Search

Background: Altered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aβ) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aβ and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aβ and tau deposition. Methods: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET. Results: No associations were found between either thyroid hormones or TSH and Aβ and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aβ on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aβ deposition was not significant, whereas the interaction between fT3 and Aβ deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aβ and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aβ on tau deposition. Conclusion: Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aβ and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aβ-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) infection constitutes a substantial disease burden in the general population. However, the risk of death for RSV infection has been rarely evaluated with confounders or comorbidities adjusted. We aimed to evaluate whether RSV infection is associated with higher mortality than seasonal influenza after adjusting for confounders and comorbidities and the effect of oseltamivir on the mortality in patients with influenza infection.Methods: A retrospective cohort study was conducted on adult (≥18 years) patients admitted to the emergency department and ward of a university teaching hospital for suspected viral infection during 2013-2015 (N = 3743). RSV infection was diagnosed by multiplex PCR (N = 87). Adults hospitalized for seasonal influenza during the study period were enrolled as a comparison group (n = 312). The main outcome was 20-day all-cause mortality.We used Cox proportional hazard regression analyses to calculate the relative risk of death.Results: Adult patients were less likely to be diagnosed with RSV than with influenza (2.3 vs 8.3%, respectively), were older and more likely to be diagnosed with pneumonia, chronic obstructive pulmonary disease, hypoxemia, and bacterial co-infection. In patients with RSV infection, the 20-day all-cause mortality was higher than that for influenza, (18.4 vs 6.7%, respectively). RSV infection showed significantly higher risk of death compared to the seasonal influenza group, with hazard ratio, 2.32 (95% CI, 1.17-4.58). Oseltamivir had no significant effect on mortality in patients with influenza.Conclusions: RSV infection was significantly associated with a higher risk of death than seasonal influenza, adjusted for potential confounders and comorbidities. [ABSTRACT FROM AUTHOR]

Background: The impact of meat consumption on high blood pressure (HBP) and obesity in children and adolescents is a subject of debate. The aim of this study was thus to evaluate the association between meat consumption and both HBP and obesity in this group.Methods: We performed a cross-sectional analysis using nationally representative samples of children and adolescents aged 9, 12, and 15 years old (n = 136,739) who were included in the Korea School Health Examination Survey (KSHES) for the 2011-2015 period. Multiple linear and logistic regression analysis was used to determine the factors influencing systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI, kg/m2) levels, and to test the strength of these relationships.Results: Adjusted for covariates, 6.3% of those subjects who consumed >5 servings of meat (including beef, pork, and chicken) per week were obese, compared with 9.1% of the subjects who consumed <1 serving of meat/wk (obesity adjusted odds ratio [OR]: 1.44; 95% confidence interval [CI]: 1.21-1.70; P ≤0.001). Those who consumed <1 serving of meat/wk had an HBP prevalence of 8.2%, compared with 7.2% for subjects who consumed >5 servings of meat/wk (systolic HBP adjusted OR: 1.30; 95% CI: 1.05-1.62; P ≤0.01, diastolic HBP adjusted OR: 1.25; 95% CI: 1.02-1.54; P <0.05). Obese subjects were estimated to have a higher SBP (β = 7.497, P < 0.001) and DBP (β = 4.123, P <0.001) than subjects who had no excess weight. Compared to subjects who consumed >5 servings of meat/wk, those who consumed <3 servings of meat/wk had a higher SBP (β = 0.574, P <0.001) and DBP (β = 0.376, P = 0.003) after adjusting for BMI. The intake of milk, fruit, and vegetables was not associated with either SBP or DBP (P >0.05). In contrast, BMI was significantly associated with milk, fruits, and vegetables (P <0.01).Conclusions: Among children and adolescents, a higher level of meat consumption was associated with lower SBP, DBP, and BMI, and greater height, suggesting that consuming an appropriate amount of meat is important for healthy growth at a young age. [ABSTRACT FROM AUTHOR]

