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Cureus May 2024Folliculitis decalvans (FD) is a rare type of inflammatory scalp disorder that leads to scarring alopecia. It is classified as primary neutrophilic cicatricial...
Folliculitis decalvans (FD) is a rare type of inflammatory scalp disorder that leads to scarring alopecia. It is classified as primary neutrophilic cicatricial alopecia. FD presents a challenging scenario in clinical dermatology due to its rarity, resistance to treatment, and potential for scarring alopecia. This inflammatory scalp disorder primarily affects middle-aged adults, predominantly males. While its exact pathogenesis remains uncertain, a deficient host immune response to Staphylococcus aureus infection is hypothesized. Therapeutic interventions for FD pose difficulties, with limited treatment options available A 58-year-old female patient presented with a history of follicular papules that gradually progressed to form clusters of pustules, crusting, and hemorrhagic lesions with tufting of hairs on the crown area of the scalp, and was diagnosed with FD. Considering isotretinoin's role in inhibiting abnormal keratinization and inflammation, and rifampicin's ability to eradicate S. aureus, the combination of both provides a comprehensive approach to tackling the underlying factors contributing to FD. Despite previous unsuccessful treatments, combination therapy with isotretinoin and rifampicin yielded a remarkable outcome, prompting further exploration of this approach.
PubMed: 38903375
DOI: 10.7759/cureus.60633 -
BioRxiv : the Preprint Server For... Feb 2024Septic shock, in humans and in our well-established animal model, is associated with increases in biventricular end diastolic volume (EDV) and decreases in ejection...
BACKGROUND
Septic shock, in humans and in our well-established animal model, is associated with increases in biventricular end diastolic volume (EDV) and decreases in ejection fraction (EF). These abnormalities occur over 2 days and reverse within 10 days. Septic non-survivors do not develop an increase in EDV. The mechanism for this cardiac dysfunction and EDV differences is unknown.
METHODS
Purpose-bred beagles randomized to receive intrabronchial (n=27) or saline (n=6) were provided standard ICU care including sedation, mechanical ventilation, and fluid resuscitation to a pulmonary arterial occlusion pressure of over 10mmHg. No catecholamines were administered. Over 96h, cardiac magnetic resonance imaging, echocardiograms, and invasive hemodynamics were serially performed, and laboratory data was collected. Tissue was obtained at 66h from six septic animals.
RESULTS
From 0-96h after bacterial challenge, septic animals controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%) which was more pronounced at 48h in non-survivors than survivors. On histology, edema was located predominantly in myocytes, the interstitium, and endothelial cells. Edema was associated with significantly worse biventricular function (lower EFs), ventricular-arterial coupling, and circumferential strain. In septic animals, from 0-24h, the EDV decreased from baseline and, despite cardiac filling pressures being similar, decreased significantly more in non-survivors. From 24-48h, all septic animals had increases in biventricular chamber sizes. Survivors biventricular EDVs were significantly greater than baseline and in non-survivors, where biventricular EDVs were not different from baseline. Preload, afterload, or HR differences did not explain these differential serial changes in chamber size.
CONCLUSION
Systolic and diastolic cardiac dysfunction during sepsis is associated with ventricular wall edema. Rather than differences in preload, afterload, or heart rate, structural alterations to the ventricular wall best account for the volume changes associated with outcome during sepsis. In non-survivors, from 0-24h, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part explain, the EDV increases from 24-48h. However, these changes continued and even accelerated into the recovery phase consistent with a reparative process rather than ongoing injury.
CLINICAL PERSPECTIVE
Utilizing multimodal imaging and hemodynamics, we demonstrate the cardiac changes of sepsis have injury and reparative phases.The injury phase (0-24h) has EDV decreases more profound in non-survivors and is associated with worse ventricular compliance, myocardial edema, and diastolic dysfunction.The recovery phase has left ventricular mass loss with wall thinning in survivors that explains the EDV increases (24-96h). These progressed into the EF recovery phase consistent with a reparative process removing damaged tissue.This is the first controlled CMR sepsis study supporting ventricular wall edema is a fundamental aspect of sepsis pathophysiology and dry mass loss a reparative mechanism. Despite optimizing filling pressures, the cardiac changes in ventricular wall structure and function associated with survival and non-survival in sepsis still occurred, thereby discounting fluid resuscitation as the major factor of therapeutic importance for cardiac function and survival.The changes reported here have potential implications for sepsis treatment especially in the field of fluid resuscitation. These findings yield new understanding into the pathophysiology of sepsis cardiac dysfunction and allow for novel phenotyping and prognosticating of the syndrome with ventricular compliance and EDVs. This also offers potentially high yielding targets for research for new therapeutic approaches for sepsis and heart failure.
