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

Descriptive study of outcome of antibiotic cement-impregnated intramedullary nail in treatment of infected non-union of weight bearing long bones

Background: Infected non-union of tibia and femur is a debilitating disorder for patient as well as challenging task for treating surgeon. Conventionally treatment of infected non-union is a two staged procedure. But antibiotic cement-impregnated intramedullary nailing (ACIINs) is a single staged and cost-effective procedure. Hence we intended to study the outcome of ACIIN use in infected non-union of tibia and femur.Methods: This is a hospital based prospective case series type of descriptive study conducted in Department of Orthopedics, SMS Medical College and Hospital, Jaipur. We studied 35 cases of infected non-union of femur and tibia fracture with interlock nail in situ. All patients were treated with interlock nail removal, debridement and freshening of sclerosed bony ends and fixation with ACIIN. All were followed for at least 6 months for infection control and bony union and final results were evaluated by Paley’s bony criteria and functional criteria.Results: Infection was controlled in 94.28% cases. Bony union was achieved in 88.57% cases (19 femur and 12 tibia). Average duration for bony union was 7.3 months for femur and 8 months for tibia. According to Paley’s criteria for bony outcome and functional outcome 65.71% and 51.43% had shown excellent outcome respectively.Conclusions: ACIIN is a good modality for treatment of infected non union of tibia and femur in terms of infection control and bony union and has a good functional outcome when bone gap is less

Outcome analysis of surgical management of comminuted quadrilateral plate acetabulum fractures

Background: The acetabular quadrilateral fractures are difficult to treat and ORIF using a spring plate buttressing the quadrilateral surface underneath an iliopectenial plate in a 90-90 construct. The aim of the study was to assess the clinical and radiological outcome, success rate and proportion of the post-operative complications of surgical management of comminuted quadrilateral plate acetabulum fractures after ORIF.Methods: It was a hospital based descriptive type of observational study conducted in the Department of Orthopedics, SMS Medical College. The data collection was done from May 2016 up to June 2018. The sample size was 31 for the study purpose, at 95% confidence limits and 20% relative allowable error.Results: We studied 31 patients of communited quadrilateral plate fractures, who were evaluated preoperatively and optimized. ORIF was performed. The mean blood loss was 450 ml and the mean operating time was 130 minutes. The patients were followed up at 1 year postoperatively where 24 patients had an excellent to good Harris Hip clinical score and 24 patients had an excellent to good Matta radiological score, and both were found to be statistically significant.Conclusions: Comminuted quadrilateral plate fractures of the acetabulum are managed surgically by ORIF using a spring buttressing plate beneath the infrapectenial plate. The clinical and radiological follow up for one year duration scores showed good scores which were statistically significant, indicating the success of quadrilateral fixation using this technique.

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

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

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

Nutrigenomic Analysis of Diet-Gene Interactions on Functional Supplements for Weight Management

Recent advances in molecular biology combined with the wealth of information generated by the Human Genome Project have fostered the emergence of nutrigenomics, a new discipline in the field of nutritional research. Nutrigenomics may provide the strategies for the development of safe and effective dietary interventions against the obesity epidemic. According to the World Health Organization, more than 60% of the global disease burden will be attributed to chronic disorders associated with obesity by 2020. Meanwhile in the US, the prevalence of obesity has doubled in adults and tripled in children during the past three decades. In this regard, a number of natural dietary supplements and micronutrients have been studied for their potential in weight management. Among these supplements, (–)-hydroxycitric acid (HCA), a natural extract isolated from the dried fruit rind of Garcinia cambogia, and the micronutrient niacin-bound chromium(III) (NBC) have been shown to be safe and efficacious for weight loss. Utilizing cDNA microarrays, we demonstrated for the first time that HCA-supplementation altered the expression of genes involved in lipolytic and adipogenic pathways in adipocytes from obese women and up-regulated the expression of serotonin receptor gene in the abdominal fat of rats. Similarly, we showed that NBC-supplementation up-regulated the expression of myogenic genes while suppressed the expression of genes that are highly expressed in brown adipose tissue in diabetic obese mice. The potential biological mechanisms underlying the observed beneficial effects of these supplements as elucidated by the state-of-the-art nutrigenomic technologies will be systematically discussed in this review