Human Wounds and Its Burden: An Updated Compendium of Estimates

Significance: A 2018 retrospective analysis of Medicare beneficiaries identified that ∼8.2 million people had wounds with or without infections. Medicare cost estimates for acute and chronic wound treatments ranged from $28.1 billion to$96.8 billion. Highest expenses were for surgical wounds followed by diabetic foot ulcers, with a higher trend toward costs associated with outpatient wound care compared with inpatient. Increasing costs of health care, an aging population, recognition of difficult-to-treat infection threats such as biofilms, and the continued threat of diabetes and obesity worldwide make chronic wounds a substantial clinical, social, and economic challenge. Recent Advances: Chronic wounds are not a problem in an otherwise healthy population. Underlying conditions ranging from malnutrition, to stress, to metabolic syndrome, predispose patients to chronic, nonhealing wounds. From an economic point of view, the annual wound care products market is expected to reach $15–22 billion by 2024. The National Institutes of Health's (NIH) Research Portfolio Online Reporting Tool (RePORT) now lists wounds as a category. Future Directions: A continued rise in the economic, clinical, and social impact of wounds warrants a more structured approach and proportionate investment in wound care, education, and related research

Is Low Alveolar Type II Cell SOD3 in the Lungs of Elderly Linked to the Observed Severity of COVID-19?

Human lungs single cell RNA sequencing data from healthy donors (elderly and young; GEO accession number GSE122960) were analyzed to isolate and specifically study gene expression in alveolar type II cells. Co-localization of ACE2 and TMPRSS2 enables SARS-CoV 2 to enter the cells. Expression of these genes in the alveolar type II cells of elderly and young patients were comparable and therefore do not seem to be responsible for worse outcomes observed in COVID-19 affected elderly. In cells from the elderly, 263 genes were downregulated and 95 upregulated. SOD3 was identified as the top-ranked gene that was most down-regulated in the elderly. Other redox-active genes that were also downregulated in cells from the elderly included ATF4 and M2TA. ATF4, an ER stress sensor that defends lungs via induction of heme oxygenase 1. The study of downstream factors known to be induced by ATF4, according to Ingenuity Pathway AnalysisTM, identified 24 candidates. Twenty-one of these were significantly downregulated in the cells from the elderly. These downregulated candidates were subjected to enrichment using the Reactome Database identifying that in the elderly, the ability to respond to heme deficiency and the ATF4-dependent ability to respond to endoplasmic reticulum stress is significantly compromised. SOD3-based therapeutic strategies have provided beneficial results in treating lung disorders including fibrosis. The findings of this work propose the hypotheses that lung-specific delivery of SOD3/ATF4 related antioxidants may work in synergy with promising anti-viral drugs such as remdesivir to further improve COVID-19 outcomes in the elderly

Optimal Conflict in Team-Based Laboratory Culture

One critical determinant of success that is not part of standardized scientific training programs is the development of the right mindset for competitive team science. Mindset has been categorized as fixed and growth. People with fixed mindset who believe that virtues such as goodness and intelligence are naturally endowed and thus fixed are reportedly less likely to succeed than people with growth mindset who believe that such abilities are malleable and scalable. People with growth mindset handle conflicts more effectively. As it stands in academic culture, mostly dominated by the education mission, conflict is a taboo. Administrators generally view conflict as something that must be avoided or resolved. Yet the American Psychological Association, among many others, recognize that good science requires good conflict. Team science efforts must recognize the perils of artificial harmony. Artificial harmony is a state wherein members of the team act as if they are getting along in a setting where serious issues remain unattended. Artificial harmony stifles open communication. Open communication within the team is essential to uphold rigor in science. The threat of conflict triggers the flight or fight response in us. Flight, motivated by conflict avoidance, favors artificial harmony. Fight, in its optimal form, empowers teammates to express their opinion leading to healthy disagreement and debate. Teams must find their own optimal conflict point. Mastering that art of identifying and achieving the optimal conflict point for any given team will return lucrative dividends in the form of competitive edge

