The incidence of breast implant illness (BII) and BII-related explant procedures has not decreased with current surgical and treatment techniques. It is speculated the main underlying cause of BII complications is the result of chronic, sub-clinical infections residing on and around the implant. The infection, and subsequent biofilm, produce antagonistic compounds that drive chronic inflammation and immune responses. In this study, the microbial communities in over 600 consecutive samples of infected explant capsules and tissues were identified via next-generation sequencing to identify any commonality between samples. The majority of the bacteria identified were Gram-positive, with Cutibacterium acnes and Staphylococcus epidermidis being the dominant organisms. No correlation between sample richness and implant filling was found. However, there was a significant correlation between sample richness and patient age. Due to the complex nature, breast augmentation failures may be better addressed from a holistic approach than one of limited scope.

Wound aetiology, host characteristics and the wound microbiome contribute to chronic wound development. Yet, there is little accounting for the relative importance of these factors to predict wound healing. Here, a structural equation model was developed to provide such an explanatory and predictive framework. Chronic wounds from 565 patients treated at a clinic practicing biofilm‐based wound care were included. Patient information included DNA sequencing‐based wound microbiome clinical reports corresponding to the initial clinical visit. Wound microbiome data was integrated into the SEM as a latent variable using a pre‐modelling parcel optimization routine presented herein for the first time (available as R library parcelR). A microbiome latent construct associated with improved healing was validated, and the final SEM included this latent construct plus three species associated with diminished healing (Anaerococcus vaginalis, Finegoldia magna and Pseudomonas aeruginosa), as well as smoking, wound volume, slough, exudate, edema, percent granulation and wound etiology. This model explained 46% of variations in healing time, with the microbiome contributing the largest proportion of variance explained. Model validity was confirmed with an independent cohort (n = 79) through which ~60% of the variation in healing time was predicted. This model can serve as a foundation for the development of a predictive tool that may have clinical utility.

Persistence - characterized by the transient ability of subpopulations of drug-susceptible parasites to survive exposure to drug - is a major driver of treatment failure and clinical relapses in leishmaniasis. Persisters are characterized by non-dividing or slow-growing state and increased drug tolerance. However, the molecular mechanisms governing formation of persisters remain poorly understood in Leishmania parasites. Here, we developed a model to explore persistence in Leishmania mexicana . Viable promastigote persister-like subpopulations were enriched using Ficoll density gradient centrifugation following lethal exposure to antimonial drugs that killed 80% of parasites. The surviving parasites exhibited delayed growth in drug-free medium that is characteristic for persisters, and significantly higher tolerance to drug upon rechallenge. Transcriptomic profiling across acute stress, drug-free recovery, and rechallenge phases revealed a global remodeling in persisters under all tested conditions. Induction phase in Leishmania persisters was characterized by downregulation of several biological processes and a robust upregulation of nucleolar pathways, supporting epitranscriptomic changes during formation of persisters. Upon drug removal, this profile rapidly reverted, initiating ribosomal biogenesis to exit latency and resume cellular proliferation. Resuscitation phase exhibited activated protein synthesis and upregulation in many biological processes associated with metabolic and mitochondrial functions. Furthermore, comparative analysis of drug responses in rechallenged drug-tolerant persisters and parental parasites exposed to the drug for the first time, revealed that persisters exhibit distinct drug response profiles compared to parental parasites by rapidly implementing a highly conserved, coordinated survival reprogramming, where 316 genes were uniquely downregulated, and 241 genes were upregulated. The distinct features of the drug response in rechallenged persister cells were characterized by the downregulation of mitochondrial function and protein synthesis machinery to induce a dormant, idling state, and the upregulation of drug-response and stress-tolerance genes to survive immediate toxicity. In contrast, parental parasites displayed a broad and disorganized drug response. Additionally, rechallenged persisters exhibited a distinct transcriptomic memory that transiently phenocopies stable genetic resistance. This pre-adapted state is characterized by the targeted upregulation of epigenetic modulators, heavy metal transporters, and catabolic enzymes to maintain viability. These findings demonstrate that drug persistence in Leishmania is not merely a metabolic collapse, but rather a sophisticated survival strategy involving active transcriptome remodeling, downregulation of translation and epigenetic adaptations. This transient state constitutes an initial evolutionary step toward permanent drug resistance and highlights new molecular vulnerabilities for therapeutic interventions aimed at preventing clinical relapse. Author summary: The efficacy of leishmaniasis chemotherapy is often fails because Leishmania parasites survive the drugs by entering a dormant state, causing relapses in patients. In this study, however, we discovered that these parasites are not simply ‘quiescent’. On the contrary, they orchestrate a highly active survival response: they shut down energy-consuming functions while keeping their cellular alert mechanisms active. Remarkably, upon re-exposure to antileishmanial drugs, the parasites recall previous stress events and transiently activate defensive pathways characteristic of stable drug resistance. Understanding how Leishmania employs this temporary adaptive strategy provides critical targets for developing therapies designed to eradicate the infection and avert relapses.

