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The dynamics of high-pressure gas flow injected through a nozzle during a thermal cutting process has an important effect on cutting performance. In this study, an actual gas flow condition inside a cut kerf of a plasma cut sample was simulated by considering various geometric features of the cut kerf, such as kerf width difference and cutting length difference between the top and bottom surfaces. A prototype cut kerf shape was fabricated using a transparent material. A gas flow shadowgraph from inside the fabricated cut kerf was observed using the Schlieren method. In addition, image processing was performed on images obtained with the Schlieren method before and after gas injection, which were used to validate the numerical simulation models. The effect of turbulent viscosity in various turbulent models was studied using computational fluid dynamics analyses. The results confirmed that the k–ω turbulent model was the most suitable turbulent model for the geometry used in this study. The simulation results for this model were qualitatively consistent with the reported experimental measurements.

Laser shock peening creates compressive residual stress on the surface of the material, reducing stress corrosion cracking and increasing fatigue life. FE simulation of laser shock peening is an effective way to determine the mechanical effects on the material. In conventional FE simulations of laser shock peening, explicit analysis is used while pressure loads are applied and switched into implicit analysis to dissipate kinetic energy. In this study, static damping was adopted to dissipate kinetic energy without conversion into implicit analysis. Simulation of a single laser shock and multiple shocks was performed, and deformation and minimum principal stress were compared to evaluate the static damping effect. The history of the internal and kinetic energy were analyzed to compare the stabilization time depending on the damping value. Laser shock peening experiments were also performed on stainless steel 304 material. The residual stress of the specimen was measured by the hole drilling method and it was compared to the FE simulation result. The residual stress from the experiment and the simulation results showed similar distributions in the depth direction. Anisotropic residual stress distribution due to the laser path was observed in both results.

Abstract Background The purpose of the Korean Hip Fracture Registry (KHFR) Study is to establish a nationwide, hospital-based prospective cohort study of adults with hip fracture to explore the incidence and risk factors of second osteoporotic fractures for a Fracture Liaison Service (FLS) model. Methods The KHFR, a prospective multicenter longitudinal study, was launched in 2014. Sixteen centers recruited participants who were treated for hip fracture. The inclusion criteria were patients, who were treated for proximal femur fracture due to low-energy trauma and aged 50 or more at the time of injury. Until 2018, 5,841 patients were enrolled in this study. Follow-up surveys were conducted annually to determine occurrence of second osteoporotic fracture, and 4,803 participants completed at least one follow-up survey. Discussion KHFR is a unique resource of individual level on osteoporotic hip fracture with radiological, medical, and laboratory information including DXA (dual energy x-ray absorptiometry), bone turnover marker, body composition, and hand grip strength for future analyses for FLS model. Modifiable factors for mortality after hip surgery is planned to be identified with nutritional assessment and multi-disciplinary interventions from hospitalization to follow-ups. The proportions of femoral neck, intertrochanteric, and subtrochanteric fractures were 517 (42.0%), 730 (53.6%), and 60 (4.4%), respectively, from 2014 to 2016, which was similar in other studies. Radiologic definition of atypical subtrochanteric fracture was adopted and 17 (1.2%) fractures among 1,361 proximal femoral fractures were identified. Internal fixation showed higher reoperation rate compared to arthroplasty in unstable intertrochanteric fractures (6.1% vs. 2.4%, p = 0.046) with no significant difference in mortality. The KHFR plans to identify outcomes and risk factors associated with second fracture by conducting a 10-year cohort study, with a follow-up every year, using 5,841 baseline participants. Trial registration Present study was registered on Internet-based Clinical Research and Trial management system (iCReaT) as multicenter prospective observational cohort study (Project number: C160022, Date of registration: 22th, Apr, 2016).

Abstract The worldwide persistence of infectious diseases is a significant public health issue. Consequently, studying immunomodulatory ingredients present in natural products, such as ginseng, is important for developing new treatment options. Here, we extracted three different types of polysaccharides from white (P-WG), red (P-RG), and heat-processed (P-HPG) ginseng and analyzed their chemical properties and immunostimulatory activity against RAW 264.7 murine macrophages. Carbohydrates were the main components of all three polysaccharide types, while uronic acid and protein levels were relatively low. Chemical analysis indicated that the content of carbohydrates (total sugar) increased with processing temperature, while that of uronic acid decreased. Treatment with P-WG, P-RG or P-HPG stimulated nitric oxide (NO) production and increased tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 levels in RAW 264.7 macrophages, with P-WG showing the highest activity among the three polysaccharides. The expression of inducible NO synthase, which affects NO secretion, was highest in the macrophages treated with P-WG. Analysis of intracellular signaling pathways showed that mitogen-activated protein kinases (ERK, JNK, and p38) and NF-kB p65 were strongly phosphorylated by P-WG in macrophages but were only moderately phosphorylated by P-RG and P-HPG. Collectively, these results suggest that the polysaccharides isolated from ginseng undergo different changes in response to heat processing and display different chemical compositions and immune-enhancing activities.