Residual Limb Health and Prosthetics

The residual limb of individuals with lower limb loss is dynamic tissue that is susceptible to both acute and chronic changes to limb volume and health over time. Changes in residual limb volume that affect socket fit may contribute to maladaptive gait patterns and deleterious changes to the socket/limb interface that increase harmful shear stress and contributes to residual limb skin injury. Current socket systems are static and lack the ability to provide end-users and prosthetists with patient-centric data about changes in socket fit over time. There is a need for objective clinical decision-making that results in greater prosthesis usage, improved residual limb health, and better comfort ratings for end-users. Among the socket systems available in the market, the elevated vacuum suspension system improves residual limb skin oxygenation, attenuates socket-induced reactive hyperemia and preserves skin barrier function. This suggests that such a system is compatible with imparting physiological benefits to the residual limb in people with lower limb amputations

Sociogenomic Approach to Wound Care: A New Patient-Centered Paradigm

Psychoneuroendocrinology studies provided first insight into social determinants of wound healing. Social stressors impede wound healing. In 2005, we first reported that the transcriptome of wound-site neutrophil is highly responsive to psychological stress in young men. Bioinformatics processing of transcriptome-wide data from neutrophils provided first insight into social transduction pathways relevant to wound healing. In 2010, Idaghdour et al. presented striking evidence demonstrating that genetic factors are responsible for only 5% of the variation in genomic expression. In contrast, the living environment of the individual, urban or rural, was responsible for as much as 50% of such variation. Genetic and environmental factors acted in a largely additive manner. This observation may be credited as the foundation stone of human social genomics. The environment of a patient, including social factors, influences gene expression relevant to wound healing. The nonhealing wound itself and its worsening outcome, including pain, are likely to cause stress. Conversely, positive social interactions may circumvent barriers to wound healing. Thus, interventions directed at the social environment of a wound care patient are likely to help manage wound chronicity. The genomic and related Big Data technology platforms have vastly improved during the past 5 years during which these technologies have also become widely accessible and affordable. Thus, this is the right time to revisit the choice of technologies for the study of social genomics of wound healing. Against the backdrop of our current understanding of the mechanisms of wound healing, such precision approach is likely to transform wound care and its outcomes making it patient-centered and, therefore, more effective

Vitamin E sensitive genes in the developing rat fetal brain: a high-density oligonucleotide microarray analysis

AbstractVitamin E (tocopherols and tocotrienols) is essential for normal neurological function. Recently we have reported that the neuroprotective properties of tocotrienols are much more potent than that of the widely studied tocopherols (Sen, C.K., Khanna, S., Roy, S. and Parker, L. (2000) J. Biol. Chem. 275, 13049–13055). The objective of this study was to evaluate whether (i) oral supplementation of tocotrienols during pregnancy is bioavailable to fetal and mother brains; (ii) short-term change in dietary vitamin E levels of pregnant rats influences gene expression profile of developing fetal brains. We report that dietary tocotrienol is bioavailable to both mother and fetal brains. The enrichment is more in fetal brain tissue. Using a GeneChip microarray expression profiling approach we have identified a specific set of vitamin E sensitive genes in the developing rat fetal brain

Cutaneous Manifestations of COVID-19: A Systematic Review

Objective: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a pandemic. Although pulmonary health has been the primary focus of studies during the early days of COVID-19, development of a comprehensive understanding of this emergent disease requires knowledge of all possible disease manifestations in affected patients. This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant review focuses on cutaneous manifestations reported in COVID-19 patients. Approach: Literature review was conducted using the PubMed database to examine various cutaneous manifestations related to the SARS-CoV-2 infection. Published articles (n = 56) related to search criteria from the onset of the COVID-19 pandemic to June 30, 2020, were included. The primary literature articles included in this study were mainly from France, Spain, Italy, and the United Kingdom. Results: Unique to many other symptoms of COVID-19, its cutaneous manifestations have been found in people of all age groups, including children. The cutaneous manifestations of COVID-19 are varied and include maculopapular, chilblain-like, urticarial, vesicular, livedoid, and petechial lesions. In addition, rashes are common in multisystem inflammatory syndrome in children, a new and serious health condition that shares symptoms with Kawasaki disease and is likely related to COVID-19. In addition, personal protective equipment-related skin wounds are of serious concern since broken cutaneous barriers can create an opening for potential COVID-19 infections. Innovation and Conclusion: As this virus continues to spread silently, mainly through asymptomatic carriers, an accurate and rapid identification of these cutaneous manifestations may be vital to early diagnosis and lead to possible better prognosis in COVID-19 patients. This systematic review and photo atlas provide a detailed analysis of the skin pathologies related to COVID-19. Study of these cutaneous manifestations and their pathogenesis, as well their significance in human health will help define COVID-19 in its entirety, which is a prerequisite to its effective management