Robot-assisted gait training (RAGT) after spinal cord injury (SCI) induces several different neurophysiological mechanisms to restore walking ability, including the activation of central pattern generators, task-specific stepping practice and massed exercise. However, there is no clear evidence for the optimal timing and efficacy of RAGT in people with SCI. The aim of our study was to assess the effects of RAGT on improvement in walking-related functional outcomes in patients with incomplete SCI compared with other rehabilitation modalities according to time elapsed since injury. This review included 10 trials involving 502 participants to meta-analysis. The acute RAGT groups showed significantly greater improvements in gait distance, leg strength, and functional level of mobility and independence than the over-ground training (OGT) groups. The pooled mean difference was 45.05 m (95% CI 13.81 to 76.29, P = 0.005, I2 = 0%; two trials, 122 participants), 2.54 (LEMS, 95% CI 0.11 to 4.96, P = 0.04, I2 = 0%; three trials, 211 participants) and 0.5 (WISCI-II and FIM-L, 95% CI 0.02 to 0.98, P = 0.04, I2 = 67%; three trials, 211 participants), respectively. In the chronic RAGT group, significantly greater improvements in speed (pooled mean difference = 0.07 m/s, 95% CI 0.01 to 0.12, P = 0.01, I2 = 0%; three trials, 124 participants) and balance measured by TUG (pooled mean difference = 9.25, 95% CI 2.76 to 15.73, P = 0.005, I2 = 74%; three trials, 120 participants) were observed than in the group with no intervention. Thus, RAGT improves mobility-related outcomes to a greater degree than conventional OGT for patients with incomplete SCI, particularly during the acute stage. RAGT treatment is a promising technique to restore functional walking and improve locomotor ability, which might enable SCI patients to maintain a healthy lifestyle and increase their level of physical activity.Trial Registration: PROSPERO (CRD 42016037366 ). Registered 6 April 2016. [ABSTRACT FROM AUTHOR]

Background: Pemetrexed is widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSCLC). However, factors that can predict the benefits of pemetrexed therapy have not yet been defined.Methods: We compared the clinical and molecule pathological characteristics of good and poor responders among a cohort of 1,848 non-squamous NSCLC patients who had received at least two cycles of pemetrexed therapy between November 2006 and February 2015. Among these cases, 92 good responders who were the top 5 % in terms of progression-free survival (PFS) and 222 poor responders who had progressive disease after only 2 cycles of therapy were selected for the analysis.Results: The median PFS of the good responders was 29.9 months (range; 20.9-90.0) and the median number of cycle was 37 (range; 18-129). Although 53.5 % of patients showed stable disease (SD), this response was sustained (median PFS in SD, 29.6 months). A never-smoking status was related to better survival outcome, whereas EGFR mutation, two or more metastatic sites, and intra-abdominal metastasis were each associated with a poor PFS. ALK translocation showed a tendency for a positive impact on response to pemetrexed, whereas metastatic lesion to liver, adrenal gland or bone showed a tendency for a negative impact despite not reaching our threshold for statistical significance.Conclusions: Predictive factors, such as smoking status, the status of genetic alteration and tumor burden, should be considered when administering pemetrexed therapy for non-squamous NSCLC. [ABSTRACT FROM AUTHOR]

Background: Despite abundant theoretical evidence of higher rates of suicide among lesbian, gay, and bisexual (LGB) youths, little is known about the relationship between suicide and types of sexual intercourse experience in youths. This study examines the association between the type of intercourse experience and suicide risk outcomes (SROs: suicidal ideation, plans for suicide, suicidal attempts) from the Korea Youth Risk Behavior Web-based Survey.Methods: We analyzed cross-sectional data from 146,621 students aged 12-17 years for the years 2012 and 2013. We defined lesbian, gay, or bisexual youth as youths who engaged in a type of sexual intercourse (same-sex or both-sex intercourse). A chi-square test and logistic regression analysis were used to evaluate the association between intercourse experience and SROs.Results: The results showed that the prevalence of suicidal ideation was higher among youths with same-sex intercourse experience (45.9% for females, 33.7% for males) than among youths with opposite-sex intercourse experience (42.2% for females, 23.8% for males) and those with no experience in intercourse (21.0% for females, 12.7% for males). After adjusting for revealed risk factors that were associated with suicide risks, among males, suicide risks based on intercourse experience seemed to increase in the following order: no experience in sexual intercourse, opposite-sex, same-sex, and then both-sexes sexual intercourse experience. Same- and both-sexes intercourse related SROs are strongly linked to violence (being physically assaulted, threatened, or bullied) and sexually transmitted diseases (STDs), including HIV infection. Those having no sexual intercourse experience showed the least probability of suicide risks among youths.Conclusion: The SROs of youths with same-sex or both-sex intercourse experience had strong associations with gender (males), violence, and STDs. Therefore, school educators must continue to advocate for and to implement LGB inclusive policies and programs in order to promote safe and supportive learning environments where all students are protected from health risk behaviors. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. The gene encoding Cu/Zn superoxide dismutase (SOD1) is responsible for 20% of familial ALS cases. Growth hormone (GH) concentrations are low in the cerebrospinal fluid of patients with ALS; however, its association with motoneuronal death is not known. We tested the neuroprotective effects of GH on human SOD-1-expressing cultured motor neurons and SOD1G93A transgenic mice. Results: In cultured motor neurons, cytotoxicity was induced by A23187, GNSO, or homocysteine, and the effects of GH were determined by MTT, bax, PARP cleavage pattern, Hoechst nuclear staining, MAPK, and PI3K assay. In SOD-1 transgenic mice, rotarod motor performance was evaluated. Survival analysis of motoneuronal loss was done using cresyl violet, GFAP, and Bcl-2 staining. GH prevents motorneuronal death caused by GSNO and homocysteine, but not that by A23187. It activates MAPK and PI3K. GH-treated mice showed prolonged survival with improved motor performance and weight loss. GH decreased cresyl violet positive motoneuronal loss with strong Bcl-2 and less GFAP immunoreactivity. Conclusions: Our results demonstrate that GH has a protective effect on mutant SOD-1-expressing motor neurons. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that the combination of non-invasive brain stimulation and motor skill training is an effective new treatment option in neurorehabilitation. We investigated the beneficial effects of the application of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) motor training.Methods: In total, 15 healthy, right-handed volunteers and 15 patients with stroke in the subacute stage participated. Four different conditions (A: active wrist exercise, B: VR wrist exercise, C: VR wrist exercise following anodal tDCS (1 mV, 20 min) on the left (healthy volunteer) or affected (stroke patient) primary motor cortex, and D: anodal tDCS without exercise) were provided in random order on separate days. We compared during and post-exercise corticospinal excitability under different conditions in healthy volunteers (A, B, C, D) and stroke patients (B, C, D) by measuring the changes in amplitudes of motor evoked potentials in the extensor carpi radialis muscle, elicited with single-pulse transcranial magnetic stimulation. For statistical analyses, a linear mixed model for a repeated-measures covariance pattern model with unstructured covariance within groups (healthy or stroke groups) was used.Results: The VR wrist exercise (B) facilitated post-exercise corticospinal excitability more than the active wrist exercise (A) or anodal tDCS without exercise (D) in healthy volunteers. Moreover, the post-exercise corticospinal facilitation after tDCS and VR exercise (C) was greater and was sustained for 20 min after exercise versus the other conditions in healthy volunteers (A, B, D) and in subacute stroke patients (B, D).Conclusions: The combined effect of VR motor training following tDCS was synergistic and short-term corticospinal facilitation was superior to the application of VR training, active motor training, or tDCS without exercise condition. These results support the concept of combining brain stimulation with VR motor training to promote recovery after a stroke. [ABSTRACT FROM AUTHOR]

