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PURPOSE: The duties of paramedics and emergency medical technicians (P&EMTs) are continuously changing due to developments in medical systems. This study presents evaluation goals for P&EMTs by analyzing their work, especially the tasks that new P&EMTs (with less than 3 years' experience) find difficult, to foster the training of P&EMTs who could adapt to emergency situations after graduation. METHODS: A questionnaire was created based on prior job analyses of P&EMTs. The survey questions were reviewed through focus group interviews, from which 253 task elements were derived. A survey was conducted from July 10, 2023 to October 13, 2023 on the frequency, importance, and difficulty of the 6 occupations in which P&EMTs were employed. RESULTS: The P&EMTs' most common tasks involved obtaining patients' medical histories and measuring vital signs, whereas the most important task was cardiopulmonary resuscitation (CPR). The task elements that the P&EMTs found most difficult were newborn delivery and infant CPR. New paramedics reported that treating patients with fractures, poisoning, and childhood fever was difficult, while new EMTs reported that they had difficulty keeping diaries, managing ambulances, and controlling infection. CONCLUSION: Communication was the most important item for P&EMTs, whereas CPR was the most important skill. It is important for P&EMTs to have knowledge of all tasks; however, they also need to master frequently performed tasks and those that pose difficulties in the field. By deriving goals for evaluating P&EMTs, changes could be made to their education, thereby making it possible to train more capable P&EMTs.
Subject(s)
Allied Health Personnel , Clinical Competence , Educational Measurement , Emergency Medical Technicians , Humans , Emergency Medical Technicians/education , Republic of Korea , Surveys and Questionnaires , Allied Health Personnel/education , Educational Measurement/methods , Female , Male , Focus Groups , Adult , Emergency Medical Services , Cardiopulmonary Resuscitation/education , Communication , ParamedicsABSTRACT
Polylactic acid (PLA) and polybutylene succinate (PBS) are gaining prominence as environmentally friendly alternatives to petroleum-based polymers due to their inherent biodegradability. For their textile applications, this research is focused on exploring the effects of PBS content on the rheological properties of PLA/PBS blends and the characteristics of PLA/PBS blend fibers. PLA/PBS blends and fibers with varying PBS contents (0 to 10 wt.%) were prepared using melt-blending and spinning methods. Uniform morphologies of the PLA/PBS blends indicated that PBS was compatible with PLA, except at 10% PBS content, where phase separation occurred. The introduction of PBS reduced the complex viscosity of the blends, influencing fiber properties. Notably, PLA/PBS fibers with 7% PBS exhibited improved crystallinity, orientation factor, and elasticity (~16.58%), with a similar tensile strength to PLA fiber (~3.58 MPa). The results suggest that an optimal amount of PBS enhances alignment along the drawing direction and improves the molecular motion in PLA/PBS blend fiber. This study highlights the potential of strategically blending PBS to improve PLA fiber characteristics, promising advancement in textile applications.
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BACKGROUND: Typhoid Fever remains a major cause of morbidity and mortality in low-income settings. The Severe Typhoid in Africa programme was designed to address regional gaps in typhoid burden data and identify populations eligible for interventions using novel typhoid conjugate vaccines. METHODS: A hybrid design, hospital-based prospective surveillance with population-based health-care utilisation surveys, was implemented in six countries in sub-Saharan Africa. Patients presenting with fever (≥37·5°C axillary or ≥38·0°C tympanic) or reporting fever for three consecutive days within the previous 7 days were invited to participate. Typhoid fever was ascertained by culture of blood collected upon enrolment. Disease incidence at the population level was estimated using a Bayesian mixture model. FINDINGS: 27â866 (33·8%) of 82â491 participants who met inclusion criteria were recruited. Blood cultures were performed for 27â544 (98·8%) of enrolled participants. Clinically significant organisms were detected in 2136 (7·7%) of these cultures, and 346 (16·2%) Salmonella enterica serovar Typhi were isolated. The overall adjusted incidence per 100â000 person-years of observation was highest in Kavuaya and Nkandu 1, Democratic Republic of the Congo (315, 95% credible interval 254-390). Overall, 46 (16·4%) of 280 tested isolates showed ciprofloxacin non-susceptibility. INTERPRETATION: High disease incidence (ie, >100 per 100â000 person-years of observation) recorded in four countries, the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with measures designed to improve clean water, sanitation, and hygiene practices. FUNDING: The Bill & Melinda Gates Foundation.