Introduction: Space travel exposes crew to substantial stressors, which may potentially alter their microbiome and be detrimental to their health and safety. We hypothesize that urinary microbiota is altered during a short-duration spaceflight to the International Space Station (ISS). Methods: Urine samples were collected from 4 male crew members. One crew member provided samples while on orbit on the ISS using a urine collection kit (UCK) designed for low-gravity environments. This crew member also provided paired mid-stream and UCK samples on Earth prelaunch and on return for direct comparison of collection methods. Three additional crew members provided mid-stream samples prelaunch and on return, and also for follow-up timepoints to serve as ex post facto control samples. Urine was stored at −80℃ and sent for 16s next-generation sequencing (MicroGenDX, Lubbock, TX). Results: Bacterial load ( P = .52), species richness ( P = .64), and differences in microbiota composition ( P = .26) did not significantly vary by the collection method (mid-stream vs UCK). Significant differences in species richness, load, and microbial composition among preflight, orbital, and return mission samples were detected ( P = .047, F = 1.8092, df = 2.9, R2 = 0.34076). Orbital microbial composition significantly differed from preflight ( P = .03) and return ( P = .03), whereas preflight and return samples did not differ ( P > .05). Comparison with the limited follow-up ex post facto Earth-bound samples serving as controls showed no significant differences among preflight or return mission samples, but preflight ( P = .04) and return ( P = .05) did significantly differ compositionally from orbital samples. Continuous temporal effects on composition were evaluated through which bacterial load ( P = .05) was statistically significant, peaking during the orbital period. Conclusions: Results are consistent with an effect of space travel altering the urinary microbiota. Further studies are needed to confirm this result and to better understand whether such changes may be detrimental to the health and safety of space travelers and professional astronauts.

Wound etiology, host characteristics, and the wound microbiome contribute to chronic wound development. Yet, there is little accounting for the relative importance of these factors to predict wound healing. Here, a structural equation model was developed to provide such an explanatory and predictive framework. Chronic wounds from 565 patients treated at a clinic practicing biofilm-based wound care were included. Patient information included DNA sequencing-based wound microbiome clinical reports corresponding to initial clinical visit. Wound microbiome data was integrated into the SEM as a latent variable using a pre-modeling parcel optimization routine presented herein for the first time (available as R library parcelR ). A microbiome latent construct associated with improved healing was validated, and the final SEM included this latent construct plus three species associated with diminished healing ( Anaerococcus vaginalis, Finegoldia magna, Pseudomonas aeruginosa ), as well as smoking, wound volume, slough, exudate, edema, percent granulation, and wound etiology This model explained 46% of variation in healing time with the microbiome contributing the largest proportion of variance explained. Model validity was confirmed with an independent cohort (n = 79) through which ∼60% of variation in healing time was predicted. This model can serve as foundation for development of a predictive tool that may have clinical utility.

Severe equine asthma (SEA) is a chronic inflammation of airways affecting ~14–20% of adult horses in the Northern Hemisphere. SEA is characterized by a mixed phenotype of T helper cell responses with marked neutrophilia in the bronchoalveolar lavage fluid (BALF) of affected horses. Human studies have demonstrated the impact of gut microbiota in many diseases, including asthma susceptibility and severity. However, the potential role of the gut–lung axis in the development and persistence of SEA remains to be determined. This study aimed to identify key bacterial, archaeal, and fungal microbiota alterations in the feces of horses with severe neutrophilic asthma (n = 4) compared to healthy horses (n = 8). Archaea alpha diversity was lower in the feces of SEA-affected horses, but with high abundance of archaea genus Candidatus Nitrosocosmicus, which impacts hydrogen metabolism in horses with SEA. Other key bacterial and fungi species differences lower in SEA included Blautia and Alternaria, respectively. Blautia is associated with positive metabolic health due to its fibrolytic capabilities. Overall, our findings indicate that horses experiencing severe neutrophilic asthma have an imbalance in the intestinal microbiota that may exacerbate systemic inflammatory responses through the gut–lung axis.