PubMed: 38903100
DOI: 10.1101/2024.02.05.578971 -
Scientific Reports Jun 2024The antibiotic fusidic acid (FA) is used to treat Staphylococcus aureus infections. It inhibits protein synthesis by binding to elongation factor G (EF-G) and preventing...
The antibiotic fusidic acid (FA) is used to treat Staphylococcus aureus infections. It inhibits protein synthesis by binding to elongation factor G (EF-G) and preventing its release from the ribosome after translocation. While FA, due to permeability issues, is only effective against gram-positive bacteria, the available structures of FA-inhibited complexes are from gram-negative model organisms. To fill this knowledge gap, we solved cryo-EM structures of the S. aureus ribosome in complex with mRNA, tRNA, EF-G and FA to 2.5 Å resolution and the corresponding complex structures with the recently developed FA derivative FA-cyclopentane (FA-CP) to 2.0 Å resolution. With both FA variants, the majority of the ribosomal particles are observed in chimeric state and only a minor population in post-translocational state. As expected, FA binds in a pocket between domains I, II and III of EF-G and the sarcin-ricin loop of 23S rRNA. FA-CP binds in an identical position, but its cyclopentane moiety provides additional contacts to EF-G and 23S rRNA, suggesting that its improved resistance profile towards mutations in EF-G is due to higher-affinity binding. These high-resolution structures reveal new details about the S. aureus ribosome, including confirmation of many rRNA modifications, and provide an optimal starting point for future structure-based drug discovery on an important clinical drug target.
Topics: Fusidic Acid; Staphylococcus aureus; Ribosomes; Cyclopentanes; Peptide Elongation Factor G; Cryoelectron Microscopy; Anti-Bacterial Agents; Models, Molecular; RNA, Transfer
PubMed: 38902339
DOI: 10.1038/s41598-024-64868-x -
PloS One 2024Wild chimpanzees consume a variety of plants to meet their dietary needs and maintain wellbeing. While some plants have obvious value, others are nutritionally poor...
Wild chimpanzees consume a variety of plants to meet their dietary needs and maintain wellbeing. While some plants have obvious value, others are nutritionally poor and/or contain bioactive toxins which make ingestion costly. In some cases, these nutrient-poor resources are speculated to be medicinal, thought to help individuals combat illness. In this study, we observed two habituated chimpanzee communities living in the Budongo Forest, Uganda, and collected 17 botanical samples associated with putative self-medication behaviors (e.g., bark feeding, dead wood eating, and pith-stripping) or events (e.g., when consumer had elevated parasite load, abnormal urinalysis, or injury). In total, we selected plant parts from 13 species (nine trees and four herbaceous plants). Three extracts of different polarities were produced from each sample using n-hexane, ethyl acetate, and methanol/water (9/1, v/v) and introduced to antibacterial and anti-inflammatory in vitro models. Extracts were evaluated for growth inhibition against a panel of multidrug-resistant clinical isolates of bacteria, including ESKAPE strains and cyclooxygenase-2 (COX-2) inhibition activity. Pharmacological results suggest that Budongo chimpanzees consume several species with potent medicinal properties. In the antibacterial library screen, 45 out of 53 extracts (88%) exhibited ≥40% inhibition at a concentration of 256 μg/mL. Of these active extracts, 41 (91%) showed activity at ≤256μg/mL in subsequent dose-response antibacterial experiments. The strongest antibacterial activity was achieved by the n-hexane extract of Alstonia boonei dead wood against Staphylococcus aureus (IC50: 16 μg/mL; MIC: 32 μg/mL) and Enterococcus faecium (IC50: 16 μg/mL; MIC: >256 μg/mL) and by the methanol-water extract of Khaya anthotheca bark and resin against E. faecium (IC50: 16 μg/mL; MIC: 32 μg/mL) and pathogenic Escherichia coli (IC50: 16 μg/mL; MIC: 256 μg/mL). We observed ingestion of both these species by highly parasitized individuals. K. anthotheca bark and resin were also targeted by individuals with indicators of infection and injuries. All plant species negatively affected growth of E. coli. In the anti-inflammatory COX-2 inhibition library screen, 17 out of 51 tested extracts (33%) showed ≥50% COX-2 inhibition at a concentration of 5 μg/mL. Several extracts also exhibited anti-inflammatory effects in COX-2 dose-response experiments. The K. anthotheca bark and resin methanol-water extract showed the most potent effects (IC50: 0.55 μg/mL), followed by the fern Christella parasitica methanol-water extract (IC50: 0.81 μg/mL). This fern species was consumed by an injured individual, a feeding behavior documented only once before in this population. These results, integrated with associated observations from eight months of behavioral data, provide further evidence for the presence of self-medicative resources in wild chimpanzee diets. This study addresses the challenge of distinguishing preventative medicinal food consumption from therapeutic self-medication by integrating pharmacological, observational, and health monitoring data-an essential interdisciplinary approach for advancing the field of zoopharmacognosy.