Subject(s)
Typhoid Fever , Vaccines , Humans , Typhoid Fever/epidemiology , Typhoid Fever/prevention & control , Ghana , Madagascar , Burkina Faso/epidemiology , Ethiopia , Incidence , Nigeria , Prospective Studies , Bayes Theorem , Democratic Republic of the CongoABSTRACT
Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age-related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in Cpne7-null dental pulp, odontoblast survival is impaired, and aberrant dentin is extensively formed. Intraperitoneal or topical application of CPNE7-derived functional peptide, however, alleviates the DNA damage accumulation and rescues the pathologic dentin phenotype. Notably, a healthy dentin-pulp complex lined with metabolically active odontoblasts is observed in 23-month-old Cpne7-overexpressing transgenic mice. Furthermore, physiologic dentin was regenerated in artificial dentinal defects of Cpne7-overexpressing transgenic mice. Taken together, Cpne7 is indispensable for the maintenance and homeostasis of odontoblasts, while promoting odontoblastic differentiation of the progenitor cells. This research thereby introduces its potential in oral disease-targeted applications, especially age-related dental diseases involving dentinal loss.
Subject(s)
Aging, Premature , Mice , Animals , Dental Pulp , Cellular Senescence/genetics , Odontoblasts , Cell Differentiation/genetics , Mice, TransgenicABSTRACT
Objective: Mitochondrial dysfunction affects hepatic lipid homeostasis and promotes ROS generation. Copine7 (CPNE7) belongs to the ubiquitous copine family of calcium-dependent phospholipid binding proteins. CPNE7 has a high calcium ion binding affinity and the capacity to scavenge reactive oxygen species (ROS). A recent study reported that abnormalities in fatty acid and lipid metabolism were linked to the gene variant of CPNE7. Therefore, the purpose of this study is to examine the role of Cpne7 in hepatic lipid metabolism based on mitochondrial function. Methods: Lipid metabolism, mitochondrial function, and ROS production were investigated in high-fat diet (HFD)-fed Cpne7-/- mice and H2O2-damaged HepG2 hepatocytes following CPNE7 silencing or overexpression. Results: Cpne7 deficiency promoted severe hepatic steatosis in the HFD-induced NAFLD model. More importantly, mitochondrial dysfunction was observed along with an imbalance of mitochondrial dynamics in the livers of HFD-fed Cpne7-/-mice, resulting in high ROS levels. Similarly, CPNE7-silenced HepG2 hepatocytes showed high ROS levels, mitochondrial dysfunction, and increased lipid contents. On the contrary, CPNE7-overexpressed HepG2 cells showed low ROS levels, enhanced mitochondrial function and decreased lipid contents under H2O2-induced oxidative stress. Conclusions: In the liver, Cpne7 deficiency causes excessive ROS formation and mitochondrial dysfunction, which aggravates lipid metabolism abnormalities. These findings provide evidence that Cpne7 deficiency contributes to the pathogenesis of NAFLD, suggesting Cpne7 as a novel therapeutic target for NAFLD.
