An Engineered Fit-For-Purpose Polymer Nanocomposite Seal Repair Material for Wellbores

Seal integrity of wellbores has become of significant interest due to repeated leakage and spill incidents occurring worldwide that jeopardize both human health and the environment in addition to causing significant economic burden. This is attributed to the fact that wellbores intersecting geographical formations contain potential leakage pathways. The cement-steel and cement-rock formation interfaces are recognized as two critical leakage pathways. A seal repair material that has good bond strength with both steel and rock formations in addition to the ability to completely fill thin microcracks is needed to restore the seal integrity of wellbores. In this research, engineered polymer nanocomposites are proposed for use as seal repair materials for wellbores. Novolac epoxy polymer nanocomposites (PNCs) show more than 200% and 250% higher bond strength with steel and shale, respectively, when compared with microfine cement. In addition, it was found that Novolac epoxy PNCs have up to 545% and 761% higher displacement at peak load and toughness than microfine cement respectively. Moreover, Novolac epoxy PNCs was able to completely fill 800 mm microcracks that microfine cement were not able to completely fill. Microstructural investigations using Fourier-Transform Infrared spectroscopy (FTIR) and Dynamic Mechanical Analysis (DMA) showed that incorporating aluminum nanoparticles (ANPs) in Novolac epoxy PNCs interrupted the polymerization process, which allowed free epoxy groups to improve the bond strength of PNCs with both shale and steel surfaces. On the other hand, penetrability calculations based on contact angle and surface tension of seal repair materials showed that nanomodified methyl methacrylate (NM-MMA) incorporating 0.5 wt.% ANPs has higher potential to penetrate thin microannuli than microfine cement and Novolac epoxy PNCs. NM-MMA was able to seal thin microcracks as small as 30 mm while microfine cement has very limited penetration in such small microcracks. Furthermore, NM-MMA showed more than 1000%, 460%, and 8000% higher apparent bond strength, displacement at failure, and toughness than microfine cement respectively. Microstructural investigation using XRD analysis showed that incorporating ANPs in MMA increased the degree of polymer crystallization enabling significant improvement in polymer ductility, toughness, and reduced creep compliance. A performance study of seal repair materials was evaluated based on their efficiency to seal the cement-steel interface, their ability to withstand cyclic casing pressure, and their ability to withstand harsh environmental conditions. The results showed that microfine cement efficiency was limited to 24%. On the other hand, NM-MMA was able to achieve seal efficiency as high as 103%. Moreover, NM-MMA was able to withstand casing pressure cycles two orders of magnitude higher than microfine cement. Finally, a durability investigation using a weight loss study showed that all PNC seal repair materials have higher resistance to harsh environmental conditions than microfine cement

The effect of synthetic cannabinoids and their combination with TGF-β3 on wound healing of cell cultured human bone cell monolayers and 3D models. The role of synthetic cannabinoid HU308 and HU308/TGF-β3 combinations on cellular adhesion, proliferation, wound healing, nitric oxide, MMP-2 and ECM protein regulation of MG-63 osteoblast monolayers and 3D models

