ABSTRACT
Exercise is believed to be beneficial for skeletal muscle functions across all ages. Regimented exercise is often prescribed as an effective treatment/prophylaxis for age-related loss of muscle mass and function, known as sarcopenia, and plays an important role in the maintenance of mobility and functional independence in the elderly. However, response to exercise declines with aging, resulting in limited gain of muscle strength and endurance. These changes likely reflect age-dependent alterations in transcriptional response underlying the muscular adaptation to exercise. The exact changes in gene expression accompanying exercise, however, are largely unknown, and elucidating them is of a great clinical interest for understanding and optimizing the exercise-based therapies for sarcopenia. In order to characterize the exercise-induced transcriptomic changes in aged muscle, a paired-end RNA sequencing was performed on rRNA-depleted total RNA extracted from the gastrocnemius muscles of 24 months-old mice after 8 weeks of regimented exercise (exercise group) or no formal exercise program (sedentary group). Differential gene expression analysis of aged skeletal muscle revealed upregulations in the group of genes involved in neurotransmission and neuroexcitation, as well as equally notable absence of anabolic gene upregulations in the exercise group. In particular, genes encoding the transporters and receptor components of glutaminergic transmission were significantly upregulated in exercised muscles, as exemplified by Gria 1, Gria 2 and Grin2c encoding glutamate receptor 1, 2 and 2C respectively, Grin1 and Grin2b encoding N-methyl-d-aspartate receptors (NMDARs), Nptx1 responsible for glutaminergic receptor clustering, and Slc1a2 and Slc17a7 regulating synaptic uptake of glutamate. These changes were accompanied by an increase in the post-synaptic density of NMDARs and acetylcholine receptors (AChRs), as well as their innervation at neuromuscular junctions (NMJs). These results suggest that neural responses predominate the adaptive response of aged skeletal muscle to exercise, and indicate a possibility that glutaminergic transmission at NMJs may be present and responsible for synaptic protection and neural remodeling accompanying the exercise-induced functional enhancement in aged skeletal muscle. In addition, the absence of upregulations in the anabolic pathways highlights them as the area of potential pharmacological targeting for optimizing exercise-led sarcopenia therapy.
Subject(s)
Muscle, Skeletal , Sarcopenia , Aging/genetics , Animals , Gene Expression , Mice , Muscle, Skeletal/metabolism , Neuromuscular Junction/metabolism , Sarcopenia/genetics , Sarcopenia/pathologyABSTRACT
OBJECTIVE: To determine if the various three-dimensional structures of bioscaffolds affect wound healing by investigating the efficacy of different porcine-derived urinary bladder matrix (UBM) structures in treating murine diabetic wound healing. METHODS: The authors studied three different UBM structures: particulate (pUBM), one-layer freeze-dried sheet (fdUBM), and three-layer laminated sheet (lmUBM). Scanning electron microscopy images of the structures were used to calculate a wound-exposed surface-area-to-volume ratio. A 1.0 × 1.0-cm full-thickness dorsal wound was excised on 90 db/db mice. Mice were either untreated (blank, n = 15), treated with one UBM structure (pUBM, n = 15; fdUBM, n = 15; lmUBM, n = 15), or treated with a combination of either the one- or three-layer sheet over the particulate matrix (fdUBM + pUBM, n = 15; lmUBM + pUBM, n = 15). The authors obtained macroscopic images of the wounds and harvested tissues for analyses at multiple time points. RESULTS: The surface area available to interact with the wound was highest in the pUBM group and lowest in the lmUBM group. Greater wound bed thickness was noted in the fdUBM, fdUBM + pUBM, and lmUBM groups compared with the blank group. Cellular proliferation was significantly higher in the fdUBM and fdUBM + pUBM groups than in the blank group. The lmUBM + pUBM group had the highest collagen deposition. The pUBM group induced significantly higher leukocyte infiltration compared with the lmUBM, lmUBM + pUBM, and blank groups. Microvessel density was highest in the fdUBM + pUBM group. Significant differences in the wound closure rate were noted between the blank group and the fdUBM and fdUBM + pUBM groups. CONCLUSIONS: Assessment of the three UBM bioscaffold structures highlighted differences in the wound-exposed surface area. Variations in wound healing effects, including collagen deposition, cellular proliferation, and angiogenesis, were identified, with combinations of the structures displaying synergistic effects. This study serves as a platform for future scaffold design and offers promising evidence of the benefits of combining various structures of scaffolds.