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Particulate matter (PM) exposure can adversely affect respiratory function. Probiotics can alleviate the inflammatory responses in respiratory diseases. We examined the protective effects of Lactobacillus paracasei ATG-E1 isolated from the feces of a newborn baby against airway inflammation in a PM10 plus diesel exhaust particle (DEP) (PM10D)-induced airway inflammation model. BALB/c mice were exposed to PM10D by intranasal injection three times at 3-day intervals for 12 days, and L. paracasei ATG-E1 was administered orally for 12 days. Analysis of immune cell population and expression of various inflammatory mediators and gut barrier-related genes were determined in bronchoalveolar lavage fluid (BALF), lung, peyer's patch, and small intestine. A histological analysis of the lungs was performed. In addition, the in vitro safety and their safety in genomic analyses were examined. L. paracasei ATG-E1 was found to be safe in vitro and by genomic analysis. L. paracasei ATG-E1 suppressed neutrophil infiltration and the number of CD4+, CD4+CD69+, CD62L-CD44+high, CD21/35+B220+, and Gr-1+CD11b+ cells, as well as the expression of inflammatory mediators, including chemokine (C-X-C motif) ligand (CXCL)-1, macrophage inflammatory protein (MIP)-2, interleukin (IL)-17a, tumor necrosis factor (TNF)-α, and IL-6 in BALF and lungs in PM10D-induced airway inflammation. It protected against histopathological damage in the lungs of mice with PM10D-induced airway inflammation. L. paracasei ATG-E1 concomitantly increased the expression levels of the gut barrier function-related genes occludin, claudin-1, and IL-10 in the small intestine, with an increased number of CD4+ and CD4+CD25+ immune cells in the peyer's patch. L. paracasei ATG-E1 suppressed immune activation and airway inflammatory responses in the airways and lungs by restoring the lung damage by PM10D. It also regulated intestinal immunity and ameliorated the gut barrier function in the ileum. These results indicate the potential of L. paracasei ATG-E1 as an protective and therapeutic agent against airway inflammation and respiratory diseases.
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INTRODUCTION: Cholera remains a significant contributor to diarrhoeal illness, especially in sub-Saharan Africa. Few studies have estimated the cost of illness (COI) of cholera in Malawi, a cholera-endemic country. The present study estimated the COI of cholera in Nsanje, southern Malawi, as part of the Cholera Surveillance in Malawi (CSIMA) programme following a mass cholera vaccination campaign in 2015. METHODS: Patients ≥12 months of age who were recruited as part of CSIMA were invited to participate in the COI survey. The COI tool captured household components of economic burden, including direct medical and non-medical costs, and indirect lost productivity costs. RESULTS: Between April 2016 and March 2020, 40 cholera cases were enrolled in the study, all of whom participated in the COI survey. Only two patients had any direct medical costs and five patients reported lost wages due to illness. The COI per patient was US$14.34 (in 2020), more than half of which was from direct non-medical costs from food, water, and transportation to the health centre. CONCLUSION: For the majority of Malawians who struggle to subsist on less than US$2 a day, the COI of cholera represents a significant cost burden to families. While cholera treatment is provided for free in government-run health centres, additional investments in cholera control and prevention at the community level and financial support beyond direct medical costs may be necessary to alleviate the economic burden of cholera on households in southern Malawi.
Subject(s)
Cholera , Cholera/epidemiology , Cholera/prevention & control , Cost of Illness , Family Characteristics , Humans , Malawi/epidemiology , Prospective StudiesABSTRACT
In this study, highly porous carbon fiber was prepared for hydrogen storage. Porous carbon fiber (PCF) and activated porous carbon fiber (APCF) were derived by carbonization and chemical activation after selectively removing polyvinyl alcohol from a bi-component fiber composed of polyvinyl alcohol and polyacrylonitrile (PAN). The chemical activation created more pores on the surface of the PCF, and consequently, highly porous APCF was obtained with an improved BET surface area (3058 m2 g-1) and micropore volume (1.18 cm3 g-1) compare to those of the carbon fiber, which was prepared by calcination of monocomponent PAN. APCF was revealed to be very efficient for hydrogen storage, its hydrogen capacity of 5.14 wt% at 77 K and 10 MPa. Such hydrogen storage capacity is much higher than that of activated carbon fibers reported previously. To further enhance hydrogen storage capacity, catalytic Pd nanoparticles were deposited on the surface of the APCF. The Pd-deposited APCF exhibits a high hydrogen storage capacity of 5.45 wt% at 77 K and 10 MPa. The results demonstrate the potential of Pd-deposited APCF for efficient hydrogen storage.
