Ulcer Research Articles

Effective Management of Chronic Lower-Extremity Ulcers (CLEU) by Fu’s Subcutaneous Needling (FSN)

Effective Management of Chronic Lower-Extremity Ulcers (CLEU) by Fu’s Subcutaneous Needling (FSN)

Analysis of clinical characteristics and factors affecting treatment responses in patients with pyoderma gangrenosum: a multicenter study of 239 patients☆

BackgroundPyoderma Gangrenosum (PG) is a chronic disease characterized by recalcitrant skin ulcers. ObjectiveWe aimed to evaluate the demographic, clinical characteristics, treatments and factors affecting the treatment responses of patients with PG. MethodsWe performed a multicenter study of 12 tertiary care centers. We analyzed the data of the patients who were followed up with a diagnosis of PG between the years 2012‒2022 retrospectively. ResultsWe included a total of 239 patients of whom 143 were female and 96 were male, with an average age of 54.2 ± 17.4 years. The most common treatment was systemic steroids (n = 181, 75.7%). Among these patients, 50.8% (n = 92) used systemic steroids as the sole systemic agent, while 49.2% (n = 89) used at least one adjuvant immunosuppressive agent. The independent factors determined in regression analysis to influence response to systemic steroids positively were disease onset age ≥ 30-years, negative pathergy, absence of leukocytosis, negative wound culture, presence of a single lesion, and absence of upper extremity involvement. Biological agents were used in 18.4% (n = 44) of the patients in the present study. We also analyzed pathergy positive PG and early onset (onset age < 30) PG separately due to their distinct clinical features which were revealed during statistical analysis. Study limitationsRetrospective nature of the present study. ConclusionsAnalyses of the factors influencing treatment responses are addressed in this study. Also, we concluded that investigation for accompanying autoinflammatory diseases of pathergy positive PG and early onset PG is necessary and the patients in these two groups are more resistant to treatment, necessitating more complicated treatments.

The use of p-toluenesulfonic acid in the removal of biofilm in chronic ulcers

Background: Bacterial biofilms represent a topic of great concern due to their ability to cause chronic, sometimes fatal infections. Considering the prevalence and pathogenicity of biofilms in chronic ulcers, an observational study was designed to evaluate the anti-biofilm capabilities of p-toluenesulfonic acid, using it in the chronic ulcers of patients belonging to the Diabetic Foot clinic. Methods: Preliminary analysis of an observational study on patients attending the diabetic foot clinic with leg ulcers for at least 4 weeks. 17 patients treated with p-toluenesulfonic acid on a weekly basis for a maximum of 16 weeks. The primary outcome was 100% granulation tissue formation at week 16 and 50% reduction in initial chronic ulcer size. Results: The average treatment time was 10 ± 4.8 weeks. 8 patients healed, 7 are undergoing treatment, 1 required reoperation due to post-operative complications and 1 spontaneously dropped out of the study after 6 weeks. In the sample of healed patients, the average treatment time was 10.5 weeks with 100% granulation present at the 6th week. The reduction in the overall size of the ulcer and of the granulation area is not significant in the total sample. The data improves in the sample of healed patients even if it does not reach significance (lesion p-value 0.094, granulation p-value 0.13). Applying the analysis to the delta of the two variables, a measurement of the area that coincides with the margins of the ulcer, a p-value of 0.069 is obtained. The behaviour of the sample does not change when stratified by the dressings applied after treatment with p-toluenesulfonic acid. Conclusions: Treatment with p-toluenesulfonic acid promotes tissue granulation regardless of the type of dressing subsequently applied. The data on the evolution of the size of the lesions were not significant due to the smallness of the sample but in the sample of healed persons, the formation of granulation after an average of 6 applications transforms the "chronic" ulcer into an "active" ulcer, promoting closure within the subsequent 4 weeks. The appearance of granulation confirms healing. Elimination of biofilm with p-toluenesulfonic acid can reduce healing times and the risk of reinfection.

