Focused Insights into Liposomal Nanotherapeutics for Antimicrobial Treatment.

Addressing infectious conditions presents a formidable challenge, primarily due to the escalating issue of bacterial resistance. This, coupled with limited financial resources and stagnant antibiotic research, compounds the antibiotic crisis. Innovative strategies, including novel antibiotic development and alternative solutions, are crucial to combat microbial resistance. Nanotherapeutics offers a promising approach to enhance drug delivery systems. Integration into lipid-based nanoscale delivery systems, particularly through therapeutic substance encapsulation in liposomal carriers, significantly prolongs drug presence at infection sites. This not only reduces toxicity but also shields antibiotics from degradation. Lipidic carriers, particularly liposomes, exhibit remarkable specificity in targeting infectious cells. This holds great promise in combating antimicrobial resistance and potentially transforming treatment for multi-drug resistant infections. Leveraging liposomal carriers may lead to breakthroughs in addressing drugresistant bacterial infections. This review emphasizes the potential of antimicrobial-loaded liposomes as a novel delivery system for bacterial infections. Encapsulating antimicrobial agents within liposomes enhances treatment efficiency. Moreover, liposomal systems counteract challenges posed by antimicrobial resistance, offering hope in managing persistent multidrug-resistant infections. In the battle against bacterial resistance and the antibiotics crisis, the use of antimicrobial-loaded liposomes as delivery vehicles shows great promise. This innovative approach not only extends drug effectiveness and reduces toxicity but also provides a path to address highly resistant infectious conditions. As research advances, liposomal nanotherapeutics may emerge as a transformative solution in the fight against bacterial infections.

Positive space acquiring asymmetric membranes for guiding alveolar bone regeneration under infectious conditions.

To obtain multifunctional materials suitable for guiding alveolar bone regeneration under infectious conditions, we prepared asymmetric membranes comprising space acquiring layer that involves fibroblast inhibitor poly(p-dioxanone-co-L-phenylalanine) (PDPA), an isolating dense layer that forms barrier between two layers and an osteogenesis inducing electrospinning layer which involves hydroxyapatite or hydroxyapatite & minocycline. Then the composition, crystallization, morphology, and hydrophilicity of asymmetric membranes were analyzed. Minocycline incorporated membranes controlled the expansion of Porphyromonas gingivalis (P. gingivalis) in vitro. Hydroxyapatite-incorporated asymmetric membranes promoted the expression of osteogenesis related genes RUNX2, OPN, ALP of MC3T3-E1 cells in vitro. The mineralization of MC3T3-E1 cells cultured with hydroxyapatite-incorporated asymmetric membranes were also promoted in vitro. Asymmetric membranes especially hydroxyapatite-incorporated ones guided the regeneration of the mandibular bone defect in vivo. Bone regeneration guided under infectious conditions was evaluated in a P. gingivalis infected alveolar bone defect model. Specifically, space acquiring layer containing asymmetric membranes effectively controlled connective tissue hyperplasia at defect sites. The excellent guided bone regeneration achieved by applying a single space acquiring layer membrane further indicates the importance of acquiring space actively to induce bone regeneration. Hydroxyapatite-minocycline incorporated symmetric membranes could simultaneously suppress alveolar bone reabsorption caused by infection and guide regeneration of defects. Therefore, the hydroxyapatite-minocycline incorporated asymmetric membrane may be more suitable to be applied in guiding regeneration of bone defects under complex infectious conditions.

Benchmarking transcriptional host response signatures for infection diagnosis.

Identification of host transcriptional response signatures has emerged as a new paradigm for infection diagnosis. For clinical applications, signatures must robustly detect the pathogen of interest without cross-reacting with unintended conditions. To evaluate the performance of infectious disease signatures, we developed a framework that includes a compendium of 17,105 transcriptional profiles capturing infectious and non-infectious conditions and a standardized methodology to assess robustness and cross-reactivity. Applied to 30 published signatures of infection, the analysis showed that signatures were generally robust in detecting viral and bacterial infections in independent data. Asymptomatic and chronic infections were also detectable, albeit with decreased performance. However, many signatures were cross-reactive with unintended infections and aging. In general, we found robustness and cross-reactivity to be conflicting objectives, and we identified signature properties associated with this trade-off. The data compendium and evaluation framework developed here provide a foundation for the development of signatures for clinical application. A record of this paper's transparent peer review process is included in the supplemental information.

Combating Bovine Mastitis in the Dairy Sector in an Era of Antimicrobial Resistance: Ethno-veterinary Medicinal Option as a Viable Alternative Approach.

Bovine mastitis (BM) is the traditional infectious condition in reared cattle which may result in serious repercussions ranging from animal welfare to economic issues. Owing to the high costs associated with preventative practices and therapeutic measures, lower milk output, and early culling, bovine mastitis is accountable for most of the financial losses suffered in cattle farming. Streptococcus agalactiae, Staphylococcus aureus, Streptococcus dysgalactiae and coliform bacteria are the predominant pathogens for bovine mastitis. In addition, the occurrence of BM has been linked to lactation stage and poor management, in the latter case, the poor stabling conditions around udder hygiene. BM occurs throughout the world, with varying rates of Streptococcus agalactiae infection in different regions. Despite the modern techniques, such as the appropriate milking practices that are applied, lower levels of pathogen vulnerability may help to prevent the development of the disease, BM treatment is primarily reliant on antibiotics for both prophylactic and therapeutic purposes. Nevertheless, as a result of the proliferation of bacterial agents to withstand the antibiotic effects, these therapies have frequently proven ineffectual, resulting in persistent BM. Consequently, alternative medicines for the management of udder inflammation have been researched, notably natural compounds derived from plants. This review focuses on BM in terms of its risk factors, pathogenesis, management, the molecular identification of causative agents, as well as the application of ethno-veterinary medicine as an alternative therapy.