Purpose: Anterior cruciate ligament (ACL) injury is one of the most common injuries that occur in the knee, and ACL reconstruction (ACLR) is commonly performed for preventing aggravation of degenerative changes and restoring of knee stability in young, athletic patients. This meta-analysis has a purpose of evaluating the clinical and arthrometrical outcomes of ACLR in a group of middle age patients (40 years and older) and comparing with patients under 40 years of age., Methods: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and SCOPUS electronic databases were searched for relevant articles comparing the outcomes of ACLR between younger and older than 40 years of age until December 2016. Data searching, extraction, analysis, and quality assessment were performed based on the Cochrane Collaboration guidelines. Clinical outcomes were evaluated and compared between groups. The results were presented as mean difference for continuous outcomes with 95% confidence intervals whereas risk ratio for binary outcomes., Results: Seven studies were included in the meta-analysis. Based on International Knee Documentation Committee classification, side-to-side difference, Tegner activity score, Lysholm knee score, there were no significant clinical and mechanical differences between the groups., Conclusions: This meta-analysis confirmed that after ACLR, middle age (＞40 years) and young age (＜40 years) patients did not present with significant difference in clinical and arthrometric results.

Purpose: The purpose of this review is to compare the clinical and radiological outcomes between open and closed wedge distal femoral varus osteotomy (DFO)., Methods: A literature search of online databases (MEDLINE, EMBASE, and Cochrane Library database) was made in addition to manual search of major orthopedic journals. Data were searched from the time period of January 1990 to October 2016. A modified Coleman Methodology Score system was used to assess the methodologic quality of the included studies. A total of 20 studies were included in the review. All studies were level IV evidence., Results: Comparative analysis of open and closed wedge DFO did not demonstrate clinical and radiological differences. The survival rates were also similar. Five studies (56%) on open wedge DFO mentioned the need for either bone grafting or substitute for osteotomy gap filling and reported higher incidences of reoperation for plate removal than the closed wedge DFO studies., Conclusions: The present systematic review showed similar performance between open and closed wedge DFO. Outcomes including survival rates were not statistically significantly different. However, additional bone grafting or substitutes were often needed to prevent delayed union or nonunion for open wedge techniques. Additional operations for plate removal were commonly required due to plate irritation in both techniques.