A Simplified Surgical Approach for Distal Clavicle Non-union and Concurrent Skin Ulceration in an Older Adult: A Case Report

A Simplified Surgical Approach for Distal Clavicle Non-union and Concurrent Skin Ulceration in an Older Adult: A Case Report

High glucose combined with lipopolysaccharide stimulation inhibits cell proliferation and migration of human HaCaT keratinocytes by impacting redox homeostasis and activating the polyol pathway.

High glucose level and chronic inflammation are characteristic features of diabetic cutaneous wounds. Keratinocytes make up the epidermis and play an important role in skin repair. However, metabolomic changes of keratinocytes in chronic diabetic ulcers have not been fully studied. This study used high levels of glucose combined with lipopolysaccharide to treat human HaCaT keratinocytes. Untargeted metabolomic combined with colorimetric assays were used to explore the changes of keratinocyte metabolites and related metabolic pathways caused by high glucose and lipopolysaccharide. Results demonstrated that high glucose combined with lipopolysaccharide treatment increased intracellular reactive oxygen species and impaired proliferation and migration of keratinocytes. Untargeted metabolomics analysis identified a total of 273 differential metabolites. Redox metabolism associated metabolites were largely altered. Reduced nicotinamide adenine dinucleotide, gamma-glutamylcysteine, superoxide dismutase activity and SOD2 gene expression were significantly upregulated while nicotinamide adenine dinucleotide, glutathione, glutathione peroxidase, several types of lysophosphatidylcholine, lysophosphatidylinositol, and GPR55 gene expression were downregulated. Alterations of glutathione and nicotinamide adenine dinucleotide were verified by colorimetric assays. For the first time, high glucose and LPS were observed to boost the levels of fructose, aldose reductase and sorbitol dehydrogenase of the polyol pathway in HaCaT cells. Further treatment of HaCaT with fructose leading to inhibition of cell proliferation and migration. Our data suggest high glucose combined with lipopolysaccharide significantly altered redox homeostasis associated metabolites and activate the polyol pathway in keratinocytes to impact cell proliferation and migration, providing new strategies for the treatment of chronic diabetic ulcers.

Histological Determination of Cinnamon and Olive Oil Extract on Traumatic Oral Ulcer in Laboratory Rabbit

Background: The mucosa of oral cavity is the mucous membrane which covers the tissues of the mouth cavity. In order to repair damage from a local aggressor, many cell strains and their byproducts work together throughout the vital physiological process of wound healing. This process culminates in tissue repair and starts relatively early in the inflammatory phase. . The supplements of cinnamon and olive oil can dramatically raise blood levels of antioxidants while lowering those of inflammatory indicators like C-reactive protein. Objective: The aim of the study was to determine the local histological effect of topical application of cinnamon and olive oil extract on the rabbit oral mucosa Patients and Methods: 20 adult male rabbits that weight about 700-900 Kg and age about (6-8) months where used in this experimental study. Ulcer induction: Prior to the creation of the ulcers, rats were fixed on their backs and all animals were anaesthetized and induction the ulcer with round filter papers 5.5 mm in diameter were soaked in 15 ml of 50% acetic acid. In order to create round ulcer, an acid-soaked filter paper was pressed onto the right buccal mucosa for 60 seconds. Then divided the groups according to the healing time with 10 rabbits as a control group left healed normally and 10 rabbits as an experimental group that daily used mixture of cinnamon extract and olive oil ready extract topically applied on the traumatic ulcer. The animals were sacrificed along three- and seven-days healing periods and then prepared H&amp;E stain for analyzed the results. Results: In comparison to the control group, the histological results of oral ulcers that were created and treated with a daily application of a herbal mixture consisting of cinnamon extract and olive oil extract showed greater epithelization, reduced inflammation, and increased angiogenesis, all of which sped up the healing process. Furthermore, there was a noteworthy distinction in the formation of extracellular matrix and collagen fiber synthesis between the experimental and control groups. Conclusion: Topical treatment using ready herbal extracts of olive oil and cinnamon was more successful in facilitating the recovery of traumatic ulcers.

