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Acinetobacter baumannii has emerged as a multidrug-resistant (MDR) superbug by causing severe infections, with high mortality rates. The ability of A. baumannii to form biofilms significantly contributes to its persistence in diverse environmental and hospital settings. Here we report that farnesol, an FDA-approved commercial cosmetic and flavoring agent, demonstrates efficacy for both inhibition of biofilm formation, and disruption of established A. baumannii biofilms. Moreover, no resistance to farnesol was observed even after prolonged culture in the presence of sub-inhibitory farnesol doses. Farnesol combats A. baumannii biofilms by direct killing, while also facilitating biofilm detachment. Furthermore, farnesol was safe, and effective, for both prevention and treatment of A. baumannii biofilms in an ex vivo burned human skin model. Since current treatment options for A. baumannii biofilm infections were mainly counted on the combination therapy of last-resort antibiotics, and clearly non-sustainable due to robust MDR phenotype of A. baumannii, we propose that farnesol alone can be repurposed as a highly effective agent for both preventing and treating life-threating biofilm-associated infections of A. baumannii due to its proven safety, convenient topical delivery, and excellent efficiency, plus its superiority of evading resistance development.

The family of ESKAPE pathogens is comprised of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter. Together they are the main contributors of nosocomial infections and are well established for their ability to “escape” antibiotics. Farnesol is an FDA-approved cosmetic and flavoring agent with significant anti-biofilm properties. In a proprietary emulsion, farnesol has been shown to be capable of disrupting S. aureus, P. aeruginosa, and A. baumannii biofilms. The current work demonstrates that this farnesol emulsion reduces the number of viable bacteria, while also leading to reductions in biomass, of the other three ESKAPE pathogens: Enterococcus faecium, Klebsiella pneumoniae, and Enterobacter, both in vitro and in an ex vivo human skin model. A concentration of 0.5 mg/mL was effective for impeding biofilm development of all three bacteria, while 1 mg/mL for E. faecium and K. pneumoniae, or 0.2 mg/mL for E. cloacae, was able to kill bacteria in established biofilms. Contrary to antibiotics, no resistance to farnesol was observed for E. faecium or K. pneumoniae. The results indicate that farnesol is effective for direct cell killing and also has the ability to induce biofilm detachment from surfaces, as confirmed using Live/Dead image analysis. Our findings confirm that farnesol emulsion is an effective broad-spectrum agent to impede ESKAPE biofilms.

Biofilm-associated infections caused by drug-resistant and persistent bacteria remain a significant clinical challenge. Here we report that farnesol, commercially available as a cosmetic and flavoring agent, shows significant anti-biofilm properties when dissolved in ethanol using a proprietary formulation emulsion technique. Farnesol in the new formulation inhibits biofilm formation and disrupts established biofilms for Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, including their polymicrobial biofilms, and, moreover, kills S. aureus persister cells that have developed tolerance to antibiotics. No resistance to farnesol was observed for S. aureus after twenty continuous passages. Farnesol combats biofilms by direct killing, while also facilitating biofilm detachment. Furthermore, farnesol was safe and effective for preventing and treating biofilm-associated infections of both types of bacteria in an ex vivo burned human skin model. These data suggest that farnesol in the new formulation is an effective broad-spectrum anti-biofilm agent with promising clinical potential. Due to its established safety, low-cost, versatility, and excellent efficacy—including ability to reduce persistent and resistant microbial populations—farnesol in the proprietary formulation represents a compelling transformative, translational, and commercial platform for addressing many unsolved clinical challenges.

Eighty percent of bacterial infections associated with living tissue and medical devices are linked to drug-resistant biofilms, leading to lengthy and costly recoveries. Laser-induced hyperthermia can disrupt cell proliferation within biofilms and increase susceptibility to antibiotics. However, there can be bacterial survival differences dependent upon laser irradiation times, and prolonged time at elevated temperature can damage healthy tissue. The objective of this study was to use survival analysis to model the impact of temperature increases on reducing viable biofilm bacteria. In vitro biofilms of Escherichia coli were grown on silicone discs or silicone doped with photothermal poly(3,4-ethylenedioxythiophene) hydrate (PEDOT) nanotubes, and subjected to laser-induced hyperthermia, using a 3 W continuous wave laser at 800 nm for varying times. The number of colony forming units per milliliter (CFU/mL) and maximum temperature were measured after each trial. Survival analysis was employed to estimate bacterial cell proliferation post-treatment to provide a quantitative framework for future studies evaluating photothermal inactivation of bacterial biofilms. The results demonstrate the first application of survival analysis for predicting the likelihood of bacterial cell proliferation based on temperature.