Subject(s)
Diabetes Mellitus , Urinary Bladder , Animals , Biology , Collagen , Humans , Mice , Swine , Wound HealingABSTRACT
BACKGROUND & OBJECTIVES: Leishmania parasites are sensitive to very low temperature. Cryotherapy is considered as an alternative to the existing pentavalent antimonials, for local treatment of cutaneous leishmaniasis (CL). Normally, liquid nitrogen (N2) at a temperature of -196 °C, is used in cryotherapy of CL, but it's efficacy is not consistent. Recently, few studies have also reported the use of carbon dioxide (CO2) slush at -78.5 °C in CL cryotherapy. This study was aimed to evaluate the effectiveness of N2 vs CO2 cryotherapy for CL treatment in mice. Methods: In total, 21 BALB/c mice were infected with Leishmania major strain [MRHO/IR/74/ER]. Samples were divided into three groups based on the intervention provided-Solid CO2 cryotherapy, liquid N2 cryotherapy and control group; with seven mice randomly assigned to each group. Control group received no intervention, and in the other two groups cryotherapy was used every two weeks for maximum of three months. Follow up examinations were scheduled at the time of cryotherapy, during which the size of each lesion was measured. For three mice in each study group, the spleen parasite DNA load was quantified using real-time PCR. RESULTS: After treatment, the liquid N2 cryotherapy showed significant reduction in size of the lesions (p = 0.029) as compared to the solid CO2 cryotherapy and control group. Also, Leishmania DNA load in spleen was significantly lower in the mice receiving liquid N2 cryotherapy (p <0.001). INTERPRETATION & CONCLUSION: Liquid N2 cryotherapy is superior to CO2 cryotherapy, and it can be an effective method for controlling L. major infection. Further investigations are essential to find optimal number of treatment sessions and time intervals.
Subject(s)
Carbon Dioxide/therapeutic use , Cryotherapy/methods , Leishmania major , Leishmaniasis, Cutaneous/therapy , Nitrogen/therapeutic use , Administration, Cutaneous , Animals , Carbon Dioxide/administration & dosage , Female , Leishmania major/genetics , Leishmania major/isolation & purification , Leishmania major/physiology , Leishmaniasis, Cutaneous/parasitology , Mice , Mice, Inbred BALB C , Nitrogen/administration & dosage , Parasite Load , Random Allocation , Spleen/parasitologyABSTRACT
A simple efficacious topical treatment for cutaneous leishmaniasis (CL) is still an unresolved challenge. This study aimed to evaluate the efficacy of the topical use of thioxolone plus benzoxonium chloride (Thio-Ben) tincture in combination with cryotherapy in comparison with intralesional meglumine antimoniate (Glucantime) along with cryotherapy in treating anthroponotic CL (ACL). The study was conducted in Leishmaniasis Center in Dadbin Health Care Clinic, Kerman, Iran. Sixty-four CL lesions were randomly assigned to receive Thio-Ben plus cryotherapy (TC) (n = 32) or Glucantime plus cryotherapy (GC) (n = 32). Thio-Ben was used topically every other day and Glucantime was used intralesionally once a week for a maximum of 3 months. In both study groups, cryotherapy was administered using liquid nitrogen once every 2 weeks. Of 64 recruited lesions, 47 lesions completed the study protocol. Twenty lesions (91%) in TC group and 23 lesions (92%) in GC group showed complete cure. TC group showed faster clinical response. Pain, hypersensitivity reaction, dizziness, and nausea were only seen in GC group. This study showed that the topical use of Thio-Ben combined with cryotherapy has a good efficacy in treating ACL with the benefit that Thio-Ben has more patient compliance and less side effects than intralesional Glucantime.
