57) and reductions in the proportion made up by Enterobacteriales (P = 0.0004; average fold change, −0.58). There was a significant posttreatment decrease in Chao1 richness, even among individuals who were uninfected pretreatment, suggesting that antimicrobial effects must be considered in any posttreatment setting. Nevertheless, the helminth-associated changes in Clostridiales and Enterobacteriales suggest that clearance of STH, and of N. americanus in particular, alters the gut microbiota. IMPORTANCE The gut microbiome is an important factor in human health. It is affected by what we eat, what medicines we take, and what infections we acquire. In turn, it affects the way we absorb nutrients and whether we have excessive intestinal inflammation. Intestinal worms may have an important impact on the composition of the gut microbiome. Without a complete understanding of the impact of mass deworming programs on the microbiome, it is impossible to accurately calculate the cost-effectiveness of such public health interventions and to guard against any possible deleterious side effects. Our research examines this question in a “real-world” setting, using a longitudinal cohort, in which individuals with and without worm infections are treated with deworming medication and followed up at both three weeks and three months posttreatment. We quantify the impact of roundworms and hookworms on gut microbial composition, suggesting that the impact is small, but that treatment of hookworm infection results in significant changes. This work points to the need for follow-up studies to further examine the impact of hookworm on the gut microbiota and determine the health consequences of the observed changes.

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Impact of Antibiotic-Resistant Bacteria on Immune Activation and Clostridioides difficile Infection in the Mouse Intestine

Infection and Immunity ◽

10.1128/iai.00362-19 ◽

2020 ◽

Vol 88 (4) ◽

Cited By ~ 1

Author(s):

James W. Keith ◽

Qiwen Dong ◽

Matthew T. Sorbara ◽

Simone Becattini ◽

Jonathan K. Sia ◽

...

Keyword(s):

Colonic Mucosa ◽

Bacterial Species ◽

Intestinal Lumen ◽

Resistant Bacteria ◽

Colonization Resistance ◽

Antibiotic Resistant ◽

Content Type ◽

Clostridioides Difficile ◽

Wide Range ◽

The Impact

ABSTRACT Antibiotic treatment of patients undergoing complex medical treatments can deplete commensal bacterial strains from the intestinal microbiota, thereby reducing colonization resistance against a wide range of antibiotic-resistant pathogens. Loss of colonization resistance can lead to marked expansion of vancomycin-resistant Enterococcus faecium (VRE), Klebsiella pneumoniae, and Escherichia coli in the intestinal lumen, predisposing patients to bloodstream invasion and sepsis. The impact of intestinal domination by these antibiotic-resistant pathogens on mucosal immune defenses and epithelial and mucin-mediated barrier integrity is unclear. We used a mouse model to study the impact of intestinal domination by antibiotic-resistant bacterial species and strains on the colonic mucosa. Intestinal colonization with K. pneumoniae, Proteus mirabilis, or Enterobacter cloacae promoted greater recruitment of neutrophils to the colonic mucosa. To test the hypothesis that the residual microbiota influences the severity of colitis caused by infection with Clostridioides difficile, we coinfected mice that were colonized with ampicillin-resistant bacteria with a virulent strain of C. difficile and monitored colonization and pathogenesis. Despite the compositional differences in the gut microbiota, the severity of C. difficile infection (CDI) and mortality did not differ significantly between mice colonized with different ampicillin-resistant bacterial species. Our results suggest that the virulence mechanisms enabling CDI and epithelial destruction outweigh the relatively minor impact of less-virulent antibiotic-resistant intestinal bacteria on the outcome of CDI.

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Depletion of Alveolar Macrophages Increases Pulmonary Neutrophil Infiltration, Tissue Damage, and Sepsis in a Murine Model of Acinetobacter baumannii Pneumonia

Infection and Immunity ◽

10.1128/iai.00128-20 ◽

2020 ◽

Vol 88 (7) ◽

Author(s):

Hiu Ham Lee ◽

Lilit Aslanyan ◽

Arjun Vidyasagar ◽

Melissa B. Brennan ◽

Maxine S. Tauber ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Alveolar Macrophages ◽