Fabrication of a flexible inner prosthetic socket via the FGM technique

Purpose The purpose of this study was to fabricate a flexible inner socket with enhanced stiffness and hardness distribution by using the functional gradient method (FGM). The FGM technique can improve the comfort and flexibility of amputees through the use of a socket that is built via the direct method. Design/methodology/approach Six flexible inner socket samples were fabricated with varying weight fractions of rice husk ash-to-silicone rubber. The tensile strength and hardness of each sample were assessed. Then, numerical analyses were conducted using SOLIDWORKS software to evaluate the pressure distribution on the inner and outer layers of the flexible socket. Findings The hardness and stiffness of the fabricated flexible inner socket gradually increased with the weight ratio of rice husk ash-to-silicone rubber, so when it was in contact with the skin, it approximated the stiffness and hardness of the skin to ensure comfort, and when reaching a higher value in the socket contact layer, it prevented penetration through the flexible inner socket. In addition, the pressure distribution at the external layer of the flexible inner socket has improved. Research limitations/implications A budget of US$500 limited the research to create a flexible inner socket that keeps the socket from penetrating the skin. Practical implications The FGM technique created a flexible inner socket that balances hardness and stiffness to ensure comfort and prevent wounds for its users, lower limb amputees. The commercial value resides in the accessibility of a secure and comfortable flexible inner socket for amputees worldwide, enabling them to overcome the issue of excessive stiffness typically associated with sockets made using the direct method. Originality/value This study introduces the use of FGM to fabricate a flexible inner prosthetic socket with enhanced stiffness and hardness distribution. The approach of using varying weight fractions of rice husk ash-to-silicone rubber to improve the comfort and flexibility of prosthetic sockets is a novel contribution to the field. Given the high stiffness of flexible internal sockets and their ability to maintain flexibility in the part in contact with the skin, such sockets manufactured using this method prevent pain and skin ulcers that previously occurred when sockets are manufactured via the direct method.

Multi-drug resistant Staphylococcus epidermidis from chronic wounds impair healing in human wound model.

Venous leg ulcers (VLUs) represent one of the most prevalent types of chronic wounds characterised by perturbed microbiome and biofilm-forming bacteria. As one of the most abundant skin-commensal, Staphylococcus epidermidis is known as beneficial for the host, however, some strains can form biofilms and hinder wound healing. In this study, S. epidermidis distribution in VLUs and associated resistome were analysed in ulcer tissue from patients. Virulence of S. epidermidis isolates from VLUs were evaluated by whole genome sequencing, antimicrobial susceptibility testing, in vitro biofilm and binding assays, and assessment of biofilm-forming capability and pro-inflammatory potential using human ex vivo wound model. We demonstrated that S. epidermidis isolates from VLUs inhibit re-epithelialization through biofilm-dependent induction of IL-1β, IL-8, and IL-6 which was in accordance with impaired healing outcomes observed in patients. High extracellular matrix binding ability of VLU isolates was associated with antimicrobial resistance and expression levels of the embp and sdrG, responsible for bacterial binding to fibrinogen and fibrin, respectively. Finally, we showed that S. epidermidis from VLUs demonstrate pathogenic features with ability to impair healing which underscores the emergence of treatment-resistant virulent lineages in patients with chronic ulcers.

