ABSTRACT
The application of antimicrobials in the management of wounds is a complex procedure requiring appropriate clinical decision making, judgment and a thorough understanding of antimicrobial ...therapies, together with their potential disadvantages. There is considerable direct and indirect evidence for the presence of bacterial biofilms in the chronic wound bed, and it has been demonstrated that bacteria within these biofilms may exhibit both specific and nonspecific antimicrobial tolerance. The antimicrobial tolerance of biofilms is a major concern in the treatment of both infected and nonhealing chronic wounds and an understanding of the mechanisms involved is of fundamental importance in managing wound infections and developing future wound management strategies. The aim of this review is therefore to provide an overview of our current understanding of the mechanisms by which bacteria in wound biofilms can resist conventional antibiotic and antibacterial therapies which is very important to wound healing.
Both chronic and acute dermal wounds are susceptible to infection due to sterile loss of the innate barrier function of the skin and dermal appendages, facilitating the development of microbial ...communities, referred to as biofilms, within the wound environment. Microbial biofilms are implicated in both the infection of wounds and failure of those wounds to heal. The aim of this review is to provide a summary of published papers detailing biofilms in wounds, the effect they have on infection and wound healing, and detailing methods employed for their detection. The studies highlighted within this paper provide evidence that biofilms reside within the chronic wound and represent an important mechanism underlying the observed, delayed healing and infection. The reasons for this include both protease activity and immunological suppression. Furthermore, a lack of responsiveness to an array of antimicrobial agents has been due to the biofilms’ ability to inherently resist antimicrobial agents. It is imperative that effective strategies are developed, tested prospectively, and employed in chronic wounds to support the healing process and to reduce infection rates. It is increasingly apparent that adoption of a biofilm‐based management approach to wound care, utilizing the “antibiofilm tool box” of therapies, to kill and prevent reattachment of microorganisms in the biofilm is producing the most positive clinical outcomes and prevention of infection.
Extant research suggests that entrepreneurs’ identities influence the venture creation process. However, we know little about how the “hats” that entrepreneurs wear (i.e., their different role ...identities) influence how entrepreneurs think about—and select—opportunities. Employing verbal protocol and content analysis techniques, we show that, depending on the role identity assumed, entrepreneurs attend to different opportunity features and make different decisions with regard to opportunity consideration and selection. As a result, role identity has an important situated influence on entrepreneurs’ cognition, which may significantly affect the pattern of growth and pursuit of their new ventures.
The spinal dorsal horn is a major site for the induction and maintenance of mechanical allodynia, but the circuitry that underlies this clinically important form of pain remains unclear. The studies ...presented here provide strong evidence that the neural circuits conveying mechanical allodynia in the dorsal horn differ by the nature of the injury. Calretinin (CR) neurons in lamina II inner convey mechanical allodynia induced by inflammatory injuries, while protein kinase C gamma (PKCγ) neurons at the lamina II/III border convey mechanical allodynia induced by neuropathic injuries. Cholecystokinin (CCK) neurons located deeper within the dorsal horn (laminae III–IV) are important for both types of injuries. Interestingly, the Maf+ subset of CCK neurons is composed of transient vesicular glutamate transporter 3 (tVGLUT3) neurons, which convey primarily dynamic allodynia. Identification of an etiology-based circuitry for mechanical allodynia in the dorsal horn has important implications for the mechanistic and clinical understanding of this condition.
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•CR neurons are important for mechanical allodynia in inflammatory injuries•PKCγ neurons are important for mechanical allodynia in neuropathic injuries•CCK and tVGLUT3 neurons in deeper laminae convey both types of injuries•The Maf+ subset of CCK neurons encompasses tVGLUT3 and conveys dynamic allodynia
Peirs et al. identified distinct spinal cord microcircuits that underlie mechanical allodynia, depending on the injury type. The neurons engaged after neuropathic or inflammatory injuries include populations that express CCK, tVGLUT3, CR, and PKCγ.
Abstract
The incidence of infections caused by Candida species (candidosis) has increased considerably over the past three decades, mainly due to the rise of the AIDS epidemic, an increasingly aged ...population, higher numbers of immunocompromised patients and the more widespread use of indwelling medical devices. Candida albicans is the main cause of candidosis; however, non-C. albicans Candida (NCAC) species such as Candida glabrata, Candida tropicalis and Candida parapsilosis are now frequently identified as human pathogens. The apparent increased emergence of these species as human pathogens can be attributed to improved identification methods and also associated with the degree of diseases of the patients, the interventions that they were subjected and the drugs used. Candida pathogenicity is facilitated by a number of virulence factors, most importantly adherence to host surfaces including medical devices, biofilm formation and secretion of hydrolytic enzymes (e.g. proteases, phospholipases and haemolysins). Furthermore, despite extensive research to identify pathogenic factors in fungi, particularly in C. albicans, relatively little is known about NCAC species. This review provides information on the current state of knowledge on the biology, identification, epidemiology, pathogenicity and antifungal resistance of C. glabrata, C. parapsilosis and C. tropicalis.