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Biotransformation, the structural modification of chemical compounds, has proved to be an indispensable tool in providing beneficial health effects. Although the health benefits of biotransformation using plant sources has been widely studied, the anti-adipogenic effect of biotransformed dairy products, such as whey, have not yet been demonstrated. Here, we investigated the anti-adipogenic effect of whey biotransformed by Weissella cibaria in 3T3-L1 adipocytes. Weissella cibaria-biotransformed whey considerably reduced the accumulation of lipid droplets and intracellular triglycerides in 3T3-L1 cells. In the presence of W. cibaria-biotransformed whey, the mRNA and protein expression of a key transcription factor, peroxisome proliferator-activated receptor γ (PPARγ), for adipogenesis was markedly suppressed in 3T3-L1 cells. Additionally, W. cibaria-biotransformed whey also decreased the mRNA and protein expressions of lipoprotein lipase and adipocyte fatty acid-binding protein, which are regulated by PPARγ. Moreover, W. cibaria-biotransformed whey inhibited the expression of adipokines, resistin, and leptin. Collectively, these results suggest that whey biotransformed by W. cibaria has the potential to exert anti-adipogenic effects by inhibiting intracellular signaling events of adipogenic-related transcription factors and target genes.
Subject(s)
Adipogenesis , Whey , 3T3-L1 Cells , Adipocytes/metabolism , Animals , Biotransformation , Cell Differentiation , Mice , PPAR gamma/genetics , PPAR gamma/metabolism , Weissella , Whey/metabolismABSTRACT
Microbial bioconversion using lactic acid bacteria (LAB) provides several human health benefits. Although whey and whey-derived bioactive compounds can contribute to an improvement in human health, the potential anti-obesity effect of whey bioconversion by LAB has not been well studied. This study aimed to investigate whether bioconversion of whey by Pediococcus pentosaceus KI31 and Lactobacillus sakei KI36 (KI31-W and KI36-W, respectively) inhibits 3T3-L1 preadipocyte differentiation. Both KI31-W and KI36-W reduced intracellular lipid accumulation significantly, without decreasing 3T3-L1 preadipocyte proliferation. In addition, obesity-related transcription factor (peroxisome proliferator-activated receptor γ) and genes (adipocyte fatty acid-binding protein and lipoprotein lipase) were down-regulated significantly in 3T3-L1 cells in the presence of KI31-W and KI36-W. Collectively, these results suggest that bioconversion of whey by LAB exhibits anti-adipogenic activity and may be applied as a therapeutic agent for obesity.
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Objective: To test the effectiveness of electroacupuncture (EA) for managing intractable neuropathic pain (NeP) and assess the protocol for a larger confirmatory trial. Design: A prospective, multicenter, single-armed, add-on, pilot study. Settings/location: At two tertiary university-based hospitals in Seoul, Republic of Korea. Subjects: Patients with chronic peripheral NeP, who have received conventional oral medications but complained of moderate to severe pain. Interventions: Two Korean medicine doctors conducted 12 sessions of EA (2 sessions per week for 4 weeks, followed by 1 session per week for the second month) in addition to conventional treatment. Outcome measures: During the 8-week treatment period, pain intensity, pain natures such as burning, electric shock-like, temperature or mechanical hyperalgesia, and numbness, Short Form of the McGill Pain Questionnaire (SF-MPQ) and the Brief Pain Inventory (BPI-SF), the EuroQol five dimensions questionnaire, patients' satisfaction, and adverse events were evaluated. The primary endpoint was a change in pain intensity (%) at 4 weeks from the baseline. Results: Among 22 patients, 19 finished the protocol. The eight EA sessions over a month reduced pain intensity from 6.0 ± 1.6 at baseline to 3.2 ± 0.9 at 4 weeks, which was a 46.7% reduction (p < 0.001). The incidences of severe burning, electric shock-like pain, and mechanical hyperalgesia reduced at 8 weeks [36%-16% (p = 0.04), 53%-21% (p = 0.009), and 53%-26% (p = 0.03), respectively]. The affective dimensions in the SF-MPQ (p = 0.007) and the pain interference parameters, including mood (p = 0.02), relations with other people (p = 0.03), and enjoyment of life (p = 0.002) in the BPI-SF, were improved at 4 and 8 weeks. The majority of patients (68%) responded that their pain was "much or somewhat improved." Overall, 84.2% expressed "satisfaction" with their multidisciplinary management. Conclusions: EA might decrease the intensity of NeP, in particular, such as burning, electric shock-like pain, and mechanical hyperalgesia, which was accompanied by psychosocial and functional improvement. A larger study is warranted to prove the effectiveness of EA for managing refractory NeP. Trial registration: ClinicalTrials.gov: NCT03315598. Retrospectively registered on October 20, 2017.