Despite the ongoing political debate regarding the legality of medical marijuana, clinical investigations of the therapeutic use of cannabinoids are now more prevalent than at any time in history. Cannabinoids have been shown to have analgesic, anti-spasmodic, anticonvulsant, anti-tremor, anti-psychotic, anti-inflammatory, anti-oxidant, anti-emetic and appetite-stimulant properties. There are mainly two well-known cannabinoid receptors, CB1 and CB2, located in the central (CB1) and peripheral (CB2) nervous systems as well as the immune system. More recently, endocannabinoids (ligands) and their receptors have also been found in the skeleton which appear as the main body system and physiologically regulated by CB2. This study aimed to examine the effect of both CB1 and CB2 receptor stimulation on wound closure response of MG-63 osteoblast bone cell monolayers using different treatments with cannabinoid such as Winn55,212-2, URB602 and HU308. Also, cell adhesion, cell proliferation and cell length was investigated. The study also aimed to examine the effect of HU308 treatments in combination with TGF-β3 (transforming growth factor beta -3) on wound healing, cell adhesion and extracellular matrix up regulation (collagen type I, fibronectin and protien S-100A6) as well as other biological factors such as secretion of matrix metalloproteinase (MMP-2) and nitric oxide (NO). Finally, this study investigated HU308/TGF-β3 combination treatment on the regulation of extracellular matrix (collagen type I, fibronectin and protien S-100A6) in a 3D multilayer system of MG-63 osteoblast bone cells. Wound healing assays of MG-63 monolayers revealed accelerated wound repair as well as increased cell proliferation mainly regulated through CB2 receptors, and that treatments with HU308 and HU308/TGF-β3 achieved minimum closure timings compared with control groups (P<0.05). Our finding suggested that proliferation rate with 500nM HU308 was significantly higher than control and TGF-β3/HU308 combination groups (P<0.05). Interestingly, percentage of wound remained open after 15 hours for combination groups was 17.6%±1.32 whereas treatment with 500nM HU308 had 20%±2.25 indicating that the combination groups took the lead throughout wound healing. It was also observed that bridge formation in all treatment groups was taking place between 15 to 20 hour periods whereas within control treatments bridge formation started to take place after 25 hours. Cell surface attachment was examined via the trypsinization assay in which the time taken to trypsinize cells from the surface provided a means of assessing the strength of attachment. The results indicated that higher concentrations of HU308 (2μM), induced significant force of cell attachment compared with control and concentrations of 500nM and 1μM (P<0.05). However, groups treated with TGF-β3 and combination HU308/TGF-β3 indicated reduced cell surface attachment compared with control groups, indicating enhanced cell migration. Immunofluorescence staining as well as Elisa based semi-quantification technique indicated that both collagen type I and fibronectin were unregulated using higher concentrations of HU308 with decreased cell proliferation compared to lower concentrations. Nevertheless, protein S-100A6 was up-regulated in treatments with HU308, TGF-β3 and their combination HU308/TGF-β3 (P<0.05), indicating the positive role of these treatments in promoting cell differentiation. MMP-2 levels in the current study were also shown to be concentration-dependent, i.e. higher concentrations of HU308 significantly reduced MMP-2 secretion leading to decreased cell migration, while HU308/TGF-β3 combination treatment increased MMP-2 levels, indicating an increase in cell migration. The current study also examined levels of nitric oxide synthesis in relation to different treatments with HU308, TGF-β3 and HU308/TGF-β3 combination. It was found that nitric oxide up-regulation influences rate of MG-63 osteoblast wound healing in a concentration dependent manner. Lastly, UpCell culture dishes proved to have efficacy in obtaining a multilayer model of MG-63 osteoblast system in-vitro through changes in cell morphology. It was also found that treatments with HU308, TGF-β3 and HU308/TGF-β3 combination influenced collagen type I, fibronecton and protein S-100A6 secretion. These findings supported the earlier Elisa based semi-quantification results obtained for monolayer cultures

Application of topical products to maintain skin integrity in aged and care dependent individuals