Breast cancer can harbor intracellular bacteria, which may have an impact on metastasis and therapeutic responses. Silver nanoparticles are FDA-approved for their antimicrobial potential, plus they have pleiotropic benefits for eradicating cancer cells. In the current work we synthesized photothermal silver nanoparticles (AgNPs) with an absorption at 800 nm for heat generation when exposed to near-infrared laser irradiation. Breast cell lines MCF 10A, MCF7, and MDA MB 231 were infected with Pseudomonas aeruginosa, and their response to AgNPs, heat, or photothermal therapy (PTT) was evaluated. The results demonstrate that the application of a brief heating of cells treated with AgNPs offers a synergistic benefit in killing both infected and non-infected cells. Using 10 µg/mL of AgNPs plus laser stimulation induced a temperature change of 12 °C, which was sufficient for reducing non-infected breast cells by 81–94%. Infected breast cells were resistant to PTT, with only a reduction of 45–68%. In the absence of laser stimulation, 10 µg/mL of AgNPs reduced breast cell populations by 10–65% with 24 h of exposure. This concentration had no impact on the survival of planktonic bacteria with or without laser stimulation, although infected breast cells had a 42–90% reduction in intracellular bacteria. Overall, this work highlights the advantages of AgNPs for the generation of heat, and to augment the benefits of heat, in breast cancer cells harboring intracellular infection.

Objective To determine whether photothermal polymer nanoparticles (NPs) can interface with bacteria associated with kidney stones, generate heat when stimulated with near infrared (NIR) light, and aid in reducing bacterial burden. Methods Two types of kidney stones, artificial, and those removed during percutaneous nephrolithotomy (PCNL), were inoculated with Escherichia coli (E. coli) and then incubated with NPs composed of FITC-labeled Poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b′]-dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe). Association of the PCPDTBSe NPs was evaluated using fluorescence microscopy. Infected stones were incubated with NPs and exposed to 800 nm light to generate temperature increases from 25.4 to 68.6 °C on the stones. Following photothermal treatment, the stones were homogenized and the bacteria was enumerated via colony counting assays to evaluate the bactericidal effect. The photothermal effect was also evaluated using scanning electron microscopy of the treated biofilms. Results Both kidney stone types sequestered E. coli. Control stones and stones treated with laser only had growth of numerous bacterial colonies, while stones exposed to NPs and laser grew significantly less, or none (p = 0.02). Conclusions The polymer NPs interface with E. coli on artificial and patient-derived kidney stones, and they can impart a bactericidal effect, when stimulated with NIR to generate heat. This technique may possibly be extended to treating infected kidney stones in patients.

Introduction Metastatic colorectal cancer (CRC) is complicated by chemotherapy-resistant cell populations. Oxaliplatin is used in heated intraperitoneal hyperthermic chemoperfusion (HIPEC) for treatment of disseminated CRC. Photothermal nanoparticles can provide focal heating to improve the response of CRC cells to oxaliplatin, by confining heating near individual cells. Reduction in cellular luciferase signal may allow single-cell-resolution recording of thermal dosimetry. Methods Oxaliplatin resistant (OxR) variants of luciferase-expressing CT26.WT-Fluc-Neo CRC cells were developed and their sensitivity to hyperthermia was evaluated. Polymer-based photothermal nanoparticles were developed, characterized and used to explore their potential for imparting a thermal dose to improve cell response to oxaliplatin. A correlation of thermal dose to intracellular luciferase activity was established using quantitative luminescence monitoring and microscopy. Results Luciferase-based monitoring of thermal dose within CT26 cell lines was validated within the ranges of 0.04–8.33 CEM43 for parental cells and 0.05–9.74 CEM43 for OxR CT26 cells. This was further confirmed using nanoparticle-induced hyperthermia, where the single-cell resolution of the thermal dose can be achieved. The nanoparticles enhance cell killing of resistant cells when combined with oxaliplatin and stimulated to generate heat. Conclusion Nanoparticle-based hyperthermia is effective for augmenting chemotherapy and can be coupled with reductions in CT26 luciferase expression to monitor thermal dose at single-cell resolution. The development of OxR CT26.WT-Fluc-Neo CRC cells sets the stage for pre-clinical evaluations to measure nanoparticle-induced hyperthermia to augment chemotherapy (Nano-HIPEC) in a chemotherapy-resistant model of disseminated CRC.