Subject(s)
Anti-Infective Agents, Local/administration & dosage , Benzalkonium Compounds/administration & dosage , Cryotherapy , Lactones/administration & dosage , Leishmaniasis, Cutaneous/therapy , Adolescent , Adult , Antiprotozoal Agents/administration & dosage , Child , Child, Preschool , Combined Modality Therapy , Drug Administration Schedule , Drug Combinations , Female , Humans , Iran , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/parasitology , Male , Meglumine/administration & dosage , Meglumine Antimoniate , Molecular Sequence Data , Organometallic Compounds/administration & dosage , Patient Compliance , Recurrence , Remission Induction , Single-Blind Method , Time Factors , Treatment Outcome , Young AdultABSTRACT
Background: Response to the current available treatments of melasma, dermal type, in particular, is usually gradual and can result in possible side effects. Aim and Objectives: In this study, we aim to evaluate the efficacy of the combination of plasma rich in growth factors (PRGF) and topical 4% hydroquinone (HQ) in comparison with monotherapy using topical 4% HQ alone in the treatment of dermal type of melasma. Materials and Methods: This is a single-blinded, randomized, split-face clinical trial on twenty female patients with dermal type of melasma. Patients were asked to apply topical 4% HQ on both sides of their face at night for 6 months. In each participant, one side of the face was randomly chosen to receive monthly intradermal injections of PRGF for 3 sessions. Efficacy of the treatment was assessed using hemi melasma area and severity index (MASI) score, physician's global assessment (PGA), and patients' global assessment (PtGA). Results: Both groups revealed significant improvement in hemi-MASI score during the treatment course. Mean percentage of improvement at the end of study was 40.38 ± 6.04% and 33.42 ± 3.23% in the combination therapy and monotherapy groups, respectively (P = 0.31). PGA demonstrated excellent-to-marked improvement in melasma in 25% and 5% of patients in the combination therapy and monotherapy groups, respectively (P = 0.31). PtGA showed high levels of satisfaction in 15% of patients in the combination therapy group (vs. 0% in the monotherapy group) (P = 0.05). Conclusion: Differences between the two treatment groups in terms of hemi-MASI and PGA scores were not statistically significant; however, patients demonstrated higher satisfaction with combination of PRGF and topical 4% HQ compared with topical HQ alone. Thereby, combination of PRGF and topical 4% HQ can be suggested as a safe alternative therapeutic approach and may hold promise in the development of future therapeutic options for dermal type of melasma.
ABSTRACT
PURPOSE: Obesity exerts negative effects on pulmonary function through proven mechanical and biochemical pathways. Multiple studies have suggested that bariatric surgery can improve lung function. However, the timing of these effects on lung function and its association with patient reported outcomes is not known. MATERIALS AND METHODS: A prospective cohort study of patients undergoing laparoscopic sleeve gastrectomy (LSG) at a tertiary care hospital was undertaken. Spirometry tests, laboratory tests, and self-reported questionnaires on asthma symptoms and asthma control (ACQ and ACT) were administered. All data were recorded pre-operatively (T0) and every 3 months post-operatively for 1 year (T3, T6, T9, T12) and were compared using a mixed-models approach for repeated measures. RESULTS: For the 23 participants, mean age was 44.2 ± 12.3 years, mean BMI was 45.2 ± 7.2 kg/m2, 18(78%) were female, 9(39%) self-reported as non-white and 6(26%) reported to have asthma. Following LSG, % total body weight loss was significant at all follow-up points (P < 0.0001). Rapid improvement in forced expiratory volume (FEV)% predicted and forced vital capacity (FVC)% predicted was seen at T3. Although the overall ACQ and ACT score remained within normal range throughout the study, shortness of breath declined significantly at 3 months post-op (P < 0.05) and wheezing resolved for all patients by twelve months. Patients also reported reduced frequency of sleep interruption and inability to exercise by the end of the study (P < 0.05). CONCLUSION: Improvements in objective lung function assessments and patient-reported respiratory outcomes begin as early as 3 months and continue until 12 months after sleeve gastrectomy.