This review aims to gather the most relevant information regarding biology, identification, epidemiology, pathogenicity and antifungal resistance of C. glabrata, C. parapsilosis and C. tropicalis.
The purpose of this study is to compare real-world visual acuity (VA) in patients with neovascular age-related macular degeneration (nAMD) treated with a single anti-vascular endothelial growth ...factor (VEGF) drug monotherapy for 1 year from the American Academy of Ophthalmology (AAO) Intelligent Research in Sight (IRIS) Registry.
Retrospective, nonrandomized, comparative study.
IRIS Registry patients with nAMD who received bevacizumab, ranibizumab, or aflibercept only for 1 year between 2013-2016.
Participants were divided into 3 groups based on monotherapy type. Multivariate analysis of covariance models (ANCOVA) was constructed in a stepwise fashion.
The logarithm of the minimum angle of resolution (logMAR) VA at 1 year and mean change in logMAR VA between baseline and 1 year were compared between drug types.
Of 13 859 patients, 6723 received bevacizumab, 2749 received ranibizumab, and 4387 received aflibercept only for 1 year. A total of 84 828 injections were performed. The mean number of injections (standard deviation) at 1 year was higher in the ranibizumab (6.4 ±2.4) and aflibercept groups (6.2 ±2.4) compared to bevacizumab group (5.9 ±2.4; P < 0.0001). In the age-adjusted model, both ranibizumab and aflibercept achieved better logMAR VA at 1 year compared with bevacizumab (0.50 ±0.49, 0.49 ±0.44, 0.55 ±0.57; P < 0.0001). However, this difference was not significant after multivariate adjustment (age, baseline VA, diabetes, posterior vitreous detachment, number of injections, race, insurance). There was no statistical difference in the age-adjusted or multivariate-adjusted mean logMAR VA change (standard deviation) at 1 year among treatment groups (-0.048 0.44 bevacizumab, -0.053 0.46 ranibizumab, -0.040 0.39 aflibercept; P = 0.46). A higher percentage of patients achieved a ≥3-line VA improvement at 1 year in the bevacizumab group (22.7%) compared with ranibizumab (20.1%; P = 0.0093) and aflibercept (17.8%; P < 0.0001). However, after multivariate adjustment, aflibercept exhibited a greater log odds of a ≥3-line VA loss compared with bevacizumab only (1.25 log odds ratio; P < 0.0016).
This study suggests that all 3 drugs improve VA similarly over 1 year of monotherapy.
Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC) programmed cell death (apoptosis) that may ...contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF) and asbestosis (pulmonary fibrosis following asbestos exposure). The mammalian mitochondrial DNA (mtDNA) encodes for 13 proteins, including several essential for oxidative phosphorylation. We review the evidence implicating that oxidative stress-induced mtDNA damage promotes AEC apoptosis and pulmonary fibrosis. We focus on the emerging role for AEC mtDNA damage repair by 8-oxoguanine DNA glycosylase (OGG1) and mitochondrial aconitase (ACO-2) in maintaining mtDNA integrity which is important in preventing AEC apoptosis and asbestos-induced pulmonary fibrosis in a murine model. We then review recent studies linking the sirtuin (SIRT) family members, especially SIRT3, to mitochondrial integrity and mtDNA damage repair and aging. We present a conceptual model of how SIRTs modulate reactive oxygen species (ROS)-driven mitochondrial metabolism that may be important for their tumor suppressor function. The emerging insights into the pathobiology underlying AEC mtDNA damage and apoptosis is suggesting novel therapeutic targets that may prove useful for the management of age-related diseases, including pulmonary fibrosis and lung cancer.