Abstract Background Muscle atrophy, leading to muscular dysfunction and weakness, is an adverse outcome of sustained period of glucocorticoids usage. However, the molecular mechanism underlying this detrimental condition is currently unclear. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in skeletal muscle and has been implicated in the pathogenesis of several diseases. The current study was designed to investigated and delineate the role of PDK4 in the context of muscle atrophy, which could be identified as a potential therapeutic avenue to protect against dexamethasone‐induced muscle wasting. Methods The dexamethasone‐induced muscle atrophy in C2C12 myotubes was evaluated at the molecular level by expression of key genes and proteins involved in myogenesis, using immunoblotting and qPCR analyses. Muscle dysfunction was studied in vivo in wild‐type and PDK4 knockout mice treated with dexamethasone (25 mg/kg body weight, i.p., 10 days). Body weight, grip strength, muscle weight and muscle histology were assessed. The expression of myogenesis markers were analysed using qPCR, immunoblotting and immunoprecipitation. The study was extended to in vitro human skeletal muscle atrophy analysis. Results Knockdown of PDK4 was found to prevent glucocorticoid‐induced muscle atrophy and dysfunction in C2C12 myotubes, which was indicated by induction of myogenin (0.3271 ± 0.102 vs 2.163 ± 0.192, ****P

Abstract Cementless bipolar hemiarthroplasty (BHA) recently gained popularity as a treatment for femur neck fracture (FNF), but there have been few studies comparing this with multiple screw fixation (MSF) in the elderly population. The purpose of this study is to compare (1) surgery-related parameters, (2) reoperation rate as a local complication, (3) in-hospital systemic complication rate, and (4) mortality rate at 1 year after MSF and cementless BHA in patients with FNF using nationwide data. Six-hundred sixty-six hips (aged ≥ 50 years) extracted from nationwide Hip Fracture Registry were included in this study (133 MSF and 533 cementless BHA). One hundred fifty-six hips were divided into nondisplaced FNF (Group A) and 510 into displaced FNF (Group B). We evaluated (1) surgery-related parameters (anesthesia type, time to surgery, operation time, estimated blood loss and volume of postoperative transfusion), (2) the rate of and reasons for reoperation, (3) the rate and type of in-hospital systemic complications and (4) one-year mortality rate after surgery. In Group A, MSF showed shorter operation time (p = 0.004) and lower incidence of in-hospital systemic complications (p = 0.003). In Group B, cementless BHA demonstrated lower reoperation rate than MSF (p

Background and objectivePolyWare™ software (PW) has been exclusively used in the majority of polyethylene wear studies of total hip arthroplasty (THA). PW measurements can be significantly inaccurate and unrepeatable, depending on imaging conditions or subjective manipulation choices. In this regard, this study aims to shed light on the conditions needed to achieve the best accuracy and reliability of PW measurements.MethodsThe experiment looked at how PW fluctuated based on several measurement conditions. x-ray images of in-vitro THA prostheses were acquired under a clinical x-ray scanning condition. A linear wear rate of 6.67 mm was simulated in combination with an acetabular lateral inclination of 36.6° and anteversion of 9.0°.ResultsAmong all the imported x-ray images, those with a resolution of 1,076 × 1,076 exhibited the best standard deviation in wear measurements as small as 0.01 mm and the lowest frequencies of blurriness. The edge detection area specified as non-square and off the femoral head center exhibited the most blurriness. The x-ray image that scans a femoral head eccentrically placed by 15 cm superior to the x-ray beam center led to a maximum acetabular anteversion measurement error of 5.3°.ConclusionBecause PW has been the only polyethylene wear measurement tool used, identifying its sources of error and devising a countermeasure are of the utmost importance. The results call for PW users to observe the following measurement protocols: (1) the original x-ray image must be a 1,076 × 1,076 square; (2) the edge detection area must be specified as a square with edge lengths of 5 times the diameter of the femoral head, centered at the femoral head center; and (3) the femoral head center or acetabular center must be positioned as close to the center line of the x-ray beam as possible when scanning.