Topics: Animals; Pan troglodytes; Plant Extracts; Plants, Medicinal; Uganda; Anti-Bacterial Agents; Diet; Behavior, Animal; Feeding Behavior
PubMed: 38900778
DOI: 10.1371/journal.pone.0305219 -
PloS One 2024Implant-associated osteomyelitis remains a major orthopaedic problem. As neutrophil swarming to the surgical site is a critical host response to prevent infection,...
Implant-associated osteomyelitis remains a major orthopaedic problem. As neutrophil swarming to the surgical site is a critical host response to prevent infection, visualization and quantification of this dynamic behavior at the native microenvironment of infection will elucidate previously unrecognized mechanisms central to understanding the host response. We recently developed longitudinal intravital imaging of the bone marrow (LIMB) to visualize host cells and fluorescent S. aureus on a contaminated transfemoral implant in live mice, which allows for direct visualization of bacteria colonization of the implant and host cellular responses using two-photon laser scanning microscopy. To the end of rigorous and reproducible quantitative outcomes of neutrophil swarming kinetics in this model, we developed a protocol for robust segmentation, tracking, and quantifications of neutrophil dynamics adapted from Trainable Weka Segmentation and TrackMate, two readily available Fiji/ImageJ plugins. In this work, Catchup mice with tdTomato expressing neutrophils received a transfemoral pin with or without ECFP/EGFP-expressing USA300 methicillin-resistant Staphylococcus aureus (MRSA) to obtain 30-minute LIMB videos at 2-, 4-, and 6-hours post-implantation. The developed semi-automated neutrophil tracking protocol was executed independently by two users to quantify the distance, displacement, speed, velocity, and directionality of the target cells. The results revealed high inter-user reliability for all outcomes (ICC > 0.96; p > 0.05). Consistent with the established paradigm on increased neutrophil swarming during active infection, the results also demonstrated increased neutrophil speed and velocity at all measured time points, and increased displacement at later time points (6 hours) in infected versus uninfected mice (p < 0.05). Neutrophils and bacteria also exhibit directionality during migration in the infected mice. The semi-automated cell tracking protocol provides a streamlined approach to robustly identify and track individual cells across diverse experimental settings and eliminates inter-observer variability.
Topics: Animals; Neutrophils; Mice; Femur; Cell Tracking; Staphylococcal Infections; Disease Models, Animal; Osteomyelitis; Methicillin-Resistant Staphylococcus aureus; Prosthesis-Related Infections; Prostheses and Implants; Staphylococcus aureus; Female
PubMed: 38900759
DOI: 10.1371/journal.pone.0296140 -
Antimicrobial Agents and Chemotherapy Jun 2024Delafloxacin, a fluoroquinolone antibiotic to treat skin infections, exhibits a broad-spectrum antimicrobial activity. The first randomized, open-label phase I clinical...
Delafloxacin, a fluoroquinolone antibiotic to treat skin infections, exhibits a broad-spectrum antimicrobial activity. The first randomized, open-label phase I clinical trial was conducted to assess the safety and pharmacokinetics (PK) of intravenous delafloxacin in the Chinese population. A population pharmacokinetic (PopPK) model based on the clinical trial was conducted by NONMEM software. Monte Carlo simulation was performed to evaluate the antibacterial effects of delafloxacin at different doses in different Chinese populations. The PK characteristics of delafloxacin were best described by a three-compartment model with mixed linear and nonlinear clearance. Body weight was included as a covariate in the model. We simulated the AUC in a steady state at five doses in patient groups of various weights. The results indicated that for patients weighing 70 kg and treated with methicillin-resistant (MRSA) infections, a minimum dose of 300 mg achieved a PTA > 90% at MIC of 0.25 µg/mL, suggesting an ideal bactericidal effect. For patients weighing less than 60 kg, a dose of 200 mg achieved a PTA > 90% at MIC of 0.25 µg/mL, also suggesting an ideal bactericidal effect. Additionally, this trial demonstrated the high safety of delafloxacin in single-dose and multiple-dose groups of Chinese. Delafloxacin (300 mg, q12h, iv) was recommended for achieving optimal efficacy in Chinese bacterial skin infections patients. To ensure optimal efficacy, an individualized dose of 200 mg (q12h, iv) could be advised for patients weighing less than 60 kg, and 300 mg (q12h, iv) for those weighing more than 60 kg.