Background: Respiratory syncytial virus (RSV) infection constitutes a substantial disease burden in the general population. However, the risk of death for RSV infection has been rarely evaluated with confounders or comorbidities adjusted. We aimed to evaluate whether RSV infection is associated with higher mortality than seasonal influenza after adjusting for confounders and comorbidities and the effect of oseltamivir on the mortality in patients with influenza infection., Methods: A retrospective cohort study was conducted on adult (≥18 years) patients admitted to the emergency department and ward of a university teaching hospital for suspected viral infection during 2013-2015 (N = 3743). RSV infection was diagnosed by multiplex PCR (N = 87). Adults hospitalized for seasonal influenza during the study period were enrolled as a comparison group (n = 312). The main outcome was 20-day all-cause mortality.We used Cox proportional hazard regression analyses to calculate the relative risk of death., Results: Adult patients were less likely to be diagnosed with RSV than with influenza (2.3 vs 8.3%, respectively), were older and more likely to be diagnosed with pneumonia, chronic obstructive pulmonary disease, hypoxemia, and bacterial co-infection. In patients with RSV infection, the 20-day all-cause mortality was higher than that for influenza, (18.4 vs 6.7%, respectively). RSV infection showed significantly higher risk of death compared to the seasonal influenza group, with hazard ratio, 2.32 (95% CI, 1.17-4.58). Oseltamivir had no significant effect on mortality in patients with influenza., Conclusions: RSV infection was significantly associated with a higher risk of death than seasonal influenza, adjusted for potential confounders and comorbidities.

Background: Composite intestinal adenoma-microcarcinoid (CIAM) is a rare colorectal lesion that mostly comprises a conventional adenomatous component with a minute proportion of neuroendocrine (NE) component. Although microcarcinoids are well-recognized in the setting of chronic inflammatory disorders of the gastrointestinal tract, large intestinal microcarcinoids associated with intestinal adenoma are exceedingly rare and their clinicopathologic characteristics are yet to be elucidated. This study was performed to clarify their clinicopathologic characteristics and to review the relevant literature., Methods: In total, 24 cases of CIAM in which tumors were excised endoscopically (n = 22) or surgically (n = 2) were retrieved from the Department of Pathology, Daehang Hospital. We analyzed their clinicopathologic characteristics and performed immunohistochemical staining for NE markers to determine their endocrine nature., Results: CIAM usually developed in middle-aged and elderly patients, with a mean age of 62.0 years (range, 44-81 years). Thirteen patients were men and 11 were women, indicating a nearly equal sex ratio. Unlike classic carcinoid tumors, CIAMs occurred mostly in the colon (83.3% of cases), particularly in the proximal colon. Histologically, the microcarcinoid component consisted of low-grade NE cells arranged in small nests, glands or cords interspersed with glandular elements or less frequently resembled squamous morules. There was no expansile nodular or organoid growth pattern, which is typical of carcinoid tumors. The microcarcinoids were 1-20 mm in size (mean size, 4.7 mm) and were mostly situated in the basal lamina propria with no submucosal layer involvement; none showed desmoplastic reaction or increased proliferative activity. Follow-up data (mean, 23.1 months) were available for 18 patients; all patients are alive and well., Conclusions: To the best of our knowledge, ours is the largest series of patients with CIAM in the English-language literature. Microcarcinoids found in CIAMs appear to show favorable clinical outcomes regardless of their size, likely due to the absence of submucosal extension and/or increased proliferative activity. We recommend avoiding additional radical surgeries in patients who have endoscopically undergone complete CIAM excision unless they exhibit ominous histologic features such as submucosal extension or increased proliferative activity.

Background: Histologic grade is the most important predictor of the clinical outcome of non-muscle invasive (Ta, T1) papillary urothelial carcinoma (NMIPUCa), but its ambiguous criteria diminish its power to predict recurrence/progression for individual patients. We attempted to find an objective and reproducible histologic predictor of NMIPUCa that correlates well with the clinical outcome., Methods: A total of 296 PUCas were collected from the Departments of Surgical Pathology of 11 institutions in South Korea. The clinical outcome was grouped into no event (NE), recurrence (R), and progression (P) categories. All 25 histological parameters were numerically redefined. The clinical pathology of each case was reviewed individually by 11 pathologists from 11 institutions based on the 2004 WHO criteria and afterwards blindly evaluated by two participants, based on our proposed parameters. Univariate and multivariate logistic regression analyses were performed using the R software package., Results: The level of mitoses was the most reliable parameter for predicting the clinical outcome. We propose a four-tiered grading system based on mitotic count (> 10/10 high-power fields), nuclear pleomorphism (smallest-to-largest ratio of tumor nuclei >20), presence of divergent histology, and capillary proliferation (> 20 capillary lumina per papillary core)., Conclusions: The level of mitoses at the initial bladder biopsy and transurethral resection (TUR) specimen appeared to be an independent predictor of the Ta PUCa outcome. Other parameters include the number of mitoses, nuclear pleomorphism, divergent histology, and capillary proliferation within the fibrovascular core. These findings may improve selection of patients for a therapeutic strategy as compared to previous grading systems.