Abstract Background This study aimed to explore older Korean women’s discharge transition experiences after hip fracture surgery. Methods This was a descriptive qualitative study. Face-to-face interviews following hip fracture surgery were conducted on 12 women aged 65–87 years. Data were collected 1 to 2 days before discharge and again 4 weeks after discharge following hip fracture surgery, and were analyzed using qualitative content analysis. Results Four main themes were identified: (1) challenge of discharge transition: unprepared discharge, transfer into other care settings, and eagerness for recovery; (2) physical and psychological distress against recovery: frail physical state and psychological difficulties; (3) dependent compliance: absolute trust in healthcare providers, indispensable support from the family, and passive participation in care; and (4) walking for things they took for granted: hope of walking and poor walking ability. Conclusions After their hip fracture surgeries, older women hoped to be able to walk and perform simple daily chores they previously took for granted. Considering the physical and psychological frailty of older women undergoing hip surgery, systematic nursing interventions including collaboration and coordination with other healthcare professionals and settings are necessary to ensure the quality of continuous care during their post-surgery discharge transition. Encouraging partial weight bearing and initiating intervention to reduce fear of falling at the earliest possible time are essential to attain a stable discharge transition. Additionally, older women should be invited to participate in their care, and family involvement should be encouraged during the discharge transition period in South Korea.

Background Reconstruction intramedullary nail spanning the whole length of the femur has been the gold standard treatment for complete atypical diaphyseal fractures of the femur (ADF). However, in cases of incomplete ADF combined with severe bowing, this approach might have complications and lead to iatrogenic complete fracture. We report two cases of incomplete ADF with severe bowing using a precontoured plate (PCP) after rapid prototyping (RP) of the deformed femurs with three‐dimensional printing (3DP) technology. Case presentation Two patients presented with gradually worsening thigh pain, especially during walking. The patients had been using bisphosphonates for 4 and 10 years, respectively. Radiography showed an incomplete fracture in the lateral cortex of the right femur shaft. The lateral bowing angles measured in the affected femurs were 15° and 14°, and the anterior bowing angles were 20° and 16°, respectively. In bone scans, both patients showed hot uptake in the right mid‐shaft of the femur. Preoperatively, the affected femur of the patient was reconstructed by 3DP RP using CT, and the plate was bent to the shape of the bone model. The ADF was fixed with a PCP using the minimally invasive plate osteosynthesis technique. Both patients were encouraged to start full weight‐bearing and return to their preinjury activity level in daily life immediately after surgery. At 2 years postoperatively, radiography showed healing of the fracture site without recurrence of thigh pain and implant‐related problems. Conclusion Although intramedullary nailing is the standard surgical treatment for complete ADF, PCP using 3DP RP could be an effective treatment option for incomplete ADF with severely curved femur.

Purpose: The aim of this study is to conduct clinical and radiographic evaluations of the use of percutaneous bridge plating for distal fibular fractures combined with distal tibia type III open fractures. Methods: Thirty-four patients with acute distal third fibular shaft fractures (4F2A(c) and 4F2B(c) according to the AO/OTA classification) combined with distal tibia type III open fractures were enrolled. Concurrent fibular fractures were fixed with the percutaneous bridge plating simultaneously, while distal tibia open fractures were temporally stabilized with a spanning external fixator. Clinical and radiographic outcomes were evaluated using the Lower Extremity Functional Scale (LEFS), the proportional length difference of the fibula, the talocrural angle, the union rate of the fibula and tibia, the operation time, and complications at the final follow-up. Results: All fibular fractures healed with an average bone healing time of 20.7 ± 6.3 weeks (range, 16–35). The mean proportional length difference was 0.492 ± 0.732% compared with that in the uninjured fibula. The functional assessment result according to the LEFS was 74.0 ± 3.70 points (range, 57–80). No cases of fibula fracture infection developed throughout the follow-up period in any of the patients. Iatrogenic postoperative superficial peroneal nerve injury was not found in any of the patients. Conclusion: With the perspective of minimizing soft tissue problems due to high-energy trauma, the application of percutaneous bridge plating for the treatment of distal fibular fractures can be an alternative to conventional treatment methods.

Abstract Background The blood–brain barrier (BBB) maintains homeostasis of the brain environment by tightly regulating the entry of substances from systemic circulation. A breach in the BBB results in increased permeability to potentially toxic substances and is an important contributor to amplification of ischemic brain damage. The precise molecular pathways that result in impairment of BBB integrity remain to be elucidated. Autophagy is a degradation pathway that clears damaged or unnecessary proteins from cells. However, excessive autophagy can lead to cellular dysfunction and death under pathological conditions. Methods In this study, we investigated whether autophagy is involved in BBB disruption in ischemia, using in vitro cells and in vivo rat models. We used brain endothelial bEnd.3 cells and oxygen glucose deprivation (OGD) to simulate ischemia in culture, along with a rat ischemic stroke model to evaluate the role of autophagy in BBB disruption during cerebral ischemia. Results OGD 18 h induced cellular dysfunction, and increased permeability with degradation of occludin and activation of autophagy pathways in brain endothelial cells. Immunostaining revealed that occludin degradation is co-localized with ischemic autophagosomes. OGD-induced occludin degradation and permeability changes were significantly decreased by inhibition of autophagy using 3-methyladenine (3-MA). Enhanced autophagic activity and loss of occludin were also observed in brain capillaries isolated from rats with middle cerebral artery occlusion (MCAO). Intravenous administration of 3-MA inhibited these molecular changes in brain capillaries, and recovered the increased permeability as determined using Evans blue. Conclusions Our findings provide evidence that autophagy plays an important role in ischemia-induced occludin degradation and loss of BBB integrity.