Tissue Damage ◽

Bacterial Pathogen ◽

Neutrophil Infiltration ◽

Pulmonary Tissue ◽

Content Type ◽

Systemic Dissemination ◽

The Impact

ABSTRACT Acinetobacter baumannii has emerged as an important etiological agent of hospital-related infections, especially nosocomial pneumonia. The virulence factors of this bacterium and their interactions with the cells and molecules of the immune system just recently began to be extensively studied. Here, we investigated the impact of alveolar macrophages on A. baumannii pneumonia using a mouse model of infection and a flexible tissue culture system. We hypothesized that depletion of macrophages would enhance sepsis and severity of A. baumannii disease. We showed that macrophages are important for modulating the antibacterial function of neutrophils and play an important role in eradicating A. baumannii infection in vivo. Our findings suggest that in the absence of macrophages in the lungs, A. baumannii replicates significantly, and host proinflammatory cytokines are considerably reduced. Neutrophils are abundantly recruited to pulmonary tissue, releasing high amounts of reactive oxygen species and causing extensive tissue damage. The ability of A. baumannii to form biofilms and resist oxidative stress in the respiratory tract facilitates systemic dissemination and ultimately death of infected C57BL/6 mice. These results provide novel information regarding A. baumannii pathogenesis and may be important for the development of therapies aimed at reducing morbidity and mortality associated with this emerging bacterial pathogen.

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Tapering Courses of Oral Vancomycin Induce Persistent Disruption of the Microbiota That Provide Colonization Resistance to Clostridium difficile and Vancomycin-Resistant Enterococci in Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02237-17 ◽

2018 ◽

Vol 62 (5) ◽

Cited By ~ 9

Author(s):

Myreen E. Tomas ◽

Thriveen S. C. Mana ◽

Brigid M. Wilson ◽

Michelle M. Nerandzic ◽

Samira Joussef-Piña ◽

...

Keyword(s):

Clostridium Difficile ◽

Anaerobic Bacteria ◽

Multiple Time ◽

Colonization Resistance ◽

Content Type ◽

Vancomycin Resistant Enterococci ◽

Indigenous Microbiota ◽

Vancomycin Resistant ◽

Multiple Time Points ◽

The Impact

ABSTRACT Vancomycin taper regimens are commonly used for the treatment of recurrent Clostridium difficile infections. One rationale for tapering and pulsing of the dose at the end of therapy is to reduce the selective pressure of vancomycin on the indigenous intestinal microbiota. Here, we used a mouse model to test the hypothesis that the indigenous microbiota that provide colonization resistance against C. difficile and vancomycin-resistant enterococci (VRE) is repopulated during tapering courses of vancomycin. Mice were treated orally with vancomycin daily for 10 days, vancomycin in a tapering dose for 42 days, fidaxomicin for 10 days, or saline. To assess colonization resistance, subsets of mice were challenged with 10 4 CFU of C. difficile or VRE at multiple time points during and after completion of treatment. The impact of the treatments on the microbiome was measured by cultures, real-time PCR for selected anaerobic bacteria, and deep sequencing. Vancomycin taper-treated mice developed alterations of the microbiota and disruption of colonization resistance that was persistent 18 days after treatment. In contrast, mice treated with a 10-day course of vancomycin exhibited recovery of the microbiota and of colonization resistance by 15 days after treatment, and fidaxomicin-treated mice maintained intact colonization resistance. These findings demonstrate that alteration of the indigenous microbiota responsible for colonization resistance to C. difficile and VRE persist during and after completion of tapering courses of vancomycin.

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Species Deletions from Microbiome Consortia Reveal Key Metabolic Interactions between Gut Microbes

mSystems ◽

10.1128/msystems.00185-19 ◽

2019 ◽

Vol 4 (4) ◽

Cited By ~ 16

Author(s):

Natalia Gutiérrez ◽

Daniel Garrido

Keyword(s):