Ältere, pflegebedürftige, immobile und schwer kranke Menschen haben ein erhöhtes Risiko, pathologische Hautveränderungen zu entwickeln. Ziel der vorliegenden Arbeit war es, verschiedene präventive topische Ansätze zur Erhaltung und Verbesserung der Hautintegrität im Alter und bei Pflegebedürftigkeit zu untersuchen. Im Rahmen der vorliegenden Dissertation wurde eine systematische Übersichtsarbeit über Wirkung und Effektivität topischer Hautpflegeinterventionen zum Erhalt der Hautintegrität älterer Personen erstellt. Es wurden 63 Volltexte eingeschlossen, die über Behandlungseffekte von Interventionen zur Prävention unerwünschter Hauterscheinungen berichteten. Als unterstützend zur Erhaltung der Hautintegrität älterer Personen erwiesen sich die Verwendung milder Reinigungs und die regelmäßige Applikation rückfettender Pflegeprodukte mit Zusatz von feuchtigkeitsbindenden Substanzen und einem niedrigen pH Wert. In einer explorativen, randomisierten, kontrollierten, klinischen Studie mit Split Body Design wurde die Wirkung eines Basishautpflegeprodukts zur strukturellen Stärkung alternder Haut bei n = 12 älteren Probandinnen (mittleres Alter 70,3 Jahre [SD 2,1]) untersucht. Mittels Saugblasenmethode wurde kontrolliert die Trennung von Dermis und Epidermis induziert und Zeitspannen bis zur Separation als Indikator für die dermo epidermale Adhäsionsstärke verwendet. Nach Applikation des Pflegeprodukts wiesen Interventionsareale längere mediane Zeitspannen bis zur Separation der Hautschichten sowie durchgehend höhere epidermale Hydratationswerte im Vergleich zu den Kontrollarealen auf. Im Einklang mit Ergebnissen der systematischen Übersichtsarbeit zeigt sich, dass die regelmäßige Verwendung eines Basishautpflegeprodukts die dermo epidermale Adhäsion älterer Personen verbessern kann. Die Saugblasenmethode und Messung der Zeitspannen bis zur Separation der Hautschichten stellen einen geeigneten Ansatz zur Quantifizierung der dermo epidermalen Adhäsionsstärke im Rahmen der klinischen Forschung dar. Eine randomisierte, kontrollierte, pragmatische, klinische Studie untersuchte die Wirksamkeit mehrschichtiger Silikonschaumverbände zur Dekubitusprävention bei n = 422 Hochrisikopatienten und patientinnen auf Intensivstationen. Die Verbände wurden in der Interventionsgruppe zusätzlich zu den Standardmaßnahmen der Dekubitusprävention an Sakrum und Fersen appliziert. Die kumulative Dekubitusinzidenz betrug 2,8 % in der Interventions- und 10,5 % in der Kontrollgruppe (Relatives Risiko = 0,26; 95 % Konfidenzintervall [KI] = 0,11 0,62; Absolute Risikoreduktion = 0,08; 95 % KI = 0,03 0,13). Eine Kosten Effektivitäts Analyse wurde durchgeführt und das ermittelte inkrementelle Kosten Effektivitäts Verhältnis lag bei 1945,30€ je vermiedenem Dekubitus in der Interventionsgruppe. Die Applikation der verwendeten Verbände zur Dekubitusprävention an Sakrum und Fersen in der untersuchten Population ist klinisch wirksam und die Verwendung im Sakralbereich kosteneffektiv.Elderly as well as care dependent, immobile, and critically ill individuals have a particularly high risk of developing pathological skin conditions. The aim of this thesis was to investigate different preventive topical interventions to maintain and improve skin integrity in aged and care dependent individuals. In the context of this dissertation, a systematic review about the effects and effectiveness of topical skin care interventions for maintaining skin integrity in the aged population was conducted. Sixty three full text articles were included that reported treatment effects of interventions to prevent unwanted skin conditions. The use of low irritating cleansers and the regular application of humectant containing leave on products with a low pH value were found to support the maintenance of skin integrity in the elderly. Twelve older female subjects (mean age 70.3 years [SD 2.1]) were included in an exploratory, randomized, controlled trial with a split body design to investigate the effect of a basic skin care product on the structural strength of aging skin. By applying the suction blister method, a controlled detachment of the dermis from the epidermis was induced, and the time to separation of the skin layers was used as an indicator for dermo epidermal adhesion strength. After the application of the skin care product, the median time to separation of the skin layers was longer, and skin hydration values were consistently higher in interventional skin areas compared to control areas. Consistent with the results of the systematic review, it appears that regular use of a basic skin care product may improve dermo epidermal adhesion strength in this population. The suction blister method and measurement of time to dermo epidermal separation represent a suitable approach to quantify the dermo epidermal adhesion strength in the context of clinical research. A randomized, controlled, pragmatic, clinical trial in n = 422 high risk intensive care unit patients was performed to investigate the effectiveness of multi layered silicone foam dressings for sacral and heel pressure ulcer prevention in this population. Dressings were applied in addition to standard pressure ulcer prevention care. The cumulative pressure ulcer incidence within the pragmatic trial was 2.8% in the intervention and 10.5% in the control group (relative risk 0.26; 95% confidence interval [CI] 0.11 0.62; absolute risk reduction 0.08; 95% CI 0.03 0.13). A supplementary cost effectiveness analysis was performed and the incremental cost effectiveness ratio was € 1,945.30 per avoided pressure ulcer in the intervention group. The application of the dressings used for pressure ulcer prevention on the sacrum and heels in the population studied is clinically effective and the use in the sacral region is additionally cost effective

The effect of a basic skin care product on the structural strength of the dermo-epidermal junction: An exploratory, randomised, controlled split-body trial