Background: The impact of meat consumption on high blood pressure (HBP) and obesity in children and adolescents is a subject of debate. The aim of this study was thus to evaluate the association between meat consumption and both HBP and obesity in this group., Methods: We performed a cross-sectional analysis using nationally representative samples of children and adolescents aged 9, 12, and 15 years old (n = 136,739) who were included in the Korea School Health Examination Survey (KSHES) for the 2011-2015 period. Multiple linear and logistic regression analysis was used to determine the factors influencing systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI, kg/m 2 ) levels, and to test the strength of these relationships., Results: Adjusted for covariates, 6.3% of those subjects who consumed >5 servings of meat (including beef, pork, and chicken) per week were obese, compared with 9.1% of the subjects who consumed <1 serving of meat/wk (obesity adjusted odds ratio [OR]: 1.44; 95% confidence interval [CI]: 1.21-1.70; P ≤0.001). Those who consumed <1 serving of meat/wk had an HBP prevalence of 8.2%, compared with 7.2% for subjects who consumed >5 servings of meat/wk (systolic HBP adjusted OR: 1.30; 95% CI: 1.05-1.62; P ≤0.01, diastolic HBP adjusted OR: 1.25; 95% CI: 1.02-1.54; P <0.05). Obese subjects were estimated to have a higher SBP (β = 7.497, P < 0.001) and DBP (β = 4.123, P <0.001) than subjects who had no excess weight. Compared to subjects who consumed >5 servings of meat/wk, those who consumed <3 servings of meat/wk had a higher SBP (β = 0.574, P <0.001) and DBP (β = 0.376, P = 0.003) after adjusting for BMI. The intake of milk, fruit, and vegetables was not associated with either SBP or DBP (P >0.05). In contrast, BMI was significantly associated with milk, fruits, and vegetables (P <0.01)., Conclusions: Among children and adolescents, a higher level of meat consumption was associated with lower SBP, DBP, and BMI, and greater height, suggesting that consuming an appropriate amount of meat is important for healthy growth at a young age.

Robot-assisted gait training (RAGT) after spinal cord injury (SCI) induces several different neurophysiological mechanisms to restore walking ability, including the activation of central pattern generators, task-specific stepping practice and massed exercise. However, there is no clear evidence for the optimal timing and efficacy of RAGT in people with SCI. The aim of our study was to assess the effects of RAGT on improvement in walking-related functional outcomes in patients with incomplete SCI compared with other rehabilitation modalities according to time elapsed since injury. This review included 10 trials involving 502 participants to meta-analysis. The acute RAGT groups showed significantly greater improvements in gait distance, leg strength, and functional level of mobility and independence than the over-ground training (OGT) groups. The pooled mean difference was 45.05 m (95% CI 13.81 to 76.29, P = 0.005, I 2  = 0%; two trials, 122 participants), 2.54 (LEMS, 95% CI 0.11 to 4.96, P = 0.04, I 2  = 0%; three trials, 211 participants) and 0.5 (WISCI-II and FIM-L, 95% CI 0.02 to 0.98, P = 0.04, I 2  = 67%; three trials, 211 participants), respectively. In the chronic RAGT group, significantly greater improvements in speed (pooled mean difference = 0.07 m/s, 95% CI 0.01 to 0.12, P = 0.01, I 2  = 0%; three trials, 124 participants) and balance measured by TUG (pooled mean difference = 9.25, 95% CI 2.76 to 15.73, P = 0.005, I 2  = 74%; three trials, 120 participants) were observed than in the group with no intervention. Thus, RAGT improves mobility-related outcomes to a greater degree than conventional OGT for patients with incomplete SCI, particularly during the acute stage. RAGT treatment is a promising technique to restore functional walking and improve locomotor ability, which might enable SCI patients to maintain a healthy lifestyle and increase their level of physical activity., Trial Registration: PROSPERO (CRD 42016037366 ). Registered 6 April 2016.

Background: The aim of this study is to investigate the physicochemical and structural properties of Medifoam®Silver and to compare with other commercially available silver-containing polyurethane (PU) foam dressing in vitro., Methods: Surface and cross-section of four polyurethane foam dressings were assessed with field-emission scanning electron microscope. Thickness, density, tensile strength, elongation, absorption rate, absorption/retention capacity and water-vapor transmission (WVT) were measured to compare physical properties of various dressing materials., Results: Among four tested dressings, Medifoam®Silver has relatively uniform and smallest pore size in both surface and cross-section. In comparison of absorption properties with other dressing materials, Medifoam®Silver has rapid absorption rate, good absorption/retention capacity and good WVT value., Conclusions: The data further suggests that Medifoam®Silver is a promising candidate for wound healing management.