Subject(s)
Gastrectomy , Obesity, Morbid , Patient Reported Outcome Measures , Weight Loss , Humans , Female , Male , Adult , Prospective Studies , Obesity, Morbid/surgery , Obesity, Morbid/physiopathology , Obesity, Morbid/complications , Gastrectomy/methods , Weight Loss/physiology , Middle Aged , Forced Expiratory Volume , Lung/physiopathology , Vital Capacity , Asthma/physiopathology , Treatment Outcome , Laparoscopy , Respiratory Function TestsABSTRACT
INTRODUCTION: Tissue engineering is a revolutionized biotechnology that utilizes biomaterials in regenerative medicine. Nowadays, there is a trend in employing autologous-based materials in aesthetic medicine. In this review, we discuss safety and efficacy of autologous-based fillers in the fields of aesthetic dermatology, and describe the details of preparation and injection methods based on current literature. EVIDENCE ACQUSITION: PubMed, Scopus, Web of science, Embase and Google scholar were searched for studies which evaluated efficacy of autologous-based filler in the field of aesthetic dermatology from January 2000 until August 2022. Nineteen articles including five randomized clinical trials, ten prospective and four retrospective studies were selected for this review. EVIDENCE SYNTHESIS: Most of the studies evaluated use of biofillers in rejuvenation (twelve articles) and the remaining were in atrophic scars (six articles) and striae distensae (one article). Adjuvant treatments included liquid platelet rich growth factor (PRGF), autologous cultured fibroblast, adipose tissue micrograft, microneedling, fractional carbon dioxide laser and subcision. Application of biofillers is a safe alternative therapeutic option for soft tissue augmentation. CONCLUSIONS: Application of biofillers is especially recommended in patients who seek low-cost rejuvenation methods and those with a past history of granulomatous reactions to the other fillers. It provides the advantage of immediate filling effects with long-lasting efficacy.
Subject(s)
Cosmetic Techniques , Dermatology , Humans , Prospective Studies , Retrospective Studies , EstheticsABSTRACT
Objective: The development of animal models, which adequately replicate the pathophysiology of chronic wounds, has been challenging. In this study, we utilized an oxidative stress (OS) murine model, which was previously developed by our group, to study the effect of a human amniotic membrane (AM) on chronic wound healing. Approach: Forty-five diabetic (genetically obese leptin receptor-deficient mice [db/db]) mice were separated into three groups. Thirty mice received an OS regimen and a 1 - × 1 cm2 full-thickness excisional dorsal wound. The wounds were either covered with AM and occlusive dressing (db/dbOS-AM) or occlusive dressing only (db/dbOS). Fifteen mice did not receive the OS regimen, and were covered with AM and occlusive dressing (db/db-AM). The wounds were photographed, and tissue was harvested at various time points. Results: Vascular density was higher in the AM-treated groups (db/dbOS-AM: 34 ± 12; db/db-AM: 37 ± 14; vs. db/dbOS: 19 ± 9 cluster of differentiation 31 [CD31+]/high power field [HPF] photograph; p = 0.04 and p = 0.003). Vessel maturity was lowest in the db/dbOS group (21% ± 4%; vs. db/dbOS-AM: 38% ± 10%, p = 0.004; db/db-AM: 40% ± 11%, p = 0.0005). Leukocyte infiltration was higher in the AM groups (db/dbOS-AM: 15 ± 4; db/db-AM: 16 ± 4 vs. db/dbOS: 8 ± 3 lymphocyte common antigen [CD45+]/HPF; p = 0.005 and p = 0.06). AM upregulated various proangiogenic factors, including vascular endothelial growth factor (VEGF), and downregulated genes involved in chronicity, such as osteopontin, as visualized through proteome analysis and western blotting. Cell death was lower in the AM groups (db/dbOS-AM: 28 ± 10, db/db-AM: 7 ± 5 vs. db/dbOS: 17% ± 9% Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling [TUNEL+]; p = 0.03 and p < 0.0001). Innovation: This study offers new insight on the mechanisms of action of human AM in chronic wound healing. Conclusion: AM treatment promoted healing in mice with complex chronic wounds. The AM stimulated angiogenesis through upregulation of proangiogenic factors, improving the wound milieu by increasing leukocyte and growth factor delivery and decreasing cell death.
Subject(s)
Diabetes Mellitus , Vascular Endothelial Growth Factor A , Mice , Humans , Animals , Amnion , Wound HealingABSTRACT
Aim: Volumetric muscle loss (VML) is a composite loss of skeletal muscle, which heals with fibrosis, minimal muscle regeneration, and incomplete functional recovery. This study investigated whether collagen-glycosaminoglycan scaffolds (CGS) improve functional recovery following VML. Methods: 15 Sprague-Dawley rats underwent either sham injury or bilateral tibialis anterior (TA) VML injury, with or without CGS implantation. Results: In rats with VML injuries treated with CGS, the TA exhibited greater in vivo tetanic forces and in situ twitch and tetanic dorsiflexion forces compared with those in the non-CGS group at 4- and 6-weeks following injury, respectively. Histologically, the VML with CGS group demonstrated reduced fibrosis and increased muscle regeneration. Conclusion: Taken together, CGS implantation has potential augment muscle recovery following VML.