Skin ageing is associated with various structural alterations including a decreased strength of the dermo-epidermal adhesion increasing the risk for shear type injuries (skin tears). Topical applications of basic skin care products seem to reduce skin tear incidence. The suction blister method leads to the artificial and controlled separation of dermis and epidermis. Therefore, time to blister formation may be used as outcome measuring the strength of dermo-epidermal adhesion. We conducted an exploratory, randomised, controlled trial with a split-body design on forearms in healthy female subjects (n = 12; mean age 70.3 [SD 2.1] years). Forearms assigned to the intervention were treated twice daily with petrolatum for 8 weeks. Suction blisters were induced on forearms after 4 and 8 weeks and time to blister formation was measured. Stratum corneum and epidermal hydration were measured and epidermal thickness was assessed via optical coherence tomography. Time to blistering was longer and stratum corneum as well as epidermal hydration was consistently higher in intervention skin areas. We conclude that topical application of basic skin care products may improve mechanical adhesion of the dermo-epidermal junction and that the parameter "time to blistering" is a suitable outcome to measure dermo-epidermal adhesion strength in clinical research. Keywords: prevention; skin care; skin integrity; skin tears; suction bliste

Enhancing SKIN health and safety in aged CARE (SKINCARE Trial): a study protocol for an exploratory cluster-randomized pragmatic trial

Background: Aged long-term care receivers are affected by various adverse skin conditions like pressure ulcers, incontinence-associated dermatitis, dryness, intertrigo, and many more. Prevention of these skin problems and the provision of general hygiene and skin care activities are key areas of nursing practice. Numerous condition-specific guidelines are available and are implemented separately. On the other hand, there is huge overlap in terms of etiology, pathogenesis, and prevention of the skin conditions mentioned above. This leads to fragmented practice neglecting shared etiologies and prevention and treatment principles. Methods: The overall aims of this trial are to test the feasibility and to estimate possible effects of the implementation of a comprehensive skin care and prevention strategy targeting main nursing-relevant skin problems at the same time. A two-arm cluster-randomized controlled trial will be performed in 20 nursing homes randomly selected from the population of nursing homes of the state of Berlin, comparing skin care according to the skin care and prevention strategy with standard skin care. Discussion: It is expected that the implementation of this evidence-based skin care and prevention strategy will reduce the incidence of pressure ulcers, incontinence dermatitis, and other skin problems frequently related to care dependency. This trial will benefit individual patients and aged nursing home residents in general given the high prevalence and incidence of the addressed skin conditions. Findings of this exploratory trial may lay the foundation for a change in the development and evaluation of clinical standards and practices in general as it moves the perspective from individual conditions to a more comprehensive view on overlapping or coexisting health problems, in this case common skin conditions, in old-age long-term care receivers

The effect of a basic skin care product on the structural strength of the dermo‐epidermal junction: An exploratory, randomised, controlled split‐body trial

Skin ageing is associated with various structural alterations including a decreased strength of the dermo-epidermal adhesion increasing the risk for shear type injuries (skin tears). Topical applications of basic skin care products seem to reduce skin tear incidence. The suction blister method leads to the artificial and controlled separation of dermis and epidermis. Therefore, time to blister formation may be used as outcome measuring the strength of dermo-epidermal adhesion. We conducted an exploratory, randomised, controlled trial with a split-body design on forearms in healthy female subjects (n = 12; mean age 70.3 [SD 2.1] years). Forearms assigned to the intervention were treated twice daily with petrolatum for 8 weeks. Suction blisters were induced on forearms after 4 and 8 weeks and time to blister formation was measured. Stratum corneum and epidermal hydration were measured and epidermal thickness was assessed via optical coherence tomography. Time to blistering was longer and stratum corneum as well as epidermal hydration was consistently higher in intervention skin areas. We conclude that topical application of basic skin care products may improve mechanical adhesion of the dermo-epidermal junction and that the parameter "time to blistering" is a suitable outcome to measure dermo-epidermal adhesion strength in clinical research

Cost‐effectiveness of multi‐layered silicone foam dressings for prevention of sacral and heel pressure ulcers in high‐risk intensive care unit patients: An economic analysis of a randomised controlled trial