Collagen in Wound Healing

Normal wound healing progresses through inflammatory, proliferative and remodeling phases in response to tissue injury. Collagen, a key component of the extracellular matrix, plays critical roles in the regulation of the phases of wound healing either in its native, fibrillar conformation or as soluble components in the wound milieu. Impairments in any of these phases stall the wound in a chronic, non-healing state that typically requires some form of intervention to guide the process back to completion. Key factors in the hostile environment of a chronic wound are persistent inflammation, increased destruction of ECM components caused by elevated metalloproteinases and other enzymes and improper activation of soluble mediators of the wound healing process. Collagen, being central in the regulation of several of these processes, has been utilized as an adjunct wound therapy to promote healing. In this work the significance of collagen in different biological processes relevant to wound healing are reviewed and a summary of the current literature on the use of collagen-based products in wound care is provided

Platelet Function in Stroke/Transient Ischemic Attack Patients Treated with Tocotrienol

The purpose of this study was to characterize the effects of tocotrienol form of vitamin E (TCT) on platelet function in patients with stroke or transient ischemic attack (TIA). A double blind, randomized, single center phase II clinical trial was conducted comparing placebo (PBO) and 400 and 800 mg TCT daily for a year in 150 patients with a sentinel ischemic stroke or TIA event in the prior 6 months. Platelet function was measured at baseline and then, at 3 month intervals for a year, using light transmission aggregometry. The incidence of aspirin resistance in aspirin-treated patients or platelet inhibition in patients on clopidogrel alone was compared between the three treatment groups. Results showed that in patients taking aspirin and clopidogrel, the incidence of aspirin resistance was significantly decreased from 40% in PBO-treated patients to 9% in the 400 mg TCT group and 25% in the TCT 800 mg group (P = .03). In conclusion, patients on aspirin and clopidogrel had a higher incidence of aspirin resistance than all patients treated with aspirin alone and TCT decreased the frequency of aspirin resistance in this group

Novel Bacterial Diversity and Fragmented eDNA Identified in Hyperbiofilm-Forming Pseudomonas aeruginosa Rugose Small Colony Variant

Pseudomonas aeruginosa biofilms represent a major threat to health care. Rugose small colony variants (RSCV) of P. aeruginosa, isolated from chronic infections, display hyperbiofilm phenotype. RSCV biofilms are highly resistant to antibiotics and host defenses. This work shows that RSCV biofilm aggregates consist of two distinct bacterial subpopulations that are uniquely organized displaying contrasting physiological characteristics. Compared with that of PAO1, the extracellular polymeric substance of RSCV PAO1ΔwspF biofilms presented unique ultrastructural characteristics. Unlike PAO1, PAO1ΔwspF released fragmented extracellular DNA (eDNA) from live cells. Fragmented eDNA, thus released, was responsible for resistance of PAO1ΔwspF biofilm to disruption by DNaseI. When added to PAO1, such fragmented eDNA enhanced biofilm formation. Disruption of PAO1ΔwspF biofilm was achieved by aurine tricarboxylic acid, an inhibitor of DNA-protein interaction. This work provides critical novel insights into the contrasting structural and functional characteristics of a hyperbiofilm-forming clinical bacterial variant relative to its own wild-type strain