Abstract Background The deformity of the proximal femur and acetabular in patients with developmental dysplasia of the hip (DDH) renders an intraoperative decision for ideal component placement challenging. We hypothesized that the altered morphology of calcar femorale (CF) in DDH patients changed the fixation mechanism of the cementless metaphyseal-filling stem and aimed to predict stem anteversion using proximal femoral anatomical parameters from preoperative CT. Methods Preoperative and postoperative CT scans of 34 DDHs with a metaphyseal-filling stem in THA were retrospectively analyzed. Proximal femoral anatomical parameters, including the femoral anteversion (FA) and the CF angles at the low femoral neck (LFN) and the center of the lesser trochanter (CLT) levels (FA-LFN, FA-CLT, CF-LFN, and CF-CLT) were measured. The dysplastic hips were divided into the CF group (n = 21) and the non-CF group (n = 13) according to the presence of the CF-LFN. The association between the anatomical parameters and the postoperative stem anteversion was statistically analyzed, and the predicted stem anteversion was compared with postoperative stem anteversion. Results In the CF group, the combination of the CF-LFN and FA-CLT exhibited a strong positive correlation (R = 0.870, p < 0.001) with the postoperative stem anteversion. In the non-CF group, only the FA-LFN had a strong positive correlation (R = 0.864, p < 0.001). Average prediction errors were 5.9° and 6.4° in the CF and non-CF groups. Conclusions The presence of CF-LFN is related to the press-fit mechanism of the metaphyseal-filling stem, and the preoperative measurements from CT images can be employed as a tool to predict postoperative stem anteversion in DDH patients.

In pediatric patients, a laryngeal mask airway (LMA) is usually used during minor surgeries that require general anesthesia. No esophageal injury has been reported after insertion of an LMA. We report a case of an esophageal injury with intramural dissection after an i-gel® (size, 1.5; Intersurgical Ltd.) insertion in a pediatric patient. A 2-month-old male infant was hospitalized for left inguinal herniorrhaphy. After induction of anesthesia, a trained resident tried to insert an i-gel® . However, it was only successful after three attempts. Dysphagia was sustained until postoperative day 10, and the pediatrician observed duplication of the esophagus on gastroendoscopy. However, a whitish mucosal lesion, which looked like a scar, was observed, and previous lesions suggestive of esophageal duplication were almost healed on postdischarge day 11. His condition was diagnosed as dysphagia and esophagitis due to an esophageal laceration, not esophageal duplication. He was scheduled for symptomatic treatment with a proton pump inhibitor. In conclusion, although an esophageal injury or perforation in pediatric patients is rare, an LMA insertion or a procedure such as aspiration or nasogastric tube insertion should be performed gently to avoid a possible injury to the esophagus in pediatric patients.

Introduction: Older patients with hip fractures require a long time to rehabilitate and recover after surgery. Although effective discharge instructions for long-term recovery are important, the discharge instructions of most acute-care hospitals are often presented as a brochure, which is difficult for older adults to follow. The purpose of this study was to develop rehabilitation instructions in the form of a mobile application for the physical recovery of older adults after hip fracture surgery. Materials and Methods: A mobile application for rehabilitation instructions after hip fracture surgery was developed in ADDIE order of analysis, design, development, implementation, and evaluation. The contents of the mobile application composed of rehabilitative exercises, activities of daily living, pain and nutrition management, fall prevention, and hospital visits. Nine experts evaluated the application and SPSS version 23.0 program was used for data analysis. Results: In the mobile application evaluation by the experts, the average score of the contents was 2.22 out of 3 points. The average score of understanding was the highest at 2.42, while accuracy was the lowest at 2.00 in the contents. The average score of the interface design was 2.32 out of 3 points. The average score of consistency was the highest at 2.42, while design suitability was the lowest at 2.25 in the interface design. The experts perceived the mobile application as simple and easy to understand while also suggesting some improvements. Conclusion: The average scores were highest for understanding of contents and consistency of the interface design and lowest for accuracy of contents and design suitability of the interface design. The mobile application was easy to understand and had consistency in design.