Subject(s)
Electroacupuncture , Neuralgia/therapy , Pain Management/methods , Aged , Chronic Pain/therapy , Female , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Republic of KoreaABSTRACT
OBJECTIVE: Temporomandibular joint disorder (TMD) requires long-term management and can be a financial burden for patients. Here, we investigated the treatment received by people diagnosed with TMD and its relevant costs. DESIGN: A descriptive, cross-sectional study. SETTING AND PARTICIPANTS: We performed secondary data analysis of health insurance claims data provided by the Health Insurance Assessment and Review (HIRA) of the Republic of Korea. We reviewed the records of 10 041 patients who were diagnosed with TMD and who utilised outpatient healthcare service at least once between January and December 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: Data on use of medical services, hospitalisations, sociodemographic factors, treatment and medication were retrieved and analysed. Cost was defined as the cost of care incurred by a health insurance beneficiary at a care facility. RESULTS: We reported the characteristics as medians, frequencies and percentages and found that most TMD patients were outpatients, women (58.9%) and in their 20s (46.4%). For visit type, 85.9% of all patients had an outpatient dental medical visit, with most visiting dental clinics and dental hospitals. Western medicine (WM; 9.8%) was prescribed more often, followed by Korean medicine (KM; 8.2%). The median expense per patient was highest among those in their 20s (58.00, 23.90, 53.40, 65.90 US$ for overall, WM, dental medicine (DM) and KM, respectively). Consultation fees accounted for the greatest percentage (42.8%) of DM and WM care expenses, while injection/non-surgical intervention fees accounted for the greatest percentage of KM care expenses. The most commonly used treatments for TMD were temporomandibular joint stimulation therapy (51.1%) and acupuncture (19.9%), considered as the most basic care for TMD. Psychosomatic agents (86.4%) were the most commonly used medications in outpatients. CONCLUSIONS: While people with TMD most commonly received temporomandibular stimulation therapy, the costs and duration of treatment varied significantly for these patients.
Subject(s)
Temporomandibular Joint Disorders , Cross-Sectional Studies , Female , Health Services , Humans , Insurance, Health , Republic of Korea , Temporomandibular Joint Disorders/therapyABSTRACT
BACKGROUND: Angiogenesis is essential for the optimal functioning of orthopedic medical implants. Protein functionalization of implant surfaces can improve tissue integration through proper vascularization and prevent implant failure in patients lacking sufficient angiogenesis. OBJECTIVE: The aim of this study was to evaluate the angiogenic activity of titanium surfaces functionalized with recombinant VE-cadherin extracelluar1-4 (VE-CADEC1-4) protein in human umbilical vein endothelial cells (HUVECs). METHODS: After titanium discs were coated with recombinant VE-CADEC1-4 protein at appropriate concentrations, the behavior of HUVECs on the VE-CADEC1-4-functionalized titanium discs were evaluated by cell adhesion assay, proliferation assay, and real-time RT-PCR. RESULTS: Recombinant VE-CADEC1-4-functionalized titanium surfaces improved the adhesion of HUVECs by 1.8-fold at the optimal concentration, and the proliferative activity was 1.3-fold higher than the control at 14 days. In addition, when angiogenesis markers were confirmed by real-time RT-PCR, PECAM-1 increased approximately 1.2-fold, TEK approximately 1.4-fold, KDR approximately 1.6-fold, and Tie-1 approximately 2.1-fold compared to the control. CONCLUSION: Recombinant VE-CADEC1-4-functionalized titanium surfaces improved cell adhesion, proliferation, and angiogenic differentiation of HUVECs, suggesting that the VE-CADEC1-4-functionalization of titanium surfaces can offer angiogenic surfaces with the potential to improve bone healing in orthopedic applications.