Abstract Colorectal cancer (CRC) treatment is currently hindered by micrometastatic relapse that cannot be removed completely during surgery and is often chemotherapy resistant. Targeted theranostic nanoparticles (NPs) that can produce heat for ablation and enable tumor visualization via their fluorescence offer advantages for detection and treatment of disseminated small nodules. A major hurdle in clinical translation of nanoparticles is their interaction with the 3D tumor microenvironment. To address this problem tumor organoid technology was used to evaluate the ablative potential of CD44-targeted polymer nanoparticles using hyaluronic acid (HA) as the targeting agent and coating it onto hybrid donor acceptor polymer particles (HDAPPs) to form HA-HDAPPs. Additionally, nanoparticles composed from only the photothermal polymer, poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b’]dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe), were also coated with HA, to form HA-BSe NPs, and evaluated in 3D. Monitoring of nanoparticle transport in 3D organoids revealed uniform diffusion of non-targeted HDAPPs in comparison to attenuated diffusion of HA-HDAPPs due to nanoparticle-matrix interactions. Computational diffusion profiles suggested that HA-HDAPPs transport may not be accounted for by diffusion alone, which is indicative of nanoparticle/cell matrix interactions. Photothermal activation revealed that only HA-BSe NPs were able to significantly reduce tumor cell viability in the organoids. Despite limited transport of the CD44-targeted theranostic nanoparticles, their targeted retention provides increased heat for enhanced photothermal ablation in 3D, which is beneficial for assessing nanoparticle therapies prior to in vivo testing.

Background: Many patients with rosacea join online support groups to gather and disseminate information about disease management and provide emotional support for others. Objective: To better understand rosacea patient’s primary concerns for the disease as well as their disease search patterns online. Methods: Overall, 207,038 posts by 41,400 users were collected from June 1, 2017, to June 1, 2022, in a popular online forum. We applied Latent Dirichlet Allocation (LDA), an unsupervised machine learning model, to organize the posts into topics. Keywords for each topic supplied by LDA were used to manually assign topic and category labels. Results: Twenty-three significant topics of conversation were identified and organized into 4 major categories, including Management (50.33%), Clinical Presentation (24.14%), Emotion (21.97%), and Information Appraisal (3.57%). Limitations: Although we analyzed the largest forum on the internet for rosacea, generalizability is limited given the presence of other smaller forums and the skewed demographics of forum users. Conclusion: Social media forums play an important role for disease discussion and emotional venting. Although rosacea management was the most frequently discussed topic, emotional posting was a significantly prevalent occurrence.

Psoriasis is a chronic skin disorder, and patients encounter high physical and psychosocial burdens. Social media forums feature extensive patient-generated comments. We hypothesized that analyzing patient-posted comments using natural language processing would provide insights into patient engagements, sentiments, concerns, and support, which are vital for the holistic management of psoriasis. We collected 32,000 active user comments posted on Reddit-forum. We applied Latent Dirichlet Allocation to categorize posts into popular topics and employed spectral clustering to establish cohesive themes and word representation frequency within these topics. We sorted posts into 29 significant topics of discussion and categorized them into four categories: management (37.48%), emotion (21.57%), presentation (19.79%), and others (3.57%). The frequent posts on management were diet (7.23%), biologics (6.95%), and adverse-effects (3.88%). Emotion category comprised negative sentiments (11.02%), encouragement (5.49%), and gratitude (5.06%). Presentation topic included a discussion of scalp (5.69%), flare-timing (3.63%), and arthritis (2.64%). Others comprised differential-diagnosis (5.01%), leaky gut (4.12%), and referrals (3.70%). This study identified patients’ experiences and perspectives associated with psoriasis, which should be considered to tailor support systems to improve their quality of life.