A highly efficient metal-free oxidative direct C(sp3)–H functionalization of N-acyl/sulfonyl 1,2,3,4-tetrahydroisoquinolines (THIQs) with a wide range of electron-rich nucleophiles was accomplished under mild conditions through oxidation with DDQ and subsequent trapping of the resulting reactive and stable N-acyl/sulfonyl iminium ions. The synthetic utility of this method was illustrated by a concise and efficient total synthesis of (±)-benzo[a]quinolizidine (10) in 3 steps from the known N-Cbz 1,2,3,4-THIQ 4b.

Panax ginseng C.A. Meyer (ginseng) has shown immune-enhancing activity in many studies. The purpose of the present study was to analyze the chemical properties of a polysaccharide fraction (SGP) purified from heat- processed ginseng and to evaluate its immune-enhancing activity using RAW264.7 macrophages. The results showed that SGP increased inducible nitric oxide synthase expression and nitric oxide production in RAW264.7 macrophages. In addition, SGP increased mRNA expression and secretion of interleukin 6 and tumor necrosis factor alpha. Immunoblotting results showed that SGP increased the phosphorylation of mitogen-activated protein kinases (MAPKs) and NF-κB subunit p65 at 500 μg/mL and 1000 μg/mL. Taken together, SGP can activate macrophages through the MAPK and NF-κB signaling pathways, and it may help maintain homeostasis during viral and bacterial infections.

Dendropanax morbifera leaves (DML) have long been used as traditional medicine to treat diverse symptoms in Korea. Ethyl acetate-soluble extracts of DML (DMLE) rescued HT22 mouse hippocampal neuronal cells from glutamate (Glu)-induced oxidative cell death; however, the protective compounds and mechanisms remain unknown. Here, we aimed to identify the neuroprotective ingredients and mechanisms of DMLE in the Glu-HT22 cell model. Five antioxidant compounds were isolated from DMLE and characterized as chlorogenic acid, hyperoside, isoquercitrin, quercetin, and rutin by spectroscopic methods. Isoquercitrin and quercetin significantly inhibited Glu-induced oxidative cell death by restoring intracellular reactive oxygen species (ROS) levels and mitochondrial superoxide generation, Ca2+ dysregulation, mitochondrial dysfunction, and nuclear translocation of apoptosis-inducing factor. These two compounds significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the presence or absence of Glu treatment. Combinatorial treatment of the five compounds based on the equivalent concentrations in DMLE showed that significant protection was found only in the cells cotreated with isoquercitrin and quercetin, both of whom showed prominent synergism, as assessed by drug–drug interaction analysis. These findings suggest that isoquercitrin and quercetin are the active principles representing the protective effects of DMLE, and these effects were mediated by the Nrf2/HO-1 pathway.

Background: Nephrotoxicity is the major side effect in cisplatin chemotherapy. Previously, we reported that the ginsenosides Rk3 and Rh4 reduced cisplatin toxicity on porcine renal proximal epithelial tubular cells (LLC-PK1). Here, we aimed to evaluate the protective effect of ginsenosides Rk3 and Rh4 on kidney function and elucidate their antioxidant effect using in vitro and in vivo models of cisplatin-induced acute renal failure. Methods: An enriched mixture of ginsenosides Rk3 and Rh4 (KG-KH; 49.3% and 43.1%, respectively) was purified from sun ginseng (heat processed Panax ginseng). Cytotoxicity was induced by treatment of 20μM cisplatin to LLC-PK1 cells and rat model of acute renal failure was generated by single intraperitoneal injection of 5 mg/kg cisplatin. Protective effects were assessed by determining cell viability, reactive oxygen species generation, blood urea nitrogen, serum creatinine, antioxidant enzyme activity, and histopathological examination. Results: The in vitro assay demonstrated that KG-KH (50 μg/mL) significantly increased cell viability (4.6-fold), superoxide dismutase activity (2.8-fold), and glutathione reductase activity (1.5-fold), but reduced reactive oxygen species generation (56%) compared to cisplatin control cells. KG-KH (6 mg/kg, per os) also significantly inhibited renal edema (87% kidney index) and dysfunction (71.4% blood urea nitrogen, 67.4% creatinine) compared to cisplatin control rats. Of note, KG-KH significantly recovered the kidney levels of catalase (1.2-fold) and superoxide dismutase (1.5-fold). Conclusion: Considering the oxidative injury as an early trigger of cisplatin nephrotoxicity, our findings suggest that ginsenosides Rk3 and Rh4 protect the kidney from cisplatin-induced oxidative injury and help to recover renal function by restoring intrinsic antioxidant defenses.

