Hallym University Medical Center

The normal biochemical reactions in our body, increased exposure to the environment, and higher levels of dietary xenobiotic's result in the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS).

BACKGROUND: An osseous defect of the glenoid rim is sometimes caused by multiple recurrent dislocations of the shoulder. It is generally thought that a large defect should be treated with bone-grafting, but there is a lack of consensus with regard to how large a defect must be in order to necessitate this procedure. Some investigators have proposed that a defect must involve at least one-third of the glenoid surface in order to necessitate bone-grafting. However, it is difficult to determine (1) whether a defect involves one-third of the glenoid surface and (2) whether a defect of this size is critical to the stability of the shoulder after a Bankart repair. The purposes of the present study were (1) to create and quantify various sizes of osseous defects of the glenoid and (2) to determine the effect of such defects on the stability and motion of the shoulder after Bankart repair. METHODS: The glenoids from sixteen dried scapulae were photographed, and the images were scanned into a computer. The average shape of the glenoid was determined on the basis of the scans, and this information was used to design custom templates for the purpose of creating various sizes of osseous defects. Ten fresh-frozen cadaveric shoulders then were obtained from individuals who had been an average of seventy-nine years old at the time of death, and all muscles were removed to expose the joint capsule. With use of a custom multiaxis electromechanical testing machine with a six-degrees-of-freedom load-cell, the humeral head was translated ten millimeters in the anteroinferior direction with the arm in abduction and external rotation as well as in abduction and internal rotation. With a fifty-newton axial force constantly applied to the humerus in order to keep the humeral head centered in the glenoid fossa, the peak force that was needed to translate the humeral head a normalized distance was determined under eleven sequential conditions: (1) with the capsule intact, (2) after the creation of a simulated Bankart lesion, (3) after the capsule was repaired, (4) after the creation of an anteroinferior osseous defect with a width that was 9 percent of the glenoid length (average width, 2.8 millimeters), (5) after the capsule was repaired, (6) after the creation of an osseous defect with a width that was 21 percent of the glenoid length (average width, 6.8 millimeters), (7) after the capsule was repaired, (8) after the creation of an osseous defect with a width that was 34 percent of the glenoid length (average width, 10.8 millimeters), (9) after the capsule was repaired, (10) after the creation of an osseous defect with a width that was 46 percent of the glenoid length (average width, 14.8 millimeters), and (11) after the capsule was repaired. RESULTS: With the arm in abduction and external rotation, the stability of the shoulder after Bankart repair did not change significantly regardless of the size of the osseous defect (p = 0.106). With the arm in abduction and internal rotation, the stability decreased significantly as the size of the osseous defect increased (p<0.0001): the translation force in shoulders in which the width of the osseous defect was at least 21 percent of the glenoid length (average width, 6.8 millimeters) was significantly smaller than the force in shoulders without an osseous defect. The range of external rotation in shoulders in which the width of the osseous defect was at least 21 percent of the glenoid length was significantly less than that in shoulders without a defect (p<0.0001) because of the pretensioning of the capsule caused by closing the gap between the detached capsule and the glenoid rim. The average loss of external rotation was 25 degrees per centimeter of defect. CONCLUSIONS: An osseous defect with a width that is at least 21 percent of the glenoid length may cause instability and limit the range of motion of the shoulder after Bankart repair.

Functional active wound dressings are expected to provide a moist wound environment, offer protection from secondary infections, remove wound exudate and accelerate tissue regeneration, as well as to improve the efficiency of wound healing. Chitosan-based hydrogels are considered as ideal materials for enhancing wound healing owing to their biodegradable, biocompatible, non-toxic, antimicrobial, biologically adhesive, biological activity and hemostatic effects. Chitosan-based hydrogels have been demonstrated to promote wound healing at different wound healing stages, and also can alleviate the factors against wound healing (such as excessive inflammatory and chronic wound infection). The unique biological properties of a chitosan-based hydrogel enable it to serve as both a wound dressing and as a drug delivery system (DDS) to deliver antibacterial agents, growth factors, stem cells and so on, which could further accelerate wound healing. For various kinds of wounds, chitosan-based hydrogels are able to promote the effectiveness of wound healing by modifying or combining with other polymers, and carrying different types of active substances. In this review, we will take a close look at the application of chitosan-based hydrogels in wound dressings and DDS to enhance wound healing.

Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients ('at risk brains') from those with better prognosis or to discriminate Alzheimer's disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing.