Abstract The emergence of a novel pathogen in a susceptible population can cause rapid spread of infection. High prevalence of SARS-CoV-2 infection in white-tailed deer (Odocoileus virginianus) has been reported in multiple locations, likely resulting from several human-to-deer spillover events followed by deer-to-deer transmission. Knowledge of the risk and direction of SARS-CoV-2 transmission between humans and potential reservoir hosts is essential for effective disease control and prioritisation of interventions. Using genomic data, we reconstruct the transmission history of SARS-CoV-2 in humans and deer, estimate the case finding rate and attempt to infer relative rates of transmission between species. We found no evidence of direct or indirect transmission from deer to human. However, with an estimated case finding rate of only 4.2%, spillback to humans cannot be ruled out. The extensive transmission of SARS-CoV-2 within deer populations and the large number of unsampled cases highlights the need for active surveillance at the human–animal interface.

Most of the dairy products sold in the market in Indonesia are animal milk but those products cannot be consumed by people with lactose intolerance and allergies. Plant-based milk is an alternative substitute for animal milk, and the most widely known is soy milk, but the production of soybeans in Indonesia is low. Jack beans (Canavalia ensiformis) are an alternative raw material substitute for plant-based milk. Meanwhile, the protein content of jack beans is similar to soybeans, but it is not popular as a food ingredient. This study aims to obtain the acceptable combination factors in processing jack bean milk. A full factorial design experiment was conducted to analyze the effect of temperature and heating duration on the specific gravity of jack bean milk and its organoleptic properties such as color, aroma, taste, and texture. The results showed that the temperature and heating time influenced the specific gravity and organoleptic properties of jack bean milk. In addition, the best combination of factors and levels is at a heating temperature of 100 °C for 20 minutes, which results in the specific gravity of jack bean milk, which is 1.0758.

There is mounting evidence of SARS-CoV-2 spillover from humans into many domestic, companion, and wild animal species. Research indicates that humans have infected white-tailed deer, and that deer-to-deer transmission has occurred, indicating that deer could be a wildlife reservoir and a source of novel SARS-CoV-2 variants. We examined the hypothesis that the Omicron variant is actively and asymptomatically infecting the free-ranging deer of New York City. Between December 2021 and February 2022, 155 deer on Staten Island, New York, were anesthetized and examined for gross abnormalities and illnesses. Paired nasopharyngeal swabs and blood samples were collected and analyzed for the presence of SARS-CoV-2 RNA and antibodies. Of 135 serum samples, 19 (14.1%) indicated SARS-CoV-2 exposure, and 11 reacted most strongly to the wild-type B.1 lineage. Of the 71 swabs, 8 were positive for SARS-CoV-2 RNA (4 Omicron and 4 Delta). Two of the animals had active infections and robust neutralizing antibodies, revealing evidence of reinfection or early seroconversion in deer. Variants of concern continue to circulate among and may reinfect US deer populations, and establish enzootic transmission cycles in the wild: this warrants a coordinated One Health response, to proactively surveil, identify, and curtail variants of concern before they can spill back into humans.

More than 93 percent of parents place high importance on sex education in both middle and high school. Sex education in middle and high school is widely supported by parents regardless of their political affiliation. Using data from a large diverse sample of 1,633 parents of children aged 9 to 21 years, we examined whether views on sex education differed by parents' political affiliation. More than 89 percent of parents that identified as Republicans or Democrats support including a wide range of topics in sex education including puberty, healthy relationships, abstinence, sexually transmitted diseases (STDs) and birth control in high school. In middle school, 78 percent or more of both parents that identified as Republicans and Democrats support the inclusion of those topics. Controlling for key demographic factors, parents that identified as Democrats are more likely than those that identified as Republicans to support the inclusion of the topics of healthy relationships, birth control, STDs, and sexual orientation in both middle and high school. However, a strong majority of Republican parents want all these topics included in sex education. Sex education which includes a broad set of topics represents an area of strong agreement between parents of both political parties.