Volumetric muscle loss (VML) is a large injury to skeletal muscle. VML heals with scarring, little muscle regeneration, and incomplete strength recovery. The current treatment for VML involves transferring muscle from one part of the body to the injury site. However, this is limited by weakness of the donor site and incomplete recovery of muscle function. Therefore, other treatments have been developed to aid in muscle healing. One such treatment involves using three dimensional templates, known as scaffolds, to aid in muscle regeneration. Our goal is to determine whether a collagenglycosaminoglycan scaffold (CGS), which is already used for other medical purposes, can improve healing of VML injuries in rats. CGS placement in rat muscle injuries resulted in decreased scarring, increased muscle regeneration, and increased strength recovery compared with the non-CGS group.
Subject(s)
Muscular Diseases , Regeneration , Rats , Animals , Glycosaminoglycans , Rats, Sprague-Dawley , Muscle, Skeletal , Muscular Diseases/pathology , Muscular Diseases/therapy , Collagen , FibrosisABSTRACT
BACKGROUND: Decreased lymphangiogenesis contributes to impaired diabetic wound healing. Although negative-pressure wound therapy (NPWT) has been shown to be effective in the treatment of recalcitrant wounds, its impact on lymphangiogenesis remains to be elucidated. In this study, the authors investigate the mechanisms of lymphangiogenesis following NPWT treatment of diabetic murine wound healing. METHODS: Full-thickness dorsal skin wounds (1 × 1 cm 2 ) were excised on 30 db/db mice. The mice were either treated with occlusive covering (control group, n = 15), or received a 7-day treatment of continuous NPWT at -125 mmHg (NPWT group, n = 15). The wounds were photographed on days 0, 7, 10, 14, 21, and 28. Wound tissue was harvested on days 10, 14, 21, and 28 for quantitative analysis. Functional analysis of lymphatic drainage was performed on days 14 and 28 with Evans blue dye tracing. RESULTS: Lymphatic density and diameter, as visualized through podoplanin probing, was significantly higher in the NPWT group compared to the control group ( P < 0.001). NPWT up-regulated the expression of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) at the protein level ( P = 0.04), and significant differences were noted in lymphatic density as assessed by LYVE-1 staining ( P = 0.001). Leukocyte infiltration was significantly higher in the NPWT group ( P = 0.01). A higher speed of wound closure ( P < 0.0001) and greater wound bed thickness ( P < 0.0001) were noted in the NPWT group compared to the control group. CONCLUSIONS: NPWT increased the lymphatic vessel density and diameter with LYVE-1 up-regulation. NPWT therefore plays a positive role in lymphangiogenesis in diabetic wound healing. CLINICAL RELEVANCE STATEMENT: The authors' study investigates the association of NPWT and lymphatics and underlines the importance of a more in-depth investigation of the role of lymphatic vessels in wound healing.
Subject(s)
Diabetes Mellitus , Negative-Pressure Wound Therapy , Soft Tissue Injuries , Mice , Animals , Lymphangiogenesis , Wound Healing , Soft Tissue Injuries/therapyABSTRACT
Volumetric muscle loss (VML), which refers to a composite skeletal muscle defect, most commonly heals by scarring and minimal muscle regeneration but substantial fibrosis. Current surgical interventions and physical therapy techniques are limited in restoring muscle function following VML. Novel tissue engineering strategies may offer an option to promote functional muscle recovery. The present study evaluates a colloidal scaffold with hierarchical porosity and controlled mechanical properties for the treatment of VML. In addition, as VML results in an acute decrease in insulin-like growth factor 1 (IGF-1), a myogenic factor, the scaffold was designed to slowly release IGF-1 following implantation. The foam-like scaffold is directly crosslinked onto remnant muscle without the need for suturing. In situ 3D printing of IGF-1-releasing porous muscle scaffold onto VML injuries resulted in robust tissue ingrowth, improved muscle repair, and increased muscle strength in a murine VML model. Histological analysis confirmed regeneration of new muscle in the engineered scaffolds. In addition, the scaffolds significantly reduced fibrosis and increased the expression of neuromuscular junctions in the newly regenerated tissue. Exercise training, when combined with the engineered scaffolds, augmented the treatment outcome in a synergistic fashion. These data suggest highly porous scaffolds and exercise therapy, in combination, may be a treatment option following VML.