PubMed: 38899925
DOI: 10.1128/aac.00428-24 -
BioMed Research International 2024In a research experiment, 48 male Wistar rats were anesthetized and second-degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with...
MATERIALS AND METHODS
In a research experiment, 48 male Wistar rats were anesthetized and second-degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with MRSA. Various treatments were applied to the burn wounds daily, including Myrtus ointment, silver nanoparticles, silver nanoparticles-Myrtus ointment, silver sulfadiazine-Myrtus ointment, silver sulfadiazine 1%, mupirocin ointment, and a positive control. The study measured the antimicrobial effects, wound area, percentage of wound healing, antioxidant capacities, malondialdehyde, and nitric oxide concentrations in the serum of the rats. Data analysis was performed using GraphPad software, with one-way ANOVA and Tukey's tests used to determine the statistical significance of the results.
RESULTS
Rats treated with Myrtus ointment, silver nanoparticles-Myrtus ointment, and mupirocin had reduced bacterial growth compared to the positive control group, nanoparticle ointment, and silver sulfadiazine ( < 0.05). The wound area of the Myrtus ointment group decreased significantly on the seventh and fourteenth days, as well as the level of MDA and nitric oxide, compared to the other groups. In Myrtus and silver sulfadiazine-Myrtus ointment increased the thickness of the epidermis and dermis compared to the other groups.
CONCLUSION
Based on the anti-inflammatory, antimicrobial, and wound healing properties of Myrtus, with further studies, an ointment of this plant may be used as a main or complementary treatment for burn wound infections caused by MRSA.
Topics: Animals; Wound Healing; Methicillin-Resistant Staphylococcus aureus; Burns; Plant Extracts; Male; Ointments; Rats; Rats, Wistar; Anti-Inflammatory Agents; Plant Leaves; Myrtus; Anti-Infective Agents; Wound Infection; Staphylococcal Infections; Metal Nanoparticles; Silver Sulfadiazine
PubMed: 38899039
DOI: 10.1155/2024/6758817 -
TheScientificWorldJournal 2024Ethnomedicinally, more than 2000 plants were found to be used in Nepal. Among them, the red colored rhizome of and the bark of have been used widely to treat muscle...
Ethnomedicinally, more than 2000 plants were found to be used in Nepal. Among them, the red colored rhizome of and the bark of have been used widely to treat muscle fatigue, bone pain, fever, postpartum hemorrhage, and thirst by healers in Kaski and Tanahun districts, Nepal. However, scientific evidence towards their traditional uses is lacking till December, 2023. Therefore, we report the phytochemicals, total phenolic content (TPC), total flavonoid content (TFC), total carbohydrate content (TCC), antioxidant and antibacterial activities of and extracts. Phytochemical analysis indicated that and extracts were potential sources of chemicals such as phenols, flavonoids, tannins, terpenoids, saponins, and carbohydrates. The TPC, TFC, and TCC of extracts were determined by using an ultraviolet visible spectrophotometer. Among the extracts tested, extracts showed the highest phenolic and carbohydrate contents of 208.33 ± 12.96 mg of gallic acid equivalent/g and 564.16 ± 2.92 mg of D-glucose equivalent/g of dry extract, respectively. Similarly, revealed the highest flavonoid content of 30.35 ± 0.1 mg quercetin equivalent/g of dry extract. The extract of and exhibited potent antioxidant activity by scavenging 2,2-diphenyl-1-picrylhydrazyl radicals with an IC of 25.9 g/ml and 31.07 g/ml, respectively. The antibacterial activity of the and extract against , and was determined using an agar-well diffusion protocol that revealed the potential antibacterial activity of against . The present study will help validate the traditional uses of rhizomes and barks as a healing medicine and inspire the researcher towards further research, development, and formulation.
