66 research outputs found
Bacterial Biofilm in Chronic Wounds and Possible Therapeutic Approaches
No full textWound repair and skin regeneration is a very complex orchestrated process that is generally composed of four phases: hemostasis, inflammation, proliferation, and remodeling. Each phase involves the activation of different cells and the production of various cytokines, chemokines, and other inflammatory mediators affecting the immune response. The microbial skin composition plays an important role in wound healing. Indeed, skin commensals are essential in the maintenance of the epidermal barrier function, regulation of the host immune response, and protection from invading pathogenic microorganisms. Chronic wounds are common and are considered a major public health problem due to their difficult-to-treat features and their frequent association with challenging chronic infections. These infections can be very tough to manage due to the ability of some bacteria to produce multicellular structures encapsulated into a matrix called biofilms. The bacterial species contained in the biofilm are often different, as is their capability to influence the healing of chronic wounds. Biofilms are, in fact, often tolerant and resistant to antibiotics and antiseptics, leading to the failure of treatment. For these reasons, biofilms impede appropriate treatment and, consequently, prolong the wound healing period. Hence, there is an urgent necessity to deepen the knowledge of the pathophysiology of delayed wound healing and to develop more effective therapeutic approaches able to restore tissue damage. This work covers the wound-healing process and the pathogenesis of chronic wounds infected by biofilm-forming pathogens. An overview of the strategies to counteract biofilm formation or to destroy existing biofilms is also provided
Optics and theory of vision in the Kitāb nūr al-'uyūn wa-jāmi' al-funūn: critical edition, translation and comment of the second maqāla
No full textScience changes constantly. Most of the time, progress involves minor issues or specific elements of inquiry. Much more rarely, instead, the foundational paradigms evolve, entailing processes of conceptual re-elaboration which re-define the disciplines anew. Let us consider optics. The re-definition of the discipline as the physics of light is quite recent. Throughout Antiquity and the Middle Ages, its status was completely different. Optics was in fact conceived as the science of vision, the eye being its primary element of investigation, rather than light. Such a paradigmatic link warranted a special connection between optics and medicine, namely with ophthalmology. The medieval Arabic production in this field is a case in point inasmuch as the lion’s share of its texts usually presents a section devoted to optics. Within this tradition, deeply influenced by the ancient Greek legacy, the Kitāb nūr al-ʿuyūn wa-ǧāmiʿ al-funūn stands out. Contrary to a standard, unoriginal treatment of the ophthalmological issues, the contents, sources, and general setup of its second maqāla, entirely devoted to optical matters, is as peculiar as to make this work a unicum in the field of medieval Arabic ophthalmology. Centered on the examination of this section, this study aims to produce a critical edition thereof, integrated with an annotated translation. Before that, a contextualization of the Kitāb nūr al-ʿuyūn wa-ǧāmiʿ al-funūn is provided in Chapter One. The first paragraph introduces the work regarding its main contents, setup, and approach. A brief overview concerning the state of the art on the Kitāb nūr al-ʿuyūn wa-ǧāmiʿ al-funūn is presented afterwards. The second paragraph focuses on the second maqāla, which is examined upon the background of the Arabic medieval literary production on ophthalmology. By means of retracing models and patterns regarding the treatment of optical matters within the most famous works in the field, the uniqueness of the maqāla is established. The third paragraph deals with diagrams, pivotal elements of Euclidean geometrical optics. In particular, diagrams are examined with regard to their paleographical-codicological peculiarities, in order to shed some light upon issues relating to the material culture, as well as to investigate how diagrams interact with the leaf and the mathematical content they refer to. The fourth paragraph is reserved to the author of the Kitāb nūr al-ʿuyūn wa-ǧāmiʿ al-funūn, Abū Zakariyyā Yaḥyā