Subject(s)
Insulin-Like Growth Factor I , Muscular Diseases , Mice , Animals , Porosity , Regeneration , Muscle, Skeletal/physiology , Muscular Diseases/pathology , Tissue Engineering , Fibrosis , Physical Therapy Modalities , Tissue ScaffoldsABSTRACT
OBJECTIVES: Protecting frontline health care workers with personal protective equipment (PPE) is critical during the coronavirus disease (COVID-19) pandemic. Through an online survey, we demonstrated variable adherence to the Centers for Disease Control and Prevention (CDC) PPE guidelines among health care personnel (HCP). METHODS: CDC guidelines for optimal and acceptable PPE usage in common situations faced by frontline health care workers were referenced to create a short online survey. The survey was distributed to national, statewide, and local professional organizations across the United States and to HCP, using a snowball sampling technique. Responses were collected between June 15 and July 17, 2020. RESULTS: Responses totaling 2245 were received from doctors, nurses, midwives, paramedics, and medical technicians in 44 states. Eight states with n > 20 (Arizona, California, Colorado, Louisiana, Oregon, South Carolina, Texas, and Washington) and a total of 436 responses are included in the quantitative analysis. Adherence to CDC guidelines was observed to be highest in the scenario of patient contact when COVID-19 was not suspected (86.47%) and lowest when carrying out aerosol generating procedures (AGPs) (42.47%). CONCLUSIONS: Further research is urgently needed to identify the reasons underlying variability between professions and regions to pinpoint strategies for maximizing adherence and improving the safety of HCPs.
Subject(s)
COVID-19 , Pandemics , United States/epidemiology , Humans , Pandemics/prevention & control , Personal Protective Equipment , COVID-19/epidemiology , COVID-19/prevention & control , Health Personnel , Delivery of Health CareABSTRACT
OBJECTIVES: The coronavirus disease 2019 (COVID-19) is a resource-intensive global pandemic. It is important for healthcare systems to identify high-risk COVID-19-positive patients who need timely health care. This study was conducted to predict the hospitalization of older adults who have tested positive for COVID-19. METHODS: We screened all patients with COVID test records from 11 Mass General Brigham hospitals to identify the study population. A total of 1495 patients with age 65 and above from the outpatient setting were included in the final cohort, among which 459 patients were hospitalized. We conducted a clinician-guided, 3-stage feature selection, and phenotyping process using iterative combinations of literature review, clinician expert opinion, and electronic healthcare record data exploration. A list of 44 features, including temporal features, was generated from this process and used for model training. Four machine learning prediction models were developed, including regularized logistic regression, support vector machine, random forest, and neural network. RESULTS: All 4 models achieved area under the receiver operating characteristic curve (AUC) greater than 0.80. Random forest achieved the best predictive performance (AUC = 0.83). Albumin, an index for nutritional status, was found to have the strongest association with hospitalization among COVID positive older adults. CONCLUSIONS: In this study, we developed 4 machine learning models for predicting general hospitalization among COVID positive older adults. We identified important clinical factors associated with hospitalization and observed temporal patterns in our study cohort. Our modeling pipeline and algorithm could potentially be used to facilitate more accurate and efficient decision support for triaging COVID positive patients.
Subject(s)
COVID-19 , Aged , Electronic Health Records , Hospitalization , Humans , Machine Learning , PandemicsABSTRACT
External volume expansion (EVE) has been shown to improve fat graft survival. In this study, we investigated the xenogenic implantation of human allograft adipose matrix (AAM) in non-immunocompromised mice in combination with pre- and post-conditioning with EVE to assess long-term adipose tissue survival. Sixty-eight recipient sites in thirty-four eight-week-old wild type (C57BL/6J) mice were separated into four groups. Thirty-four sites received no conditioning and either a subcutaneous injection of 300 µl saline (n= 17; PBS group) or AAM (n= 17; AAM group). Thirty-four sites received pre-conditioning with EVE (Day -7-3 pre-grafting) and 300 µl of AAM. Seventeen of these sites received immediate post-conditioning (Day 1-5 post-grafting) and 17 delayed post-conditioning (Day 28-32 post-grafting). Tissue was harvested at week 12 for analysis. At 12 weeks, immediate and delayed post-conditioning enabled higher volume retention (p= 0.02 andp< 0.0001, respectively). Adipose Stem Cells were greater in the AAM+Del-EVE group compared to the AAM (p= 0.01). Microvessel density was lower in the AAM group compared to the AAM+Imm-EVE (p= 0.04) and AAM+Del-EVE group (p= 0.02). Macrophage infiltration was lower in the AAM+Imm-EVE (p= 0.002) and AAM+Del-EVE (p= 0.003) groups compared to the AAM group. PCR analysis and Western blotting identified a significantly higher expression of PPAR-γ, LPL and VEGF with delayed-conditioning. Pre- and post-conditioning, particularly delayed-post-conditioning, of the recipient site optimized the microenvironment allowing significant adipogenesis and survival of neo-adipose tissue through robust angiogenesis. This study supports that xenogenic transplantation of adipose matrix allows adipose tissue formation and survival with EVE as an adjuvant.