Topics: Antioxidants; Anti-Bacterial Agents; Plant Extracts; Phytochemicals; Plant Bark; Rhizome; Nepal; Flavonoids; Microbial Sensitivity Tests; Phenols
PubMed: 38898935
DOI: 10.1155/2024/1119165 -
BMC Research Notes Jun 2024The purpose of this study was to evaluate antibacterial activity of pigment extracted from bacteria, isolated from soil samples. During the study, 20 soil samples were...
The purpose of this study was to evaluate antibacterial activity of pigment extracted from bacteria, isolated from soil samples. During the study, 20 soil samples were collected from different areas (forest, agriculture fields, river sides and dumping sites) of Kathmandu and Lalitpur districts which were processed for isolation of pigment producing bacteria by spread plate technique. The pigmented bacterial isolates were identified and enriched in nutrient broth. Then, pigment was extracted in 95% methanol as solvent, which was further characterized using UV-Vis Spectrophotometric and TLC analysis. The obtained crude pigment extract was processed to carry out the antimicrobial susceptibility assay using agar well diffusion method. Out of 13 total pigmented bacteria isolates, four different colored pigmented bacterial isolates (S4O, S11Y, S14P and S17G) which produced efficient pigment on nutrient agar were chosen and they were further processed. Among these isolates, S4O was identified as Staphylococcus aureus, S11Y was identified as Micrococcus luteus, S14P was identified as Micrococcus roseus and S17G was identified as Pseudomonas aeruginosa respectively. On characterization using UV-Vis Spectrophotometric and TLC analysis, the pigment extracted from isolates S4O, S11Y and S14P were found to be Carotenoids and from isolate S17G was found to be Pyocyanin in nature. The maximum antibacterial activity was shown against Staphylococcus aureus from all the four pigments extracts. The green color pigment extract from isolate S17G was found to be most effective against all the Gram-positive and Gram-negative test bacteria. This study suggests that these pigment extracts from pigmented bacteria may have beneficial antibacterial roles that can be exploited in controlling unwanted bacterial growth.
Topics: Anti-Bacterial Agents; Soil Microbiology; Pigments, Biological; Microbial Sensitivity Tests; Staphylococcus aureus; Pseudomonas aeruginosa; Bacteria; Micrococcus luteus
PubMed: 38898523
DOI: 10.1186/s13104-024-06834-4 -
Clinical Microbiology and Infection :... Jun 2024This review aims to explore the characteristics of outbreaks of community-acquired community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) in low... (Review)
Review
OBJECTIVES
This review aims to explore the characteristics of outbreaks of community-acquired community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) in low prevalence areas, to understand the factors involved in its rise, and to translate this knowledge into public health policy and further research needs.
SOURCES
PubMed, EMBASE and Google Scholar were searched using combinations of the terms "transmission", "acquisition", "CA-MRSA" "MRSA", "community-acquired", "low prevalence", "genomic", "outbreak", "colonisation" and "carriage". Wherever evidence was limited, additional articles were sought specifically, via PubMed searches. Papers where materials were not available in English were excluded.
CONTENT
Community-acquired, community onset MRSA infection presents a significant public health challenge, even in low prevalence areas; where MRSA rates are historically lower. Despite successes in reducing hospital-onset MRSA (HO-MRSA), CO-MRSA rates are increasing globally, with a need to understand this trend, and the potential risk factors for re-emergence. Challenges in defining low prevalence areas and the significance of exposure to various risk factors for community acquisition, such as healthcare settings, travel, livestock, and environmental factors, are discussed. The importance of genomic surveillance in identifying outbreak strains and understanding the transmission dynamics is highlighted, along with the need for robust public health policies and control measures.
IMPLICATIONS
The findings emphasise the complexity of CO-MRSA transmission and the necessity of a multifaceted approach in low prevalence areas. This includes integrated and systematic surveillance of HO-, CO-, and livestock-associated MRSA (LA-MRSA), as has been effective in some Northern European countries. The evolution of CO-MRSA underscores the need for global collaboration, routine genomic surveillance, and comprehensive antimicrobial stewardship to mitigate the rise of CO-MRSA and address the broader challenge of antimicrobial resistance. These efforts are crucial for maintaining low MRSA prevalence and managing the increasing burden of CO-MRSA in both low and higher prevalence regions.
PubMed: 38897351
DOI: 10.1016/j.cmi.2024.06.006