Abstract
Mouse lemurs (Microcebus) are a radiation of morphologically cryptic primates distributed throughout Madagascar for which the number of recognized species has exploded in the past two ...decades. This taxonomic revision has prompted understandable concern that there has been substantial oversplitting in the mouse lemur clade. Here, we investigate mouse lemur diversity in a region in northeastern Madagascar with high levels of microendemism and predicted habitat loss. We analyzed RADseq data with multispecies coalescent (MSC) species delimitation methods for two pairs of sister lineages that include three named species and an undescribed lineage previously identified to have divergent mtDNA. Marked differences in effective population sizes, levels of gene flow, patterns of isolation-by-distance, and species delimitation results were found among the two pairs of lineages. Whereas all tests support the recognition of the presently undescribed lineage as a separate species, the species-level distinction of two previously described species, M. mittermeieri and M. lehilahytsara is not supported—a result that is particularly striking when using the genealogical discordance index (gdi). Nonsister lineages occur sympatrically in two of the localities sampled for this study, despite an estimated divergence time of less than 1 Ma. This suggests rapid evolution of reproductive isolation in the focal lineages and in the mouse lemur clade generally. The divergence time estimates reported here are based on the MSC calibrated with pedigree-based mutation rates and are considerably more recent than previously published fossil-calibrated relaxed-clock estimates. We discuss the possible explanations for this discrepancy, noting that there are theoretical justifications for preferring the MSC estimates in this case. Cryptic species; effective population size; microendemism; multispecies coalescent; speciation; species delimitation.
Background:
There is increased interest in understanding the preoperative determinants of postoperative outcomes. Return to play (RTP) and the patient-reported minimal clinically important difference ...(MCID) are useful measures of postoperative outcomes after anterior cruciate ligament reconstruction (ACLR).
Purpose:
To define the MCID after ACLR and to investigate the role of preoperative outcome scores for predicting the MCID and RTP after ACLR.
Study Design:
Case-control study; Level of evidence, 3.
Methods:
There were 294 active athletes enrolled as part of an institutional ACL registry with a minimum 2-year follow-up who were eligible for inclusion. A questionnaire was administered to elicit factors associated with RTP. Patient demographic and clinical data as well as patient-reported outcome measures were captured as part of the registry. Outcome measures included the International Knee Documentation Committee (IKDC) subjective knee evaluation form, Lysholm scale, and 12-Item Short Form Health Survey (SF-12) physical component summary (PCS) and mental component summary (MCS). Preoperative outcome score thresholds predictive of RTP were determined using a receiver operating characteristic (ROC) with area under the curve (AUC) analysis. The MCID was calculated using a distribution-based method. Multivariable logistic models were fitted to identify predictors for achieving the MCID and RTP.
Results:
At a mean (±SD) follow-up of 3.7 ± 0.7 years, 231 patients were included from a total 294 eligible patients. The mean age and body mass index were 26.7 ± 12.5 years and 23.7 ± 3.2 kg/m2, respectively. Of the 231 patients, 201 (87.0%) returned to play at a mean time of 10.1 months. Two-year postoperative scores on all measures were significantly increased from preoperative scores (IKDC: 50.1 ± 15.6 to 87.4 ± 10.7; Lysholm: 61.2 ± 18.1 to 89.5 ± 10.4; SF-12 PCS: 41.5 ± 9.0 to 54.7 ± 4.6; SF-12 MCS: 53.6 ± 8.1 to 55.7 ± 5.7; P < .001 for all). The corresponding MCID values were 9.0 (IKDC), 10.0 (Lysholm), 5.1 (SF-12 PCS), and 4.3 (SF-12 MCS). Preoperative score thresholds predictive of RTP were the following: IKDC, 60.9; Lysholm, 57.0; SF-12 PCS, 42.3; and SF-12 MCS, 48.3. These thresholds were not independently predictive but achieved significance as part of the multivariable analysis. In the multivariable analysis for RTP, preoperative SF-12 PCS scores above 42.3 (odds ratio OR, 2.73; 95% CI, 1.09-7.62) and SF-12 MCS scores above 48.3 (OR, 4.41; 95% CI, 1.80-10.98) were predictive for achieving RTP; an ACL allograft (OR, 0.26; 95% CI, 0.06-1.00) was negatively predictive of RTP. In the multivariable analysis for the MCID, patients with higher preoperative scores were less likely to achieve the MCID (P < .0001); however, a higher preoperative SF-12 MCS score was predictive of achieving the MCID on the IKDC form (OR, 1.27; 95% CI, 1.11-1.52) and Lysholm scale (OR, 1.08; 95% CI, 1.00-1.16). Medial meniscal injuries, older age, and white race were also associated with a decreased likelihood for achieving the MCID.
Conclusion:
Preoperative SF-12 MCS and PCS scores were predictive of RTP after ACLR; patients scoring above 42.3 on the SF-12 PCS and 48.3 on the SF-12 MCS were more likely to achieve RTP. Additionally, we defined the MCID after ACLR and found that higher SF-12 MCS scores were predictive of achieving the MCID on knee-specific questionnaires.
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