Subject(s)
Peroxisome Proliferator-Activated Receptors , Vascular Endothelial Growth Factor A , Adipogenesis , Adipose Tissue , Animals , Humans , Mice , Mice, Inbred C57BLABSTRACT
Cryoinjury, or injury due to freezing, is a method of creating reproducible, local injuries in skeletal muscle. This method allows studying the regenerative response following muscle injuries in vivo, thus enabling the evaluation of local and systemic factors that influence the processes of myofiber regeneration. Cryoinjuries are applicable to the study of various modalities of muscle injury, particularly non-traumatic and traumatic injuries, without a loss of substantial volume of muscle mass. Cryoinjury requires only simple instruments and has the advantage over other methods that the extent of the lesion can be easily adjusted and standardized according to the duration of contact with the freezing instrument. The regenerative response can be evaluated histologically by the average maturity of regenerating myofibers as indicated by the cross-sectional areas of myofibers with centrally located nuclei. Accordingly, cryoinjury is regarded as one of the most reliable and easily accessible methods for simulating muscle injuries in studies of muscle regeneration.
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BACKGROUND: Autologous fat grafting (FG) is a popular technique for soft-tissue augmentation, but the fat survival rate is unpredictable. Platelet-rich plasma (PRP) has emerged as an adjuvant to enhance fat graft survival. OBJECTIVES: This literature review and meta-analysis aimed to investigate the effect of PRP on the survival rate of fat grafting. METHODS: A comprehensive systematic literature search was done to identify clinical studies on PRP and fat cotransplantation in PubMed, Cochrane Library, Web of Science, and EMBASE databases up to May 2020. The reference lists of selected articles were reviewed to identify any additional related articles. A meta-analysis was conducted to compare PRP + FG and conventional FG in terms of fat graft survival rate, patient satisfaction rate, and recovery time after surgery. RESULTS: Eleven studies consisting of 1125 patients were analyzed. Patients were followed up from 3 to 24 months post-FG. The fat survival rate varied from 20.5% to 54.8% in FG alone and from 24.1% to 89.2% in the PRP + FG groups. The survival rate was significantly higher and recovery time was significantly lower in the PRP + FG group than in the FG alone group. However, there was no significant difference in the patient satisfaction rate between the groups. CONCLUSIONS: This study demonstrates that PRP-enhanced fat transplantation has better efficacy than conventional fat grafting. Further studies are required to provide the optimum concentration of PRP and the long-term efficacy of the technique. There is not enough evidence to compare the rate of complications with PRP and fat cotransplantation and conventional fat grafting.
Subject(s)
Adipose Tissue/transplantation , Cosmetic Techniques , Plastic Surgery Procedures , Platelet-Rich Plasma , Autografts , Graft Survival , HumansABSTRACT
BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, painful, and severely debilitating inflammatory disease that affects apocrine gland-bearing skin. There is no universal consensus on the management of hidradenitis suppurativa (HS). Current available guidelines are from western countries, which may be of limited use in other parts of the world. In this study, we aim to identify trends in the management of HS in the Middle East (ME) and its differences with the West. METHODS: A systematic literature review was performed to identify all studies in HS management performed by experts in the ME from database inception to June 2020 using PubMed, EMBASE, and Cochrane Library databases. Only original articles published in English language were included. Guidelines from western countries were used for comparison. RESULTS: Fifty-four eligible studies comprising 7649 HS patients from the ME region and nine guidelines from the West were included. No established guidelines were found for the management of HS in the ME. Sex ratio of HS patients in the ME is different in that men reported to be affected at a higher rate than in the West. Different antibiotic regimens were recommended in the ME, and the experts in the ME tend to be more procedure intensive than experts in the West. CONCLUSIONS: Establishing a guideline for HS management in the ME is recommended to address unique considerations in the countries in this region.