Subject(s)
Antigens, CD , Cadherins , Cell Proliferation/drug effects , Coated Materials, Biocompatible , Human Umbilical Vein Endothelial Cells/metabolism , Titanium , Antigens, CD/chemistry , Antigens, CD/pharmacology , Cadherins/chemistry , Cadherins/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Human Umbilical Vein Endothelial Cells/cytology , Humans , Protein Domains , Titanium/chemistry , Titanium/pharmacologyABSTRACT
Extracellular matrix (ECM) including fibronectin (FN) and elastin plays a pivotal role in providing a microenvironment to support tissue regeneration in stem cell therapy. To develop a novel biomimetic ECM for stem cell differentiation, we engineered FN type III 9 and 10 domains fused to elastin-like polypeptides (FN-ELPs). The recombinant FN-ELP fusion protein was expressed in Escherichia coli and purified by inverse transition cycling. Human mesenchymal stem cells (hMSCs) cultured on plates coated with FN-ELP had significantly greater adhesion activity and proliferation than cells grown on non-coated plates. FN-ELP induced the osteogenic differentiation by elevating alkaline phosphatase (ALP) and mineralization activity of hMSCs. Furthermore, the osteogenic marker gene expressions of ALP, collagen type I (Col I), osteopontin (OPN), and transcriptional coactivator with a PDZ-binding motif (TAZ) were increased in hMSCs cultured on plates coated with FN-ELP. We reported a novel biomimetic ECM with potential for bone regeneration that promotes the osteogenic differentiation of hMSCs.
Subject(s)
Elastin/chemistry , Fibronectin Type III Domain , Fibronectins/chemistry , Mesenchymal Stem Cells/cytology , Osteogenesis/drug effects , Peptides/chemistry , Biomimetics , Cell Differentiation , Cell Proliferation , Cells, Cultured , Collagen Type I/metabolism , Humans , Osteopontin/metabolism , Protein Domains , Protein Engineering , Recombinant Proteins , Regeneration , Trans-Activators/metabolism , Transcriptional Coactivator with PDZ-Binding Motif ProteinsABSTRACT
In this study, the morphological effects of ZnO on the antimicrobial and deodorant activities of synthetic fibers were investigated. Three different polyethylene terephthalate (PET)/ZnO filaments were prepared by incorporating various ZnO nanostructures (rods, plates, and spheres) into PET filaments via a melt-spinning process. The antimicrobial activity of the as-prepared fibers was evaluated by the shake-flask method using two types of bacteria (Staphylococcus aureus and Klebsiella pneumoniae). The deodorant activity of the as-prepared fibers was evaluated by the gas detection tube method. All the PET/ZnO filaments exhibited excellent antimicrobial activity with a bacterial reduction value of 99.9%. The PET/ZnO rod filament showed the best deodorant performance of 60.0%. Both the antimicrobial and deodorant activities of the PET/ZnO filaments were influenced by the morphology of ZnO. However, the morphology of ZnO had a different effect on each functionality of the PET/ZnO filaments. The antimicrobial activity of the PET/ZnO filaments was mainly affected by the physical properties of ZnO rather than its morphology. By contrast, the deodorant activity of the PET/ZnO filaments was highly influenced by the morphology of ZnO.