b. Abī al-Raǧāʾ. This section is structured as an attempt at sketching a biographical profile of the author of the treatise. Chapter Two focuses on the manuscript witnesses of the Kitāb nūr al-ʿuyūn wa-ǧāmiʿ al-funūn, which are thoroughly analyzed with regard to their codicological and paleographical characteristics. In Chapter Three, the critical edition and annotated translation of the second maqāla are provided. Three Appendices conclude the study. Appendix I is devoted to diagrams; synoptical tables comparing the lectiones of the lettering and the drawings of manuscripts are presented. Appendix II focuses on bāb 14 of the ninth maqāla, “On strabismus and its cure”; the critical edition of the Arabic text and an annotated translation are provided. Appendix III is a specialized glossary of technical terms relating to the field of optics. Finally, a bibliography is supplied
Efficacy of low-dose rituximab for mixed cryoglobulinemia
No full textRituximab at 375 mg/m(2) x 4 is effective for refractory HCV-related mixed cryoglobulinemia. We conducted a pilot study to assess the efficacy of a lower dosage, 250 mg/m(2) x 2. Six consecutive patients with mixed cryoglobutinemia were treated. All patients had severe or life-threatening disease manifestations, including necrotizing skin ulcers, renal disease, hyperviscosity or intestinal vasculitis. Four of five evaluable patients (excluding one early death) had > 80% decrease of cryocrit and remission of vasculitis at the end of a 22- to 55-week (median 40) follow-up. The non-responder failed to respond to additional rituximab treatment, suggesting intrinsic resistance rather than insufficient dosage as the cause of treatment failure. No sustained increase of HCV viremia after rituximab was observed. Rituximab at 250 mg/m(2) X 2 may be as effective as at 375 mg/m(2) x 4 for treating mixed cryoglobulinemia. Larger studies are required to assess the efficacy of low-dose rituximab. (c) 2007 Elsevier Inc. All rights reserved
How Human Papillomavirus Replication and Immune Evasion Strategies Take Advantage of the Host DNA Damage Repair Machinery
No full textThe DNA damage response (DDR) is a complex signalling network activated when DNA is altered by intrinsic or extrinsic agents. DDR plays important roles in genome stability and cell cycle regulation, as well as in tumour transformation. Viruses have evolved successful life cycle strategies in order to ensure a chronic persistence in the host, virtually avoiding systemic sequelae and death. This process promotes the periodic shedding of large amounts of infectious particles to maintain a virus reservoir in individual hosts, while allowing virus spreading within the community. To achieve such a successful lifestyle, the human papilloma virus (HPV) needs to escape the host defence systems. The key to understanding how this is achieved is in the virus replication process that provides by itself an evasion mechanism by inhibiting and delaying the host immune response against the viral infection. Numerous studies have demonstrated that HPV exploits both the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and rad3-related (ATR) DDR pathways to replicate its genome and maintain a persistent infection by downregulating the innate and cell-mediated immunity. This review outlines how HPV interacts with the ATM- and ATR-dependent DDR machinery during the viral life cycle to create an environment favourable to viral replication, and how the interaction with the signal transducers and activators of transcription (STAT) protein family and the deregulation of the Janus kinase (JAK)–STAT pathways may impact the expression of interferon-inducible genes and the innate immune responses
Staphylococcus aureus colonizing the skin microbiota of adults with severe atopic dermatitis exhibits genomic diversity and convergence in biofilm traits