A Comprehensive Approach for Diabetic Foot Ulcer Management

Objectives: This study aims to evaluate the efficacy of a comprehensive management plan in the treatment of diabetic foot ulcers (DFUs). Evaluating the effects of wound debridement on the outcomes of diabetic foot ulcers, advanced dressings, blood sugar control, and offloading strategies are the main objectives. The study also intends to investigate the function of surgery in managing chronic ulcers and preventing recurrences. The goal is to offer advice for managing DFUs optimally and lowering related morbidity based on evidence. Method: The intervention program includes techniques like wound debridement, advanced dressings, unloading modalities, blood sugar level control, and, where necessary, surgical treatments. Growth factors, electrical stimulation, negative pressure wound therapy, bio-engineered skin, and hyperbaric oxygen therapy are among the many treatments that are included. Regression models are among the statistical analyses used to assess the efficacy of the overall management strategy. Results: Significant findings are presented in the results section, which shows how the holistic management strategy improves DFU outcomes. Improved wound healing rates, reduced infection incidents, and enhanced patient-reported outcomes are highlighted. The results underscore the significance of maintaining blood sugar levels, wound debridement, and incorporating various therapeutic modalities in DFU management. Conclusion: This study concludes by recommending a thorough and interdisciplinary approach to DFU management. Maintaining blood sugar levels, debridement of the wound, sophisticated dressings, unloading techniques, and surgical procedures are among the effective strategies that help reduce morbidity and prevent serious complications related to diabetic foot ulcers. Additional investigation is necessary to enhance and broaden these results for ongoing progress in the management of diabetic foot ulcers.

Quantification of muscle fiber malformations using edge detection to investigate chronic muscle pressure ulcers

BackgroundMicroscopy of regenerated tissue shows different morphologies between the healing of acute wounds and chronic wounds. This difference can be seen manually by biologists, but computational methods are needed to automate the characterization of morphology and regenerative quality in regenerated muscle tissue.ResultsFrom the detected edge segments, we computed several imaging biomarkers of interest, such as median tortuosity, number of edge segments normalized by area, median edge segment distance and interquartile range of orientation angles of edge segments of the microscope images of successful and unsuccessful muscle regeneration. We observed that muscle fibers in saline-treated pressure ulcers had a larger interquartile range of orientation angles of the edge segments (p = 0.05) and shorter edge segment distances (p = 0.003) compared to those of acute cardiotoxin injuries.ConclusionOur edge detection method was able to identify statistically significant differences in some of the imaging biomarkers between saline-treated pressure ulcers and cardiotoxin injuries, suggesting that chronic pressure ulcers have increased muscle fiber malformations compared to cardiotoxin injuries.

Clinical features of chronic tibial osteomyelitis: a single-center retrospective study of 282 cases in Xinjiang, China.

Chronic osteomyelitis is a highly prevalent and severe orthopaedic complication, representing a critical unresolved issue. The clinical symptoms of osteomyelitis are influenced by various factors, including geography, lifestyle, and pre-existing medical conditions.This study aims to provide theoretical basis for treatment and prevention of osteomyelitis by investigating and analyzing clinical features and pathogen distribution among 282 patients with chronic tibial osteomyelitis in xinjiang. A total of 282 patients with chronic tibial osteomyelitis from January 1, 2012 to January 1, 2022 in the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. All data were collected from electronic medical record (EMR) system including demographics, etiology, risk factors, osteomyelitis location and clinical classification. Farmers, students, unemployed and retirees accounted for a relatively large proportion of the 282 patients. There were 233 males and 49 females with a gender ratio of 4.75:1. The average age was 40.21 ± 15.68 years and was mainly concentrated in 41-50 years, specifically, the mean age of females was slightly older than that of males. Education level was mostly primary and secondary school education, and illiteracy. Risk factors of chronic tibial osteomyelitis included history of smoking and drinking, history of multiple repeated surgeries, and impaired immunity. Frequent clinical symptoms were in the order of pain, local swelling, pus discharge and skin ulceration. Among all inflammatory markers, proportion of positive results were 30.85%, 59.93% and 53.90% for white blood cell (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), respectively. Positive rate of pathogenic microorganism culture was low and the three most common bacteria were Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The most frequent site of infection was middle tibia. According to Cierny-Mader osteomyelitis classification, the most common types were type IIIA, IVA and IIA. Number of visits due to chronic osteomyelitis increased year by year, with young and middle-aged male farmers and low education level as the main groups. Smoking and drinking were two considerable risk factors that should be attached to a great importance. No significant increase was found in inflammatory markers and lower positive rate of pathogenic microorganism culture was observed. Multi-drug resistant bacteria were common and S. aureus remained the most frequent pathogen. Elevated ESR had certain diagnostic value for osteomyelitis. Type III and type IV osteomyelitis accounted for a large proportion which posed great challenges for clinical diagnosis and treatment.