Subject(s)
Anti-Infective Agents , Deodorants , Zinc Oxide , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Polyethylene Terephthalates/pharmacology , Zinc Oxide/pharmacologyABSTRACT
BACKGROUND: Laminin, a member of the Extracellular Matrix (ECM), is a glycoprotein that is used as a factor that affects cell adhesion, proliferation, survival, and differentiation. Of these, five globular domains (LG domains) of the alpha chain play an important role in influencing the cell by binding to the integrin. OBJECTIVE: This study aimed to evaluate the ability of globular domains 1-3 of laminin alpha2 (rhLAMA2LG1-3) in maintaining the pluripotency of human Mesenchymal Stem Cells (hMSCs), which are widely used in regenerative medicine. METHODS: hMSCs were grown in the medium supplemented with rhLAMA2LG1-3, then the effect of the protein on hMSCs were confirmed through cell adhesion assay, proliferation assay and RTPCR. RESULTS: rhLAMA2LG1-3 expressed in Escherichia coli has a molecular weight of 70 kDa, at 1 µg/ml concentration of rhLAMA2LG1-3, the attachment and proliferation of hMSCs were approximately 3.18-fold and 1.67-fold, respectively, more efficient than those of untreated controls. In addition, the undifferentiated state and degree of stemness of hMSCs were measured, on the basis of CD90 and CD105 levels. In the rhLAMA2LG1-3-treated hMSCs, the expression levels of CD90 and CD105 increased by 2.83-fold and 1.62-fold, respectively, compared to those in untreated controls. CONCLUSIONS: rhLAMA2LG1-3 can be potentially used in stem cell therapy to improve the viability and maintain the undifferentiated state of hMSCs.
Subject(s)
Extracellular Matrix/metabolism , Laminin/metabolism , Mesenchymal Stem Cells/metabolism , Recombinant Proteins/metabolism , Cell Adhesion , Cell Proliferation , Cells, Cultured , DNA, Complementary/metabolism , Escherichia coli , Humans , Laminin/genetics , Protein Domains , Recombinant Proteins/geneticsABSTRACT
PURPOSE: To demonstrate the advantages and efficacy of an air-perfused membrane dissection to control intraoperative bleeding in 23-gauge sutureless vitrectomy for proliferative diabetic retinopathy with severe fibrovascular membranes. Meterials and Methods: A prospective, consecutive, interventional case series of 15 eyes that underwent air-perfused diabetic vitrectomy (air vitrectomy group) for removal of the membranes was compared with a retrospective, membrane-matched case series of 10 eyes that underwent conventional diabetic vitrectomy (conventional vitrectomy group). The main outcome measures were real vitrectomy time, intraoperative and postoperative complications, and anatomic and functional successes at the final examination. RESULTS: The incidence of intraoperative retinal tears was 30% (3/10 eyes) in the conventional vitrectomy group and 20% (3/15 eyes) in the air vitrectomy group (p > 0.05). The postoperative complications such as vitreous hemorrhage or tractional retinal detachment were not common in both groups during the 6-month follow-up (p > 0.05). In addition, the final anatomic and functional success rates did not differ significantly between the groups (p > 0.05). However, the vitrectomy time was significantly shorter in the air vitrectomy group (67.0 ± 21.8 min) than in the conventional group (84.6 ± 21.1 min) (p = 0.04). CONCLUSION: Air-perfused vitrectomy showed comparable anatomic and functional success rates and shorter surgical time, compared with conventional vitrectomy in diabetic eyes with severe fibrovascular membranes. We suppose that the shortened surgical time in the air vitrectomy group is related to less intraoperative bleeding and more efficient hemostasis.