No full textAtopic dermatitis (AD) is a chronic inflammatory skin disorder exacerbated by Staphylococcus aureus colonization. The specific factors that drive S. aureus overgrowth and persistence in AD remain poorly understood. This study analyzed skin barrier functions and microbiome diversity in lesional (LE) and non-lesional (NL) forearm sites of individuals with severe AD compared to healthy control subjects (HS). Notable differences were found in transepidermal water loss, stratum corneum hydration, and microbiome composition. Cutibacterium was more prevalent in HS, while S. aureus and S. lugdunensis were predominantly found in AD LE skin. The results highlighted that microbial balance depends on inter-species competition. Specifically, network analysis at the genus level demonstrated that overall bacterial correlations were higher in HS, indicating a more stable microbial community. Notably, network analysis at the species level revealed that S. aureus engaged in competitive interactions in NL and LE but not in HS. Whole-genome sequencing (WGS) showed considerable genetic diversity among S. aureus strains from AD. Despite this variability, the isolates exhibited convergence in key phenotypic traits such as adhesion and biofilm formation, which are crucial for microbial persistence. These common phenotypes suggest an adaptive evolution, driven by competition in the AD skin microenvironment, of S. aureus and underscoring the interplay between genetic diversity and phenotypic convergence in microbial adaptation
Development of Approaches and Metrics to Measure the Impact and Improve the Clinical Outcomes of Patients With Frailty in the Era of COVID-19. The COMETA Italian Protocol
No full textThe outbreak of the coronavirus 2 disease 2019 (COVID-19) puts an enormous burden on healthcare systems worldwide. This may worsen outcomes in patients with severe chronic diseases such as cancer, autoimmune diseases, and immune deficiencies. In this critical situation, only a few available data exist, which do not allow us to provide practical guides for the treatment of oncological or immunocompromised patients. Therefore, a further step forward is needed, addressing the specific needs and demands of frail patients in the pandemic era. Here we aim to present a protocol of a study approved by an ethical committee named “CO.M.E.TA”. CO.M.E.TA protocol is a network project involving six Italian institutions and its goals are: i) to measure and compare the impact of the pandemic on the access of cancer and immunocompromised patients to therapies in three Italian regions; ii) to assess how reorganizational measures put in place in these different institutions have impacted specific metrics of performance; iii) to establish a COVID-19 Biobank of biological samples from SARS-CoV-2 infected patients to be used to study immunological alterations in patients with immune frailty
Detection of recent HIV infections in African individuals infected by HIV-1 non-B subtypes using HIV antibody avidity
No full textBackground: To estimate HIV incidence several methods have been used to discriminate recent HIV infections from long-standing infections using a single serum sample. Objective: To evaluate the performance of the anti-HIV avidity index (AI) for identifying recent HIV infections in individuals with a known date of seroconversion from Uganda, where the predominant HIV subtypes are A and D. Study design: We selected 149 repository serum samples from Ugandan HIV-positive individuals and evaluated the AI. Specimens collected ≤6 months after seroconversion were considered as recent infections, and those collected >6 months as long-standing infections. All specimens were serotyped using a V3 peptide enzyme immunoassay. Results: The mean AI was 0.55 ± 0.21 among the 108 patients with recent infections and 0.93 ± 0.14 among the 41 samples from long-standing infections (p < 0.0001). The AI test showed a sensitivity of 85.2% and a specificity of 85.4% at a cutoff of 0.80. No significant association was observed between serotype and the misclassification of samples by AI. Conclusions: The AI, which is inexpensive and easy-to-perform, can be useful in identifying recent HIV infections in countries where HIV-1 non-B subtypes are prevalent. © 2007 Elsevier B.V. All rights reserved
It is time to improve the diagnostic workup of oropharyngeal cancer with circulating tumor HPV DNA: systematic review and meta‐analysis