Association of biofilm and microbial metrics with healing rate in older adults with chronic venous leg ulcers.

The presence of microbial biofilms in many human chronic wounds led to the hypothesis that biofilms delay healing of these wounds. We tested this hypothesis in a population of 117 older individuals with venous leg ulcers who were receiving standardised therapy, including frequent debridement. Debridement specimens were analysed for the amount of bacterial biomass by two independent methods: a microscopic approach that scored the relative size and number of bacterial aggregates, interpreted as a biofilm metric, and conventional enumeration by agar plating for viable bacteria. The plating protocol yielded three distinct values: the total viable bacterial count, bleach-tolerant bacteria, and the log reduction in viable bacteria upon bleach treatment. Wound healing rates over an 8-week observation period were calculated as the rate of decrease of the equivalent diameter of the wound. There was no statistically significant association between wound healing and the biofilm metric in any of the three analyses performed (p ≥0.15). In all three statistical tests, wound healing was associated with the log reduction caused by bleach treatment (p ≤0.004); wounds that harboured bacteria that were more bleach-susceptible healed more slowly. A refinement of the model of chronic wound infection pathogenesis is proposed in which dormant bacteria constitute a persistent nidus and outgrowth of metabolically active cells impairs healing. This model constitutes a new hypothesis as metabolic activity was not directly measured in this investigation.

Pathological and Fungal Isolation study of dog skin disease in Iraq Governorates

Dogs are susceptible to several types of infectious diseases can be worrisome for their owner because some of them are fatal if not treated soon enough. Fungal infection can be contracted through different parts of body furthermore many of them are zoonotic infection among human and dogs the signs of any disease typical depend on location of infection either local or system infection. Local infection usually involves skin surface that look like wound the objective of this study was to briefly about the most common pathogenic fungal infection in dogs by describing information about the causative agent, clinical signs and grossly appearance with histopathological change skin examination current study were done on 200 dogs collected in Iraq governorates (Baghdad, Erbil, Anbar, Sulaymaniyah) during a period 6 months (January – June) 2023. 200 examined dogs with different age, breed and sex ( k9, ornamental and stray dogs ) were observed fungal isolation and pathological examination with clinical signs by using diagnostic tools for skin biopsies (biopsy punch) from suspected infected skin dogs. Results showed pathogenic fungi after collected on fungal culture for detection pathogenic fungal (Dermatophyte Test Agar) D.T.M Agar Base. Fungal isolation constitutes the following pathogenic fungi (100 infected samples from 200 suspected samples). 60% Aspergillus niger, 30% Trichophyton Verrucosum, 10% Alternaria spp. Clinical signs and grossly lesion showed complete skin ulcer, allopecia, odema, abscessation while microscopic appearance revealed skin ulcer, hyperkeratosis, folliculitis, necrosis, apoptosis, pyogranuloma and granulation tissue with septate hyphae in skin dermis and epidermis which infected with Aspergillus niger.

MicroRNA Expression in Chronic Venous Leg Ulcers and Implications for Wound Healing: A Scoping Review.