Background: Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods: LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results: The reduction in LLC-PK1 cell viability by 60μM FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with 60μM FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by 60μM FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion: Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

Background: It is important to investigate the level of physical function impairment before fracture to predict mortality after hip fracture. This study aimed to examine the predictive factors associated with mortality depending on prefracture physical function impairment among Korean elderly patients. Methods: We included 1841 patients aged 65 years and older with hip fractures using osteoporosis-related hip fracture network data from 15 university hospitals in South Korea. The collected data included sociodemographic, nutritional, disease-related, and fracture- and surgery-related factors. For the degree of prefracture physical function impairment, ambulatory ability was classified into community, household, and nonfunctional ambulators. Binominal logistic regression was used to identify the predictive factors for mortality. Results: Analysis showed that mortality rate at the first follow-up after hip fracture was 4.9%, and most patients (77.7%) were community ambulators before fracture. Sociodemographic (older age, male sex), nutritional (low body mass index, low albumin level before surgery), and fracture- and surgery-related (nonsurgical management, complications after surgery) factors significantly predicted mortality, depending on the prefracture ambulatory status. Conclusions: This study emphasizes that nutritional assessment and management as interdisciplinary interventions from hospitalization to follow-ups should be performed to lower malnutrition and mortality risk. Therapeutic management for comorbidities negatively affecting surgery outcomes should be prioritized to reduce postoperative complications and mortality. Surgical treatment should be encouraged if it aligns with the therapeutic goals, even in poor health status.

Amorphous solid dispersions (ASDs) improve the oral delivery of poorly water-soluble drugs. ASDs of olanzapine (OLZ), which have a high melting point and low solubility, are performed using a complicated process. Three-dimensional (3D) printing based on hot-melt pneumatic extrusion (HMPE) is a simplified method for producing ASDs. Unlike general 3D printing, printlet extrusion is possible without the preparation of drug-loaded filaments. By heating powder blends, direct fused deposition modeling (FDM) printing through a nozzle is possible, and this step produces ASDs of drugs. In this study, we developed orodispersible films (ODFs) loaded with OLZ as a poorly water-soluble drug. Various ratios of film-forming polymers and plasticizers were investigated to enhance the printability and optimize the printing temperature. Scanning electron microscopy (SEM) showed the surface morphology of the film for the optimization of the polymer carrier ratios. Differential scanning calorimetry (DSC) was used to evaluate thermal properties. Powder X-ray diffraction (PXRD) confirmed the physical form of the drug during printing. The 3D printed ODF formulations successfully loaded ASDs of OLZ using HMPE. Our ODFs showed fast disintegration patterns within 22 s, and rapidly dissolved and reached up to 88% dissolution within 5 min in the dissolution test. ODFs fabricated using HMPE in a single process of 3D printing increased the dissolution rates of the poorly water-soluble drug, which could be a suitable formulation for fast drug absorption. Moreover, this new technology showed prompt fabrication feasibility of various formulations and ASD formation of poorly water-soluble drugs as a single process. The immediate dissolution within a few minutes of ODFs with OLZ, an atypical antipsychotic, is preferred for drug compliance and administration convenience.

l-carnosine is an attractive therapeutic agent for acute ischemic stroke based on its robust preclinical cerebroprotective properties and wide therapeutic time window. However, large doses are needed for efficacy because carnosine is rapidly degraded in serum by carnosinases. The need for large doses could be particularly problematic when translating to human studies, as humans have much higher levels of serum carnosinases. We hypothesized that d-carnosine, which is not a substrate for carnosinases, may have a better pharmacological profile and may be more efficacious at lower doses than l-carnosine. To test our hypothesis, we explored the comparative pharmacokinetics and neuroprotective properties of d- and L-carnosine in acute ischaemic stroke in mice. We initially investigated the pharmacokinetics of d- and L-carnosine in serum and brain after intravenous (IV) injection in mice. We then investigated the comparative efficacy of d- and l-carnosine in a mouse model of transient focal cerebral ischemia followed by in vitro testing against excitotoxicity and free radical generation using primary neuronal cultures. The pharmacokinetics of d- and l-carnosine were similar in serum and brain after IV injection in mice. Both d- and l-carnosine exhibited similar efficacy against mouse focal cerebral ischemia. In vitro studies in neurons showed protection against excitotoxicity and the accumulation of free radicals. d- and l-carnosine exhibit similar pharmacokinetics and have similar efficacy against experimental stroke in mice. Since humans have far higher levels of carnosinases, d-carnosine may have more favorable pharmacokinetics in future human studies.

The complete genome of Vaccinium oldhamii plastid was sequenced and analyzed in this study. The V. oldhamii plastid a circular genome of 173,245 bp with 33 genes, including 88 protein, 37 tRNA, and eight rRNA genes. Phylogenetic analysis showed that species of Vaccinium were the first branching taxon In Ericaceae.