No full textAbstractThe possibility of detecting circulating tumor HPV DNA (ctHPVDNA) in plasma in patients with oropharyngeal cancer has been demonstrated in several reports. However, these data are from small cohorts and available tests for detection of ctHPVDNA are not fully validated. The aim is to evaluate sensitivity, specificity, and accuracy of ctHPVDNA by ddPCR to define its efficacy in the clinical setting for the diagnosis of HPV + OPSCC. A comprehensive search of three different databases: MEDLINE, Embase, and Cochrane Library databases. A total of 998 patients were evaluated from the 13 studies. OPSSC p16+ were 729, while controls p16− were 269. The meta‐analytic study estimated the diagnostic performance of ctHPVDNA as follows: pooled sensitivity and specificity of 0.90 (95% CI: 0.82–0.94) and 0.94 (95% CI: 0.85–0.98), respectively; positive and negative likelihood ratios of 12.6 (95% CI: 4.9–32.1) and 0.05 (95% CI: 0.02–0.13), respectively. ddPCR for ctHPVDNA has good accuracy, sensitivity, and specificity for diagnosis of HPV + OPSCC. ctHPVDNA kinetic represents a great reliable opportunity to improve diagnostic and therapeutic management of cancer patients and could open new perspectives for understanding tumor biology
Development of an in vitro Assay, Based on the BioFilm Ring Test®, for Rapid Profiling of Biofilm-Growing Bacteria
No full textMicrobial biofilm represents a major virulence factor associated with chronic and recurrent infections. Pathogenic bacteria embedded in biofilms are highly resistant to environmental and chemical agents, including antibiotics and therefore difficult to eradicate. Thus, reliable tests to assess biofilm formation by bacterial strains as well as the impact of chemicals or antibiotics on biofilm formation represent desirable tools for a most effective therapeutic management and microbiological risk control. Current methods to evaluate biofilm formation are usually time-consuming, costly, and hardly applicable in the clinical setting.The aim of the present study was to develop and assess a simple and reliable in vitro procedure for the characterization of biofilm-producing bacterial strains for future clinical applications based on the BioFilm Ring Test® (BRT) technology. The procedure developed for clinical testing (cBRT) can provide an accurate and timely (5 hours) measurement of biofilm formation for the most common pathogenic bacteria seen in clinical practice. The results gathered by the cBRT assay were in agreement with the traditional crystal violet (CV) staining test, according to the kappa coefficient test (kappa = 0.623). However, the cBRT assay showed higher levels of specificity (92.2%) and accuracy (88.1%) as compared to CV. The results indicate that this procedure offers an easy, rapid and robust assay to test microbial biofilm and a promising tool for clinical microbiology
Efficacy of sodium hypochlorite in overcoming antimicrobial resistance and eradicating biofilms in clinical pathogens from pressure ulcers
No full textSodium hypochlorite (NaOCl) is widely recognized for its broad-spectrum antimicrobial efficacy in skin wound care. This study investigates the effectiveness of NaOCl against a range of bacterial and fungal isolates from pressure ulcer (PU) patients.We analyzed 20 bacterial isolates from PU patients, comprising carbapenem-resistant Klebsiella pneumoniae (CRKP), multidrug-resistant Acinetobacter baumannii (MDRAB), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), along with 5 Candida albicans isolates. Antibiotic resistance profiles were determined using standard susceptibility testing. Whole-genome sequencing (WGS) was employed to identify antimicrobial resistance genes (ARGs) and disinfectant resistance genes (DRGs). Genetic determinants of biofilm formation were also assessed. The antimicrobial activity of NaOCl was evaluated by determining the minimum inhibitory concentration (MIC) and the minimal biofilm eradication concentration (MBEC) for both planktonic and biofilm-associated cells.CRKP and MDRAB showed resistance to fluoroquinolones and carbapenems, while MRSA exhibited resistance to β-lactams and levofloxacin. MSSA displayed a comparatively lower resistance profile. WGS identified significant numbers of ARGs in CRKP and MDRAB, with fewer DRGs compared to MRSA and MSSA. All isolates possessed genes associated with fimbriae production and adhesion, correlating with pronounced biofilm biomass production. NaOCl demonstrated substantial antimicrobial activity against both planktonic cells and biofilms. The MIC90 for planktonic bacterial cells was 0.125 mg/mL, and the MBEC90 ranged from 0.225 to 0.5 mg/mL. For planktonic C. albicans, the MIC90 was 0.150 mg/mL, and the MBEC90 was 0.250 mg/mL.These results highlight the challenge in treating biofilm-associated infections and underscore the potential of NaOCl as a robust antimicrobial agent against difficult-to-treat biofilm infections at concentrations lower than those typically found in commercial disinfectants
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