Background: Pemetrexed is widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSCLC). However, factors that can predict the benefits of pemetrexed therapy have not yet been defined., Methods: We compared the clinical and molecule pathological characteristics of good and poor responders among a cohort of 1,848 non-squamous NSCLC patients who had received at least two cycles of pemetrexed therapy between November 2006 and February 2015. Among these cases, 92 good responders who were the top 5 % in terms of progression-free survival (PFS) and 222 poor responders who had progressive disease after only 2 cycles of therapy were selected for the analysis., Results: The median PFS of the good responders was 29.9 months (range; 20.9-90.0) and the median number of cycle was 37 (range; 18-129). Although 53.5 % of patients showed stable disease (SD), this response was sustained (median PFS in SD, 29.6 months). A never-smoking status was related to better survival outcome, whereas EGFR mutation, two or more metastatic sites, and intra-abdominal metastasis were each associated with a poor PFS. ALK translocation showed a tendency for a positive impact on response to pemetrexed, whereas metastatic lesion to liver, adrenal gland or bone showed a tendency for a negative impact despite not reaching our threshold for statistical significance., Conclusions: Predictive factors, such as smoking status, the status of genetic alteration and tumor burden, should be considered when administering pemetrexed therapy for non-squamous NSCLC.

Background: We investigated the physicochemical properties of Medifoam® N and its wound healing performance compared to other commercially available polyurethane (PU) foam dressing in vitro and in vivo to gain insight in their clinical performance., Methods: Wound contact layer and cross-section of eleven polyurethane foam dressings were assessed with field-emission scanning electron microscope. Thickness, density, tensile strength, elongation, moisture-vapor transmission rate (MVTR), retention and absorptivity were measured to compare physical properties. Phosphate-buffered saline (PBS) solution absorption patterns were compared. An animal model for wound-healing was applied to validate in vitro findings., Results: Among eleven tested foam dressings, Medifoam® N has the smallest pore and cell sizes with excellent uniformity, i.e. it has 25 ~ 75 μm on the wound contact layer and 100 ~ 350 μm in the cross-section while other dressings have a larger pose size with larger variability. Compared to other PU foams, Medifoam® N also has moderate thickness, density, tensile strength, elongation and MVTR. Furthermore, it has excellent fluid absorption and retention capacity. These intrinsic properties of Medifoam® N contributed to improve fluid absorption patterns, i.e. other dressing material flawed out PBS solution on the dressings while Medifoam® N retained all the tested solutions. In animal wound-healing study, Medifoam® N treated animals showed excellent angiogenesis and collagen deposition even though epithelial recovery rate was not significantly different to other dressings., Conclusions: Medifoam® N has optimized physical properties and thus improved fluid absorption/retention capacity. Compared to other dressings, Medifoam® N showed excellent fluid absorption patterns and these characteristics contributed to improved wound healing and excellent angiogenic potential. We found that Medifoam® N showed the best results among the employed dressing samples.

Background: Diabetes mellitus is a disease lack of insulin, which has severely delayed and impaired wound healing capacity. In the previous studies, various types of scaffolds and growth factors were used in impaired wound healing. However, there were several limitations to use them such as short half-life of growth factors in vivo and inadequate experimental conditions of wound-dressing material. Thus, our study aimed to determine the biocompatibility and stability of the matrix containing structurally stabilized epidermal growth factor (S-EGF) and basic fibroblast growth factor (S-bFGF)., Results and Discussion: We stabilized EGF and bFGF that are structurally more stable than existing EGF and bFGF. We developed biocompatible matrix using S-EGF, S-bFGF, and hyaluronate- collagen dressing (HCD) matrix. The developed matrix, S-EGF and S-bFGF loaded on HCD matrix, had no cytotoxicity, in vitro. Also, these matrixes had longer releasing period that result in enhancement of half-life. Finally, when these matrixes were applied on the wound of diabetic mice, there were no inflammatory responses, in vivo. Thus, our results demonstrate that these matrixes are biologically safe and biocompatible as wound-dressing material., Conclusions: Our stabilized EGF and bFGF was more stable than existing EGF and bFGF and the HCD matrix had the capacity to efficiently deliver growth factors. Thus, the S-EGF and S-bFGF loaded on HCD matrix had improved stability. Therefore, these matrixes may be suitable for impaired wound healing, resulting in application of clinical treatment.

Purpose: To summarize and compare radiological and clinical outcomes of open wedge high tibial osteotomy (HTO) using imageless computer-assisted navigation with conventional HTO., Methods: A literature search of online register databases was conducted. The risk ratio (RR) of radiological outliers and mean differences in clinical outcomes were compared between navigated and conventional HTOs. Radiological results were evaluated by subgroup analyses according to the study period (concurrent/consecutive) and the use of locking fixation device., Results: Seven comparative studies with a total sample size of 406 knees were included in this review. Radiographically, the mechanical axis [MA] was within the acceptable range (0°-6°) in 83.7% of the navigation HTO group, showing significant difference from 62.1% of the conventional HTO group. Clinically, despite the forest plot demonstrating a general trend of favoring the navigation system, there were not sufficient studies to determine statistical significance in the meta-analysis. None of the subgroup analyses demonstrated significant differences in the RR of MA outliers., Conclusions: The present meta-analysis indicates that the use of navigation in open wedge HTO improves the precision of mechanical alignment by decreasing the incidence of outliers; however, the clinical benefit is not conclusive. Additionally, none of the subgroup analyses demonstrated significant difference in the RR of MA outliers.