Multinucleated osteoclasts differentiate from hematopoietic progenitors of the monocyte/macrophage lineage. Because of its pivotal role in bone resorption, regulation of osteoclast differentiation is a potential therapeutic approach to the treatment of erosive bone disease. In this study, we have found that fucoidan, a sulfated polysaccharide extracted from brown seaweed, inhibited osteoclast differentiation. In particular, addition of fucoidan into the early stage osteoclast cultures significantly inhibited receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast formation, thus suggesting that fucoidan affects osteoclast progenitors. Furthermore, fucoidan significantly inhibited the activation of RANKL-dependent mitogen-activated protein kinases (MAPKs) such as JNK, ERK, and p38, and also c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis. In addition, the activation of NF-κB, which is an upstream transcription factor modulating NFATc1 expression, was alleviated in the fucoidan-treated cells. These results collectively suggest that fucoidan inhibits osteoclastogenesis from bone marrow macrophages by inhibiting RANKL-induced p38, JNK, ERK and NF-κB activation, and by downregulating the expression of genes that partake in both osteoclast differentiation and resorption.

The complete chloroplast (cp) genome sequence of Actinidia rufa was determined by next-generation sequencing in this study. The whole cp genome was 156,543 bp in length, containing a large single-copy (LSC) of 88,435 bp and a small single-copy (SSC) region of 20,307 bp, which was separated by a pair of 23,900 bp inverted repeat (IR) regions. The genome contained 131 genes, including 84 protein-coding genes, 39 tRNA genes, 8 ribosomal RNA genes. Two events were found in the Actinidiaceae chloroplast genome. One was the deletion of the clpP gene and the other was the trnfM-CAU gene in the same direction in LSC region. The phylogenetic position of A. rufa was closely clustered with A. chinensis, A. deliciosa as sister species.

The complete chloroplast (cp) genome sequence of Larix kaempferi and L. olgensis var. koreana were determined by Ion torrent Platform sequencing in this study. The L. kaempferi cp genome was 122,158bp consists of two inverted repeat (IR) regions of 436bp each, a large single-copy (LSC) region of 65,394bp, and a small single-copy (SSC) region of 55,892bp. The chloroplast genome sequence of L. olgensis var. koreana was 122,573bp in length, consisting of two IRs (436bp), one LSC (65,597bp), and one SSC (56,104bp), and is longer than that of L. kaempferi. The genome contained 110 genes, including 71 protein-coding genes, 35 tRNA genes, and 4 ribosomal RNA genes. The 13 genes contain introns, including 12 genes with a single intron each and ycf3 gene with two introns. And, the rps12 gene is a trans-spliced gene. The phylogenetic analysis revealed that all sampled species in Pinaceae formed a monophyletic clade with high bootstrap value. The genus Larix is closely related to Pseudotsuga.

The skin is an important physiological barrier against external stimuli, such as ultraviolet radiation (UV), xenobiotics, and bacteria. Dermal inflammatory reactions are associated with various skin disorders, including chemical-induced irritation and atopic dermatitis. Modulation of skin inflammatory response is a therapeutic strategy for skin diseases. Here, we synthesized chrysin-derivatives and identified the most potent derivative of Compound 6 (CPD 6). We evaluated its anti-inflammatory effects in vitro cells of macrophages and keratinocytes, and in vivo dermatitis mouse models. In murine macrophages stimulated by lipopolysaccharide (LPS), CPD 6 significantly attenuated the release of inflammatory mediators such as nitric oxide (NO) (IC50 for NO inhibition: 3.613 μM) and other cytokines. In cultured human keratinocytes, CPD 6 significantly attenuated the release of inflammatory cytokines induced by the combination of IFN-γ and TNF-α, UV irradiation, or chemical irritant stimulation. CPD 6 inhibited NFκB and JAK2/STAT1 signaling pathways, and activated Nrf2/HO-1 signaling. In vivo relevancy of anti-inflammatory effects of CPD 6 was observed in acute and chronic skin inflammation models in mice. CPD 6 showed significant anti-inflammatory properties both in vitro cells and in vivo dermatitis animal models, mediated by the inhibition of the NFκB and JAK2-STAT1 pathways and activation of Nrf2/HO-1 signaling. We propose that the novel chrysin-derivative CPD 6 may be a potential therapeutic agent for skin inflammation.

Fraxinus chiisanensis is endemic to Korea and restricted to local habitats with an extremely limited population size. The chloroplast genomic information can be used to formulate a comprehensive conservation strategy. In this study, the complete chloroplast (cp) genome sequence of F. chiisanensis was determined using next-generation sequencing. The entire cp genome was determined to be 155,571 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 86,412 of 17,767 bp, respectively, which were separated by a pair of 25,696 bp inverted repeat (IR) regions. The genome contained 132 genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Among the 132 genes, seven coding genes, seven tRNA genes, and four rRNA genes occur in the two IR regions. The phylogenetic position of F. chiisanensis in Oleaceae was closely clustered with Olea, Chionanthus retusus, and Hesperelaea palmeri as sister species.