Purpose: Chronic venous leg ulcers (CVLUs) comprise the majority of lower-extremity wounds, yet their pathophysiology is not fully understood. While research has shown that microRNAs are an important component of wound inflammation, few have explored the role of microRNAs (miRNAs) in the healing of CVLUs. This scoping review examines miRNAs in CVLUs and the association with wound healing. Methods: In December 2023, we searched MEDLINE/PubMed, Embase, Scopus, and CINAHL for studies published in 2013-2023 examining miRNAs in CVLU healing. Results: Six studies met inclusion criteria. MicroRNAs were extracted from various specimens including serum, skin biopsy samples, and adipose tissue-derived mesenchymal cells from individuals with CVLUs. Overexpression of miR-221, miR-222, miR-92a, and miR-301a-3p hindered angiogenesis, while overexpression of miR-296, miR-126, miR-378, and miR-210 facilitated angiogenesis. Overexpression of miR-34a/c, miR-301a-3p, miR-450-5p, miR-424-5p, miR-516-5p, and miR-7704 increased local inflammatory responses and inhibited keratinocytes proliferation, impairing healing, while overexpression of miR-19a/b and miR-20 downregulated keratinocytes' inflammatory response, promoting healing. Downregulation of miR-205, miR-96-5p, and miR-218-5p enhanced cellular proliferation and promoted wound healing. Downregulation of miR-17-92 was linked with impaired healing. Discussion: MicroRNAs play a role in regulating angiogenesis, inflammatory responses, and cell migration in chronic-wound healing. However, studies of miRNAs in CVLUs are limited and lack a standardized approach to measurement and quantification. Further research is warranted to elucidate the mechanisms underlying microRNA involvement in CVLU healing to better understand the pathophysiology and for the future development of targeted therapies.

Comprehensive evaluation and management of chronic gastritis in a dog: A case report

Gastric ulcer is a significant clinical issue in dogs, with higher prevalence in mature animals and often occurs secondary to systemic diseases such as hepatic or renal disorders, Addison’s disease or shock. This case report highlights a four-and-a-half-year-old intact male Rottweiler presented with persistent vomiting, anorexia, abdominal pain and anemia. Diagnostic imaging, including radiography, ultrasonography and endoscopy, revealed gastric ulceration and the presence of radiopaque lead pellets in the pyloric region of the stomach. Histopathological examination confirmed extensive gastric mucosal damage.Treatment included the elimination of lead, fluid therapy and administration of proton pump inhibitors, antibiotics and mucosal protectants. Incorporating psyllium husk into the diet helped to enhance lead excretion. Follow-up imaging after two weeks showed absence of lead pellets and normal gastric mucosa. This case underscores the importance of comprehensive diagnostic and therapeutic approaches for chronic gastric ulcers in dogs, emphasising the role of multimodal imaging and targeted treatment strategies. Keywords: Dog, gastric ulcers, diagnostics, therapeutics

Evaluation of the effect of ozone olive oil and laser photobiomodulation on the tissue repair of traumatic ulcer on the rat tongue

ABSTRACT The objective of this study was to evaluate the effect of ozonized olive oil with or without laser photobiomodulation (LPBM) on the healing process of traumatic ulcers in rat tongues. Sixty male Wistar rats underwent tongue ulceration using a six-mm diameter punch. Animals were divided into four experimental groups: control-G1, LPBM-G2, Ozonized olive oil-G3, and LPBM + Ozonized olive oil-G4. Euthanasia was performed on days three, seven, and 14. Clinical analysis of the wound size and histomorphological evaluation using hematoxylin and eosin and Sirius red staining were conducted to identify edema, inflammatory infiltrates, fibroblastic cellularity, reepithelialization, and collagen characterization. Descriptive and exploratory analyses were performed using R and inferential statistics were calculated using Fisher’s exact tests, with a significance level of 5%. G2 and G3 positively modulated the repair phases clinically (p < 0.05) and histologically, showing reepithelialization, fibroblastic population, and thick collagen fiber deposition from the 3rd day of the experiment. G4 exhibited a significant difference from G1 in the clinical parameters (p < 0.05), but did not demonstrate superiority in histomorphological terms of tissue repair. Isolated use of LPBM and ozonized olive oil improved tissue repair in rat tongues.