Pressure ulcer incidence is high in intensive care units. This causes a serious financial burden to healthcare systems. We evaluated the cost-effectiveness of multi-layered silicone foam dressings for prevention of sacral and heel pressure ulcers in addition to standard prevention in high-risk intensive care units patients. A randomised controlled trial to assess the efficacy of multi-layered silicone foam dressings to prevent the development of pressure ulcers on heels and sacrum among 422 intensive care unit patients was conducted. Direct costs for preventive dressings in the intervention group and costs for treatment of incident pressure ulcers in both groups were measured using a bottom-up approach. A cost-effectiveness analysis by calculating the incremental cost-effectiveness ratio using different assumptions was performed. Additional dressing and labour costs of €150.81 (€116.45 heels; €34.36 sacrum) per patient occurred in the intervention group. Treatment costs were €569.49 in the control group and €134.88 in the intervention group. The incremental cost-effectiveness ratio was €1945.30 per PU avoided (€8144.72 on heels; €701.54 sacrum) in the intervention group. We conclude that application of preventive dressings is cost-effective for the sacral area, but only marginal on heels for critically ill patients

The effectiveness of two silicone dressings for sacral and heel pressure ulcer prevention compared with no dressings in high‐risk intensive care unit patients: a randomized controlled parallel‐group trial

Background There is a high incidence of pressure ulcers in high-risk settings such as intensive care. There is emerging evidence that the application of dressings to pressure ulcer predilection areas (sacrum and heels) improves prevention strategies. Objectives To determine whether preventive dressings, applied to the sacrum and heels of high-risk patients in intensive care units, in addition to standard prevention, reduces the incidence of pressure ulcers. Methods Between June 2015 and July 2018, a randomized, controlled, two-arm, superiority pragmatic study was performed with a concealed 1 : 1 allocation to the intervention and control group. Patients assigned to the intervention group had dressings applied to the sacrum and heels. Results In total, 7575 patients were screened for eligibility and 475 patients were included and allocated to both groups. Finally, 212 patients in the intervention group and 210 in the control group were analysed. The mean age was 63 center dot 5 years and the majority of patients were male (65 center dot 4%). The cumulative pressure ulcer incidence category II and above was 2 center dot 8% in the intervention, and 10 center dot 5% in the control group (P = 0 center dot 001). Compared with the control group, the relative risk in the intervention group was 0 center dot 26 [95% confidence interval (CI) 0 center dot 11-0 center dot 62] and the absolute risk reduction was 0 center dot 08 (95% CI 0 center dot 03-0 center dot 13). Conclusions The results indicate that the application of dressings, in addition to standard prevention, in high-risk intensive care unit patients is effective in preventing pressure ulcers at the heels and sacrum. What's already known about this topic? Pressure ulcers are severe soft tissue injuries and wounds, which occur worldwide in all healthcare settings. Despite preventive interventions, pressure ulcers still develop. There is emerging evidence that dressings help to prevent pressure ulcers. What does this study add? The incidence of pressure ulcers in intensive care units among high-risk patients remains high. The application of dressings to the sacrum and heels, in addition to standard preventive measures, reduces the relative and absolute risks for the development of pressure ulcers. The application of preventive dressings at the heels and sacrum seems to be feasible in intensive care settings

The effect of WIN55, 212-2 on protein S100, matrix metalloproteinase-2 and nitric oxide expression of chondrocyte monolayer

YesStudies have been conducted to highlight the anti-inflammatory and immunosuppressive properties of synthetic cannabinoids as well as their potential for cartilage repair. Various wound healing techniques can be used to investigate the mechanisms of chondrocyte repair in monolayers or three dimensional tissues constructs. In this work the effect of WIN55, 212-2 (WIN-2) on nitric oxide (NO) and matrix metalloproteinase-2 (MMP-2) expressed by wounded chondrocyte monolayers was investigated. Moreover, expression of collagen type-I and type-II, fibronectin and S100 proteins were detected using immunofluorescence and quantitatively verified using ELISA based techniques following treatment with 1 μM and 2 μM of WIN-2. Treating chondrocytes with 1 μM of WIN-2 significantly increased expression of collagen type-II, fibronectin and S100, and significantly reduced collagen type-I expressions as compared to the control groups. On the other hand, both concentrations of WIN-2 significantly reduced the expression of the inflammation markers NO and MMP-2 in a dose dependent manner. These findings highlight the potential use of the synthetic cannabinoids for improving cartilage healing properties as well as acting as an anti-inflammatory agent which could be used to enhance tissue engineering protocols aimed at cartilage repair