BackgroundSedation in spinal anesthesia can reduce patient's anxiety and discomfort. Dexmedetomidine has a sedative, hypnotic, analgesic, and minimal respiratory depression effect. However, use of the dexmedetomidine is associated with prolonged recovery. This study was designed to investigate the optimal dose of intravenous dexmedetomidine for proper sedation with minimal recovery time in spinal anesthesia.MethodsOne hundred twenty eight patients, aged 20-70 years (58.8 ± 0.7), were recruited. After performing the spinal anesthesia with hyperbaric bupivacaine (13 mg), a loading dose of dexmedetomidine (1 µg/kg) was administered for 10 min, followed by the maintenance infusion of the following: Group A (n = 33; normal saline), Group B (n = 35; dexmedetomidine 0.2 µg/kg/hr), and Group C (n = 39; dexmedetomidine 0.4 µg/kg/hr). Heart rate, blood pressure, and the bispectral index score (BIS) were recorded during the operation. In the recovery room, modified aldrete score (MAS) was measured.ResultsThere were no significant differences in mean blood pressure and heart rate among the three groups. BIS was not significantly different among the three groups from baseline to 60 min after the infusion of dexmedetomidine. BIS were significantly increased in Group A after 70 and 80 min, and Group A and B after 90, 100, 110 min of dexmedetomidine infusion (P < 0.05). MAS was higher in Group A as compared to Group B and C, within 30 min after admission in the recovery room (P < 0.05).ConclusionsThe loading dose (1 µg/kg/10 min) of dexmedetomidine was sufficient for surgery of less than 60 min. Dexmedetomidine infusion followed by maintenance dose (0.2 µg/kg/hr) was sufficient for surgery within 90 min.

BackgroundRecently, the addition of dexmedetomidine to sedation regimens after cardiac surgery had been reported and there is a possibility that dexmedetomidine can cause vasoconstriction. Vasopressin has been used as a prophylactic treatment for refractory vasodilatory shock during coronary artery bypass graft (CABG). Also, vasopressin may play an important role in initiating spasms at the graft artery. Here we evaluate the direct effect of dexmedetomidine on isolated human gastroepiploic arteries and the synergistic effect of dexmedetomidine and vasopressin.MethodsDiscarded gastroepiploic arteries from elective subtotal gastrectomy (n = 10) were used in this study. We measured the level of contraction in isolated human gastroepiploic arteries induced by increasing concentrations of dexmedetomidine (10-10 to 10-6 M) with or without vasopressin (10-10, 10-9 M). Arterial contractions caused by increasing concentrations of vasopressin (10-10 to 10-7.5 M) with or without dexmedetomidine (10-9, 10-7 M) were also measured in the tissue samples.ResultsSupraclinical concentrations of dexmedetomidine elicited contractions at concentrations of 10-7 M and 10-6 M (P < 0.05 versus resting tension). The same concentrations of dexmedetomidine (10-7, 10-6 M) significantly enhanced vasopressin-induced contractions (P < 0.05 versus vasopressin-induced contraction). Vasopressin produced concentration-dependent contractions and vasopressin (10-10, 10-9.5, 10-9 M) also increased the intensity of dexmedetomidine (10-7 M) induced contractions.ConclusionsThere was a synergistic effect between supraclinical doses of dexmedetomidine and vasopressin on the degree of contraction in isolated human gastroepiploic arteries. However, a sedative dose of dexmedetomidine (clinical dose: 0.2-0.7 µg/kg/hr, plasma concentration: 0.36-1.25 ng/ml) did not enhance vasopressin induced-contraction in isolated human gastroepiploic arteries.

Transesophageal echocardiography (TEE) has an important role during congenital heart surgery. TEE in small infants is associated with complications, including an inability to pass the TEE probe, esophageal trauma, airway compression, aortic compression, and interference with ventilation. Recently, a monoplane intravascular ultrasound catheter (IVUC) has been developed for intracardiac echocardiography. The efficacy of IVUC for transesophageal use has been shown in numerous animal studies and several human studies, but there have been few reports involving small infants using an IVUC probe. We examined 15 pediatric patients undergoing congenital cardiac surgery using an 8-Fr AcuNav IVUC probe. We checked the cardiac anatomy, cardiac function pre-operatively and de-aeration before weaning from CPB; the surgical repairs were evaluated post-operatively. Although the IVUC probe has limitations associated with the monoplane, we found the IVUC probe to be useful in small infants and safer than the TEE.