Subject(s)
Hidradenitis Suppurativa , Anti-Bacterial Agents/therapeutic use , Consensus , Hidradenitis Suppurativa/diagnosis , Hidradenitis Suppurativa/drug therapy , Hidradenitis Suppurativa/epidemiology , Humans , Male , Middle East/epidemiology , SkinABSTRACT
Poor cellular spreading, proliferation, and infiltration, due to the dense biomaterial networks, have limited the success of most thick hydrogel-based scaffolds for tissue regeneration. Here, inspired by whipped cream production widely used in pastries, hydrogel-based foam bioinks are developed for bioprinting of scaffolds. Upon cross-linking, a multiscale and interconnected porous structure, with pores ranging from few to several hundreds of micrometers, is formed within the printed constructs. The effect of the process parameters on the pore size distribution and mechanical and rheological properties of the bioinks is determined. The developed foam bioinks can be easily printed using both conventional and custom-built handheld bioprinters. In addition, the foam inks are adhesive upon in situ cross-linking and are biocompatible. The subcutaneous implantation of scaffolds formed from the engineered foam bioinks showed their rapid integration and vascularization in comparison with their non-porous hydrogel counterparts. In addition, in vivo application of the foam bioink into the non-healing muscle defect of a murine model of volumetric muscle loss resulted in a significant functional recovery and higher muscle forces at 8 weeks post injury compared with non-treated controls.
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OBJECTIVE: The aim of this study was to determine the extent that appropriate personal protective equipment (PPE), per Centers for Disease Control and Prevention (CDC) guidance, was used during the coronavirus diseases 2019 (COVID-19) pandemic by health-care personnel (HCP) in Louisiana in 5 clinical settings. METHODS: An online questionnaire was distributed to the LA Nursery registry. Appropriate use of PPE in each of the 5 clinical scenarios was defined by the authors based on CDC guidelines. The scenarios ranged from communal hospital space to carrying out aerosol generating procedures (AGPs). A total of 1760 HCP participated between June and July 2020. RESULTS: The average adherence in LA was lowest for the scenario of carrying out AGPs at 39.5% compliance and highest for the scenario of patient contact when COVID-19 not suspected at 82.8% compliance. Adherence among parishes varied widely. Commentary to suggest a shortage of PPE supply and the practice of re-using PPE was strong. CONCLUSIONS: Use of appropriate PPE varied by setting. It was higher in scenarios where only face masks (or respirators) were the standard (ie, community hospital or when COVID-19 not suspected) and lower in scenarios where additional PPE (eg, gloves, eye protection, and isolation gown) was required.
ABSTRACT
Therapeutic strategies that successfully combine two techniques-autologous micrografting and biodegradable scaffolds-offer great potential for improved wound repair and decreased scarring. In this study we evaluate the efficacy of a novel modification of a collagen-glycosaminoglycan (collagen-GAG) scaffold with autologous micrografts using a murine dorsal wound model. db/db mice underwent a full thickness 1.0 cm2dorsal wound excision and were treated with a collagen-GAG scaffold (CGS group), a modified collagen-GAG scaffold (CGS + MG group) or simple occlusive dressing (Blank group). The modified scaffold was created by harvesting full thickness micrografts and transplanting these into the collagen-GAG membrane. Parameters of wound healing, including cellular proliferation, collagen deposition, keratinocyte migration, and angiogenesis were assessed. The group treated with the micrograft-modified scaffold healed at a faster rate, showed greater cellular proliferation, collagen deposition, and keratinocyte migration with higher density and greater maturity of microvessels. The grafts remained viable within the scaffold with no evidence of rejection. Keratinocytes were shown to migrate from the wound border and from the micrograft edges towards the center of the wound, while cellular proliferation was present both at the wound border and wound bed. We report successful treatment of diabetic wounds with a novel collagen-GAG scaffold modified with full-thickness automicrografts. Differences in cellular migration and proliferation offer maiden evidence on the mechanisms of wound healing. Clinically, the successful scaffold engraftment, micrograft viability and improved wound healing offer promising results for the development of a new therapeutic modality for wound repair.