Purpose: Bone grafting in opening wedge high tibial osteotomy (OWHTO) is still controversial. The purpose of this study is to compare the radiological outcomes of OWHTO with bone graft (autogenous, allogenous, and synthetic bone graft) and those without bone graft., Materials and Methods: PubMed, MEDLINE, EMBASE and Cochrane Register of Studies databases were searched using specific inclusion and exclusion criteria for radiological studies involving OWHTO with bone graft and without bone graft groups. All reported delayed union, nonunion and correction loss were analyzed. Data were searched from the time period of January 2000 through July 2014. In addition, a modified Coleman methodology score (CMS) system was used to assess the methodological quality of the included studies., Results: Twenty-five studies with a mean CMS value of 77 (range, 61 to 85 score) were included. In total, 1,841 patients underwent OWHTO using 4 different procedures for bone graft: autobone graft (n=352), allobone graft (n=547), synthetic bone graft (n=541) and no bone graft (n=401). There was a similar tendency for delayed union, nonunion and correction loss rate among the osteotomy space filling methods., Conclusions: The meta-analysis showed there was a similar tendency for radiological union and correction maintenance among patients undergoing OWHTO regardless of the type of bone in all of the studies. However, the currently available evidence is not sufficient to strongly support the superiority of OWHTO with bone graft to OWHTO without bone graft.

Background: Glucose homeostasis is distorted by defects of the PI3K/AKT and AMPK pathways in insulin-sensitive tissues, allowing the accumulation of glucose in the blood. The purpose of this study was to assess the effects and mechanisms by which ethanol extract of Caulerpa lentillifera (CLE) regulates glucose metabolism in C57BL/KsJ-db/db (db/db) mice., Methods: Mice were administered CLE (250 or 500 mg/kg BW) or rosiglitazone (RSG, 10 mg/kg BW) for 6 weeks. Then, oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were performed, and blood glucose was measured in db/db mice. Levels of insulin and insulin resistance factors in plasma, glycogen content in the liver, and IRS, PI3K, AKT, and GLUT4 expressions in skeletal muscles were measured in db/db mice. Glucose uptake and insulin signaling molecules were measured in L6 myocytes, using fluorometry and Western blotting., Results: CLE significantly decreased fasting blood glucose, glucose level in OGTT and IPITT, plasma insulin, homeostatic model assessment-insulin resistant (HOMA-IR), TNF-α, IL-6, FFA, TG and TC levels, and hepatic glycogen content in db/db mice. CLE significantly increased the activation of IRS, AKT, PI3K, and GLUT4, which are the key effector molecules of the PI3K/AKT pathway in L6 myocytes and the skeletal muscles of db/db mice. The enhanced glucose uptake by CLE was abolished by treatment with a PI3K inhibitor (LY294002), but not by an AMPK inhibitor (compound C) in L6 myocytes. CLE regulated glucose uptake and homeostasis via the PI3K/AKT pathway in myocytes and db/db mice, respectively., Conclusion: Our results suggest that CLE could be a potential candidate for the prevention of diabetes.

Introduction: Pectus excavatum is the most common congenital chest wall deformity and the depression of the anterior chest wall, which compresses the internal organs. The aim of the present study is to investigate the effects of pectus excavatum on blood laboratory findings., Material and Methods: From March 2011 to December 2011, 71 patients with pectus excavatum who visited Seoul Saint Mary Hospital for Nuss procedure were reviewed and analyzed. The blood samples were routinely taken at the day before surgery and pectus bar removal was usually performed in 2 to 3 years after Nuss procedure. To investigate the effects on blood laboratory findings, preoperative routine blood laboratory data and postoperative changes of abnormal laboratory data were analyzed., Results: Only lactate dehydrogenase (LDH), one of 26 separate routine laboratory tests, was abnormal and significantly elevated than normal value (age <10, p = 0.008; age ≥10, p < 0.001). However, there was no significant correlation between LDH levels and severities of pectus excavatum. The symmetric subgroup had significantly higher LDH level than the asymmetric subgroup (p < 0.001) and there was a significant decrease of LDH level after correction of deformity (p = 0.017)., Conclusion: In conclusion, only LDH, one of the routine laboratory tests, was significantly elevated than normal value, which was thought to be caused by etiologies of pectus excavatum and the compression of the internal organs. Further studies on LDH including isoenzyme studies in patients with pectus excavatum will be needed, and these studies will provide a deeper and wider comprehension of pectus excavatum.