Gut Microbiome ◽

Keystone Species ◽

Microbial Interactions ◽

Microbial Consortia ◽

Microbial Composition ◽

Bifidobacterium Adolescentis ◽

Fermentation Products ◽

Content Type ◽

Gut Microbes ◽

The Impact

ABSTRACT The gut microbiome is a complex microbial community that plays a key role in human health. Diet is an important factor dictating gut microbiome composition. This is mediated by multiple microbe-microbe interactions that result in the fermentation of nondigestible carbohydrates and the production of short-chain fatty acids. Certain species play key metabolic roles in the microbiome, and their disappearance could result in dysbiosis. In this work, a synthetic consortium of 14 gut microbes was studied during the utilization of prebiotic inulin in batch bioreactors. Fermentations were repeated leaving one species out every time, in order to evaluate the impact of their elimination on the system. Substrate consumption, microbial composition, and metabolite production were determined. Single deletions never resulted in a complete loss of bacterial growth or inulin consumption, suggesting functional redundancy. Deletions of Bacteroides dorei and Lachnoclostridium clostridioforme resulted in lower biomass and higher residual inulin. The absence of B. dorei impacted the abundance of the other 10 species negatively. Lachnoclostridium symbiosum, a butyrate producer, appeared to be the most sensitive species to deletions, being stimulated by the presence of Escherichia coli, Bifidobacterium adolescentis, B. dorei, and Lactobacillus plantarum. Conversely, bioreactors without these species did not show butyrate production. L. clostridioforme was observed to be essential for propionate production, and B. dorei for lactate production. Our analysis identified specific members that were essential for the function of the consortium. In conclusion, species deletions from microbial consortia could be a useful approach to identify relevant interactions between microorganisms and defining metabolic roles in the gut microbiome. IMPORTANCE Gut microbes associate, compete for, and specialize in specific metabolic tasks. These interactions are dictated by the cross-feeding of degradation or fermentation products. However, the individual contribution of microbes to the function of the gut microbiome is difficult to evaluate. It is essential to understand the complexity of microbial interactions and how the presence or absence of specific microorganisms affects the stability and functioning of the gut microbiome. The experimental approach of this study could be used for identifying keystone species, in addition to redundant functions and conditions that contribute to community stability. Redundancy is an important feature of the microbiome, and its reduction could be useful for the design of microbial consortia with desired metabolic properties enhancing the tasks of the keystone species.

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The More Control, the Better?

Journal of Media Psychology Theories Methods and Applications ◽

10.1027/1864-1105/a000114 ◽

2014 ◽

Vol 26 (2) ◽

pp. 81-91 ◽

Cited By ~ 2

Author(s):

Jeeyun Oh ◽

Mun-Young Chung ◽

Sangyong Han

Keyword(s):

Mixed Design ◽

Negative Effects ◽

Story Structure ◽

Content Type ◽

High User ◽

User Control ◽

Rigorous Research ◽

Control Versus ◽

The Media ◽

The Impact

Despite of the popularity of interactive movie trailers, rigorous research on one of the most apparent features of these interfaces – the level of user control – has been scarce. This study explored the effects of user control on users’ immersion and enjoyment of the movie trailers, moderated by the content type. We conducted a 2 (high user control versus low user control) × 2 (drama film trailer versus documentary film trailer) mixed-design factorial experiment. The results showed that the level of user control over movie trailer interfaces decreased users’ immersion when the trailer had an element of traditional story structure, such as a drama film trailer. Participants in the high user control condition answered that they were less fascinated with, absorbed in, focused on, mentally involved with, and emotionally affected by the movie trailer than participants in the low user control condition only with the drama movie trailer. The negative effects of user control on the level of immersion for the drama trailer translated into users’ enjoyment. The impact of user control over interfaces on immersion and enjoyment varies depending on the nature of the media content, which suggests a possible trade-off between the level of user control and entertainment outcomes.

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Perceived workplace gender-bias and psychological impact

European Journal of Training and Development ◽

10.1108/ejtd-09-2018-0088 ◽

2019 ◽

Vol 43 (3/4) ◽

pp. 339-353 ◽

Cited By ~ 2

Author(s):

Siham Lekchiri ◽

Cindy Crowder ◽

Anna Schnerre ◽

Barbara A.W. Eversole

Keyword(s):

Gender Bias ◽

Critical Incident ◽

Psychological Impact ◽

Working Women ◽

Content Type ◽

Treatment Bias ◽

Male Dominated ◽

The Impact ◽

Organizational Mechanisms ◽

Practical Implications

Purpose The purpose of this paper is to explore the experiences of working women in a male-dominated country (Morocco) and unveil the unique challenges and everyday gender-bias they face, the psychological impact of the perceived gender-bias and, finally, identify a variety of coping strategies or combatting mechanisms affecting their motivation and retention in the workplace. Design/methodology/approach Empirical evidence was obtained using a qualitative research method. The Critical Incident Technique (CIT) was used to collect incidents recalled by women in the select institution reflecting their perceptions of their managers’ ineffective behaviors towards them and the impact of these behaviors. The critical incidents were inductively coded, and behavioral statements were derived from the coded data. Findings The qualitative data analysis led them to structure the data according to two theme clusters: The perceived gender-bias behaviors (Covert and evident personal and organizational behaviors) and Psychological impacts resulting from the perceived bias. These behavioral practices included abusive behaviors, unfair treatment, bias and lack of recognition. The psychological impact elements involved decreased productivity, depression, anxiety and low self-esteem. Practical implications Understanding these experiences can facilitate the identification of strategies geared towards the retention of women in the workforce, and Moroccan organizations can develop and implement strategies and policies that are geared towards eliminating gender-bias in the workplace and to retaining and motivating women who remain ambitious to work in male-dominated environments and cultures. Originality/value This paper provides evidence that sufficient organizational mechanisms to support women in male-dominated environments are still unavailable, leaving them to find the proper coping mechanisms to persevere and resist.

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