Mechanism of cold atmospheric plasma in treatment of chronic skin ulcer

To review the mechanism of cold atmospheric plasma (CAP) in the treatment of chronic skin ulcer, providing a new idea for ulcer therapy. The literature about CAP in the treatment of chronic skin ulcers in recent years was extensively screened and reviewed. The treatment principle, active ingredients, and mechanism were summarized. CAP is partial ionized gas discharged by plasma generator in high frequency under high voltage. It contains electrons, positive and negative ions, reactive oxygen species, reactive nitrogen species, and ultraviolet rays. In vitro and animal experiments show that the active ingredients contained in CAP can inactive microorganisms, against biofilm, regulate immune-mediated inflammatory, promoting blood flow, stimulate tissue regeneration and epithelial formation in the course of wounds healing. CAP play a role in different stages of chronic skin ulcer healing, with good effectiveness and safety, and broad clinical application prospects. But more studies are needed to explore the indications and dosages of CAP therapy.

Application of Drug Delivery System Based on Nanozyme Cascade Technology in Chronic Wound.

Chronic wounds are characterized by long-term inflammation, including diabetic ulcers, traumatic ulcers, etc., which provide an optimal environment for bacterial proliferation. At present, antibiotics are the main clinical treatment method for chronic wound infections. However, the overuse of antibiotics may accelerate the emergence of drug-resistant bacteria, which poses a significant threat to human health. Therefore, there is an urgent need to develop new therapeutic strategies for bacterial infections. Nanozyme-based antimicrobial therapy (NABT) is an emerging antimicrobial strategy with broad-spectrum activity and low drug resistance compared to traditional antibiotics. NABT has shown great potential as an emerging antimicrobial strategy by catalyzing the generation of reactive oxygen species (ROS) with its enzyme-like catalytic properties, producing a powerful bactericidal effect without developing drug resistance. Nanozyme-based cascade antimicrobial technology offers a new approach to infection control, effectively improving antimicrobial efficacy by activating cascades against bacterial cell membranes and intracellular DNA while minimizing potential side effects. However, it is worth noting that this technology is still in the early stages of research. This article comprehensively reviews wound classification, current methods for the treatment of wound infection, different types of nanozymes, the application of nanozyme cascade reaction technology in antimicrobial therapy, and future challenges and prospects.

Device-measured stationary behaviour and cardiovascular and orthostatic circulatory disease incidence.

Previous studies have indicated that standing may be beneficially associated with surrogate metabolic markers, whereas more time spent sitting has an adverse association. Studies assessing the dose-response associations of standing, sitting and composite stationary behaviour time with cardiovascular disease (CVD) and orthostatic circulatory disease are scarce and show an unclear picture. To examine associations of daily sitting, standing and stationary time with CVD and orthostatic circulatory disease incidence. We used accelerometer data from 83 013 adults (mean age ± standard deviation = 61.3 ± 7.8; female = 55.6%) from the UK Biobank to assess daily time spent sitting and standing. Major CVD was defined as coronary heart disease, heart failure and stroke. Orthostatic circulatory disease was defined as orthostatic hypotension, varicose vein, chronic venous insufficiency and venous ulcers. To estimate the dose-response hazard ratios (HR) we used Cox proportional hazards regression models and restricted cubic splines. The Fine-Gray subdistribution method was used to account for competing risks. During 6.9 (±0.9) years of follow-up, 6829 CVD and 2042 orthostatic circulatory disease events occurred. When stationary time exceeded 12 h/day, orthostatic circulatory disease risk was higher by an average HR (95% confidence interval) of 0.22 (0.16, 0.29) per hour. Every additional hour above 10 h/day of sitting was associated with a 0.26 (0.18, 0.36) higher risk. Standing more than 2 h/day was associated with an 0.11 (0.05, 0.18) higher risk for every additional 30 min/day. For major CVD, when stationary time exceeded 12 h/day, risk was higher by an average of 0.13 (0.10, 0.16) per hour. Sitting time was associated with a 0.15 (0.11, 0.19) higher risk per extra hour. Time spent standing was not associated with major CVD risk. Time spent standing was not associated with CVD risk but was associated with higher orthostatic circulatory disease risk. Time spent sitting above 10 h/day was associated with both higher orthostatic circulatory disease and major CVD risk. The deleterious associations of overall stationary time were primarily driven by sitting. Collectively, our findings indicate increasing standing time as a prescription may not lower major CVD risk and may lead to higher orthostatic circulatory disease risk.