Background: Studies on the association between obesity and ovarian cancer survival have had conflicting results. We reviewed and quantitatively summarized the existing evidence, exploring potentially important sources of variability, such as the timing of body mass index (BMI) assessment, BMI cut points, references used in multivariate analysis, and ovarian cancer stage., Methods: Eligible studies were searched using MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials, relevant bibliographies were manually reviewed for additional studies. Adjusted hazard ratios (HRs) from individual studies were pooled using a random effects model., Results: 17 cohort studies of 929 screened articles were included in the final analysis. Obesity in early adulthood and obesity 5 years before ovarian cancer diagnosis were associated with poor patient survival (early adulthood: pooled HR 1.67; 95% CI 1.29-2.16; 5 years prediagnosis: pooled HR 1.35; 95% CI 1.03-1.76). However, the results for obesity at diagnosis depended on whether BMI was analyzed as a categorical or continuous variable. Analysis of obesity with BMI as a categorical variable did not affect ovarian cancer prognosis (pooled HR 1.07; 95% CI 0.95-1.21); obesity with BMI as a continuous variable showed slightly poorer survival with each incremental increase in BMI (pooled HR 1.02; 95% CI 1.01-1.04)., Conclusions: Obesity 5 years before ovarian cancer diagnosis and obesity at a young age were associated with poor prognosis. The association between obesity at diagnosis and survival of ovarian cancer patients still remains equivocal. BMI at diagnosis cannot be a prognostic factor for the survival of ovarian cancer patients. Further well-designed studies are needed to elucidate the variety effect of obesity on the survival of ovarian cancer patients.

Background: Lung adenocarcinoma is a highly heterogeneous disease with various etiologies, prognoses, and responses to therapy. Although genome-scale characterization of lung adenocarcinoma has been performed, a comprehensive somatic mutation analysis of EGFR/KRAS/ALK-negative lung adenocarcinoma in never-smokers has not been conducted., Methods: We analyzed whole exome sequencing data from 16 EGFR/KRAS/ALK-negative lung adenocarcinomas and additional 54 tumors in two expansion cohort sets. Candidate loci were validated by target capture and Sanger sequencing. Gene set analysis was performed using Ingenuity Pathway Analysis., Results: We identified 27 genes potentially implicated in the pathogenesis of lung adenocarcinoma. These included targetable genes involved in PI3K/mTOR signaling (TSC1, PIK3CA, AKT2) and receptor tyrosine kinase signaling (ERBB4) and genes not previously highlighted in lung adenocarcinomas, such as SETD2 and PBRM1 (chromatin remodeling), CHEK2 and CDC27 (cell cycle), CUL3 and SOD2 (oxidative stress), and CSMD3 and TFG (immune response). In the expansion cohort (N = 70), TP53 was the most frequently altered gene (11%), followed by SETD2 (6%), CSMD3 (6%), ERBB2 (6%), and CDH10 (4%). In pathway analysis, the majority of altered genes were involved in cell cycle/DNA repair (P <0.001) and cAMP-dependent protein kinase signaling (P <0.001)., Conclusions: The genomic makeup of EGFR/KRAS/ALK-negative lung adenocarcinomas in never-smokers is remarkably diverse. Genes involved in cell cycle regulation/DNA repair are implicated in tumorigenesis and represent potential therapeutic targets.

Background: Several experimental studies in stroke patients suggest that mirror therapy and various virtual reality programs facilitate motor rehabilitation. However, the underlying mechanisms for these therapeutic effects have not been previously described., Objectives: We attempted to delineate the changes in corticospinal excitability when individuals were asked to exercise their upper extremity using a real mirror and virtual mirror. Moreover, we attempted to delineate the role of visual modulation within the virtual environment that affected corticospinal excitability in healthy subjects and stroke patients., Methods: A total of 18 healthy subjects and 18 hemiplegic patients were enrolled into the study. Motor evoked potential (MEP)s from transcranial magnetic stimulation were recorded in the flexor carpi radialis of the non-dominant or affected upper extremity using three different conditions: (A) relaxation; (B) real mirror; and (C) virtual mirror. Moreover, we compared the MEPs from the virtual mirror paradigm using continuous visual feedback or intermittent visual feedback., Results: The rates of amplitude increment and latency decrement of MEPs in both groups were higher during the virtual mirror task than during the real mirror. In healthy subjects and stroke patients, the virtual mirror task with intermittent visual feedback significantly facilitated corticospinal excitability of MEPs compared with continuous visual feedback., Conclusion: Corticospinal excitability was facilitated to a greater extent in the virtual mirror paradigm than in the real mirror and in intermittent visual feedback than in the continuous visual feedback, in both groups. This provides neurophysiological evidence supporting the application of the virtual mirror paradigm using various visual modulation technologies to upper extremity rehabilitation in stroke patients.