Subject(s)
Air , Diabetic Retinopathy/surgery , Endotamponade , Epiretinal Membrane/surgery , Intraoperative Complications , Vitrectomy/methods , Vitreous Hemorrhage/prevention & control , Adult , Female , Humans , Male , Middle Aged , Operative Time , Postoperative Complications , Prospective StudiesABSTRACT
CKD-519, a potent cholesteryl ester transfer protein (CETP) inhibitor, is a clinical candidate being developed for the treatment of dyslipidemia. It is considered a Biopharmaceutical Classification System II compound with low solubility and high permeability. The objective of this study was to develop early formulations focusing on the dissolution rate of the compound to achieve dose-dependent exposure. High performance formulation strategies including solid dispersion (SD) and a self-microemulsifying drug delivery system (SMEDDS) were investigated and their in vivo and in vitro correlations were also evaluated in monkeys along with dose optimization in human volunteers. The SD granules were prepared in a fluid bed granulator using microcrystalline cellulose and mannitol as carriers. Poloxamer 407 and Eudragit E PO were each found to be a suitable solubilizing agent and polymer for the improvement of the CKD-519 dissolution rate. Pharmacokinetic studies in monkeys showed that the SD tablets exhibited better absorption than the SMEDDS in a dose-dependent manner from 1.5â¯mg to 100â¯mg. The mannitol-based SD tablet formulations were bioequivalent. However, pharmacokinetics studies in humans showed that the dose was saturable above 100â¯mg of CKD-519. This study was performed to determine how to develop early formulations for clinical studies and to identify rational formulation development strategies for CKD-519 to establish the pharmaceutical proof-of-concept in humans.
Subject(s)
Anticholesteremic Agents/administration & dosage , Cholesterol Ester Transfer Proteins/antagonists & inhibitors , Drug Development/methods , Hydrocarbons, Fluorinated/administration & dosage , Oxazoles/administration & dosage , Administration, Oral , Adult , Animals , Anticholesteremic Agents/chemistry , Anticholesteremic Agents/pharmacokinetics , Biological Availability , Cellulose/chemistry , Cholesterol Ester Transfer Proteins/metabolism , Double-Blind Method , Drug Carriers , Drug Compounding , Excipients/chemistry , Female , Humans , Hydrocarbons, Fluorinated/chemistry , Hydrocarbons, Fluorinated/pharmacokinetics , Macaca mulatta , Male , Mannitol/chemistry , Middle Aged , Models, Biological , Oxazoles/chemistry , Oxazoles/pharmacokinetics , Permeability , Poloxamer/chemistry , Polymethacrylic Acids/chemistry , Proof of Concept Study , Solubility , Tablets , Young AdultABSTRACT
PURPOSE: To evaluate macular photostress and visual experience between coaxial microscope illumination versus oblique intracameral illumination during cataract surgery. SETTING: Gachon University Gil Hospital, Incheon, South Korea. DESIGN: Prospective case series. METHODS: Consecutive patients who had cataract surgery using microscope illumination and intracameral illumination were included. The patients were asked to complete a questionnaire (seeing strong lights, feeling photophobia, feeling startled (fright) when seeing lights, seeing any colors, seeing any instruments or surgical procedures, and estimating intraoperative visual function) designed to describe their cataract surgery experience. The images projected on the retina of the model eye (rear view) with artificial opaque fragments in the anterior chamber during simulating cataract surgery were compared between the 2 illumination types. RESULTS: Sixty patients completed the questionnaire. Scores for strong lights, photophobia, fright, and color perception were significantly higher with microscope illumination than with intracameral illumination (all P < .001). More patients preferred the intracameral illumination (45 [75.0%]) to the microscope illumination (13 [21.7%]). In the rear-view images created in a model eye, only the bright microscope light in the center was seen without any lens image in the microscope illumination. However, in the intracameral illumination, the less bright light from the light pipe in the periphery and the lens fragments were seen more clearly. CONCLUSIONS: In a view of the patients' visual experience, oblique intracameral illumination caused less subjective photostress and was preferred over coaxial microscope illumination. Objective findings from the model-eye experiment correlated to the result of visual experience.