The impact of the COVID-19 pandemic on paediatric health service use within one year after the first pandemic outbreak in New South Wales Australia - a time series analysis.

BACKGROUND: The first wave of the COVID-19 pandemic hit New South Wales (NSW) Australia in early 2020, followed by a sharp state-wide lockdown from mid-March to mid-May. After the lockdown, there had been a low level of community transmission of COVID-19 over a year. Such pandemic experiences provide unique opportunity to understand the impact of the pandemic on paediatric health service use as countries emerge from the pandemic. METHODS: We examined the difference between the observed and the predicted numbers of inpatient admissions and emergency department (ED) attendances, respectively, related to chronic, acute infectious and injury conditions, for each month during the COVID-19 period (January 2020-February 2021), based on the numbers from 2016 to 2019, using records from two major paediatric hospitals in NSW. All analyses were conducted using autoregressive error models and were stratified by patient age, sex and socioeconomic status. FINDINGS: Health service use was significantly lower than predicted for admissions and/or ED attendances related to chronic conditions, acute infections, and injury during the lockdown in 2020. Change in health service use varied by chronic conditions, from the largest decrease for respiratory conditions (40-78%) to non-significant change for cancer and mental health disorders. After the lockdown, health service use for most health conditions returned to pre-COVID-19 predicted levels. However, for mental health disorders, increased health service use persisted from June 2020 up to February 2021 by 30-55%, with higher increase among girls aged 12-17 years and those from socioeconomically advantaged areas. There was persistently lower health service use for acute infections and increased health service use for injuries. Differences by socio-demographic factors were noted for mental health disorders and injuries. INTERPRETATION: The immediate return to pre-COVID-19 levels for most chronic conditions after the first lockdown in NSW highlights the healthcare needs for children affected by chronic conditions. Persistently lower health service use for acute infections is likely attributable to the decreased social contact. Sustained and targeted mental health support is essential to address the potentially increased demand for services among children during and beyond the pandemic. FUNDING: Financial Markets Foundation for Children Chair (RL, NN), NHMRC Investigator Grant (APP1197940) (NN), NHMRC Career Development fellowship (GNT1158954) (SW).

The Role of Macrophages During Mammalian Tissue Remodeling and Regeneration Under Infectious and Non-Infectious Conditions.

Several infectious pathologies in humans, such as tuberculosis or SARS-CoV-2, are responsible for tissue or lung damage, requiring regeneration. The regenerative capacity of adult mammals is limited to few organs. Critical injuries of non-regenerative organs trigger a repair process that leads to a definitive architectural and functional disruption, while superficial wounds result in scar formation. Tissue lesions in mammals, commonly studied under non-infectious conditions, trigger cell death at the site of the injury, as well as the production of danger signals favouring the massive recruitment of immune cells, particularly macrophages. Macrophages are also of paramount importance in infected injuries, characterized by the presence of pathogenic microorganisms, where they must respond to both infection and tissue damage. In this review, we compare the processes implicated in the tissue repair of non-infected versus infected injuries of two organs, the skeletal muscles and the lungs, focusing on the primary role of macrophages. We discuss also the negative impact of infection on the macrophage responses and the possible routes of investigation for new regenerative therapies to improve the recovery state as seen with COVID-19 patients.

Care of Infectious Conditions in an Observation Unit.

Infectious conditions such as skin and soft tissue infections (SSTIs), Urogenital infections and peritonsillar abscesses frequently require care beyond emergency stabilization and are well-suited for short term care in an observation unit. SSTIs are a growing problem, partly due to emergence of strains of methicillin-resistant S. aureus (MRSA). Antibiotic choice is guided by the presence of purulence and site of infection. Purulent cellulitis is much more likely to be associated with MRSA. Radiographic imaging should be considered to aid in management in patients who are immunosuppressed, have persistent symptoms despite antibiotic therapy, recurrent infections, sepsis or diabetes.

The anticipation and management of air leaks and residual spaces post lung resection.

The incidence of any kind of air leaks after lung resections is reportedly around 50% of patients. The majority of these leaks doesn't require any specific intervention and ceases within a few hours or days. The recent literature defines a prolonged air leak (PAL) as an air leak lasting beyond postoperative day 5. PAL is associated with a generally worse outcome with a more complicated postoperative course anxd prolonged hospital stay and increased costs. Some authors therefore consider any PAL as surgical complication. PAL is the most prevalent postoperative complication following lung resection and the most important determinant of postoperative length of hospital stay. A low predicted postoperative forced expiratory volume in 1 second (ppoFEV1) and upper lobe disease have been identified as significant risk factors involved in developing air leaks. Infectious conditions have also been reported to increase the risk of PAL. In contrast to the problem of PAL, there is only limited information from the literature regarding apical spaces after lung resection, probably because this common finding rarely leads to clinical consequences. This article addresses the pathogenesis of PAL and apical spaces, their prediction, prevention and treatment with a special focus on surgery for infectious conditions. Different predictive models to identify patients at higher risk for the development of PAL are provided. The discussion of surgical treatment options includes the use of pneumoperitoneum, blood patch, intrabronchial valves (IBV) and the flutter valve, and addresses the old question, whether or not to apply suction to chest tubes. The discussed prophylactic armentarium comprises of pleural tenting, prophylactic intraoperative pneumoperitoneum, sealing of the lung, buttressing of staple lines, capitonnage after resection of hydatid cysts, and plastic surgical options.