Deep Fungal Infections of Skin and Role of Histopathology in Diagnosis

Abstract Introduction: Deep mycoses acquired by penetrating trauma to the skin can have varied and sometimes atypical morphological presentations resulting in diagnostic dilemmas and delay in treatment onset. Histopathology can be a useful tool in not only diagnosing but also differentiating various deep mycoses. Aims and Objectives: To observe various morphological presentations and histopathological features of deep fungal infections. Materials and Methods: A retrospective multi-centric study was conducted from 2010 to 2020 at 16 centres. The cases with diagnoses of various deep mycoses were included in the study. The patients presenting with cutaneous manifestations were included in the study. Their demographic details, history, presenting signs and symptoms, morphological presentations, histopathological features and treatment details were collected from the case sheets. Results: A total of 124 cases were found from the case records. The most common type was chromoblastomycosis (42) followed by mycetoma (28) and rhinosporidiosis (17). The mean age was 43.76 ± 5.44 years. The average duration of symptoms before presentation was between 2 months to 10 years (average 2.5 ± 1.33 years). Male to female ratio was 1:0.7. Prior history of trauma was recorded in 36% of cases. Chromoblastomycosis cases presented with verrucous to atrophic plaques with black dots on the surface and histopathology findings included pesudoepitheliomatous hyperplasia, epithelioid cell granulomas, copper penny bodies within granulomas and abscesses. Rhinosporidiosis cases had polypoid grape-like lesions in the nose and eyes most commonly with histopathology findings of abundant thick-walled sporangia in dermis packed with thousands of spores. Eumycetoma patients had pigmented, indurated swelling with multiple sinuses discharging black granules and histopathology showed dermal abscesses and foreign body granulomatous reaction with PAS-positive hyphae. Histoplasmosis patients presented with few to multiple nodulo-pustular lesions on skin and palatal ulcers while small basophilic bodies packed in the cytoplasm of histiocytes were noted in histopathology. Phaeohyphomycosis cases presented as deep-seated cystic lesions and biopsy revealed deepithelialized cysts in the dermis or hypodermis with lumen showing necro inflammatory debris and fungal hyphae. Sporotrichosis cases had erythematous, tender nodules and papules either as single lesions or as multiple lesions arranged in a linear fashion and histopathology showed pseudoepitheliomatous hyperplasia of epidermis, loose to well-defined epithelioid cell granulomas and microabscesses. Spores were found in two cases. Cryptococcosis patient had multiple umbilicated lesions resembling giant molluscum contagiosum loose epithelioid cell granulomas and medium-sized spores lying in both intra and extracellularly on histopathology. Penicilliosis patients had nodulo-pustular lesions and histopathology showed an admixture of histiocytes, epithelioid cells, plasma cells, lymphocytes and polymorphs in the dermis with the presence of yeast-like spores in the cytoplasm of histiocytes and epithelioid cells. Entomophthoromycosis cases presented with asymptomatic subcutaneous firm swelling with loss of skin pinchability. Conclusion: Though clinical findings of deep fungal infections are characteristic similar morphology and atypical presentations can be sometimes confusing. Histopathology is useful for confirming the diagnosis.