BACKGROUND: The potential benefits and risks of the use of dual antiplatelet therapy beyond a 12-month period in patients receiving drug-eluting stents have not been clearly established. METHODS: In two trials, we randomly assigned a total of 2701 patients who had received drug-eluting stents and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary end point was a composite of myocardial infarction or death from cardiac causes. Data from the two trials were merged for analysis. RESULTS: The median duration of follow-up was 19.2 months. The cumulative risk of the primary outcome at 2 years was 1.8% with dual antiplatelet therapy, as compared with 1.2% with aspirin monotherapy (hazard ratio, 1.65; 95% confidence interval [CI], 0.80 to 3.36; P=0.17). The individual risks of myocardial infarction, stroke, stent thrombosis, need for repeat revascularization, major bleeding, and death from any cause did not differ significantly between the two groups. However, in the dual-therapy group as compared with the aspirin-alone group, there was a nonsignificant increase in the composite risk of myocardial infarction, stroke, or death from any cause (hazard ratio, 1.73; 95% CI, 0.99 to 3.00; P=0.051) and in the composite risk of myocardial infarction, stroke, or death from cardiac causes (hazard ratio, 1.84; 95% CI, 0.99 to 3.45; P=0.06). CONCLUSIONS: The use of dual antiplatelet therapy for a period longer than 12 months in patients who had received drug-eluting stents was not significantly more effective than aspirin monotherapy in reducing the rate of myocardial infarction or death from cardiac causes. These findings should be confirmed or refuted through larger, randomized clinical trials with longer-term follow-up. (ClinicalTrials.gov numbers, NCT00484926 and NCT00590174.)

In Brief Objective: To assess the risk factors for clinical anastomotic leakage (AL) in patients undergoing laparoscopic surgery for rectal cancer. Background: Little data are available about risk factors for AL after laparoscopic rectal cancer resection. Methods: This was a retrospective analysis of 1609 patients with rectal cancer who had undergone laparoscopic surgery for rectal cancer with sphincter preservation. Clinical data related to AL were collected from 11 institutions. Univariate and multivariate analyses were performed to determine the risk factors for AL. Results: AL was noted in 101 (6.3%) of the patients. The leakage rate ranged from 2.0% to 10.3% for each hospital (P = 0.04). In patients without protective stomas (n = 1187), male sex [hazard ratio (HR), 3.468], advanced tumor stage (HR, 2.520), lower tumor level (HR, 2.418), preoperative chemoradiation (HR, 6.284), perioperative transfusion (HR, 10.705), and multiple firings of the linear stapler (HR, 6.181) were significantly associated with AL. Our theoretical model suggested that the HR for patients with 2 risk factors was significantly higher than that the HR for patients with no or only 1 risk factor. Conclusions: Male sex, low anastomosis, preoperative chemoradiation, advanced tumor stage, perioperative bleeding, and multiple firings of the linear stapler increased the risk of AL after laparoscopic surgery for rectal cancer. A diverting stoma might be mandatory in patients with 2 or more of the risk factors identified in this analysis. Data are lacking regarding the impact of patient and tumor characteristics on anastomotic dehiscence after laparoscopic rectal excision. In this retrospective analysis of multicenter results, male sex, low-lying rectal tumor, preoperative chemoradiation, perioperative bleeding, and multiple firings of the linear stapler increased the anastomotic leakage risk after laparoscopic surgery for rectal cancer. A diverting stoma might be mandatory in patients with 2 or more risk factors identified in this analysis.

The aim of the Part I of Stroke Statistics in Korea is to summarize nationally representative data of the epidemiology and risk factors of stroke in a single document. Every year, approximately 105,000 people experience a new or recurrent stroke and more than 26,000 die of stroke, which indicates that every 5 minutes stroke attacks someone and every 20 minutes stroke kills someone in Korea. Stroke accounts for roughly 1 of every 10 deaths. The estimated stroke prevalence is about 795,000 in people aged ≥30 years. The nationwide total cost for stroke care was 3,737 billion Korean won (US$3.3 billion) in 2005. Fortunately, the annual stroke mortality rate decreased substantially by 28.3% during the first decade of the 21th century (53.2/100,000 in 2010). Among OECD countries, Korea had the lowest in-hospital 30-day case-fatality rate for ischemic stroke and ranked third lowest for hemorrhagic stroke in 2009. The proportion of ischemic stroke has steadily increased and accounted for 76% of all strokes in 2009. According to hospital registry studies, the 90-day mortality rate was 3-7% for ischemic stroke and 17% for intracerebral hemorrhage. For risk factors, among Korean adults ≥30 years of age, one in 3-4 has hypertension, one in 10 diabetes, and one in 7 hypercholesterolemia. One in 3 Korean adults ≥19 years of age is obese. Over the last 10 years, the prevalence of hypertension slightly decreased, but the prevalence of diabetes, hypercholesterolemia, and obesity increased. Smoking prevalence in men has decreased, but is still as high as 48%. This report could be a valuable resource for establishing health care policy and guiding future research directions.

STUDY DESIGN: A prospective radiographic study. OBJECTIVES: To analyze the relationship between craniocervical sagittal balance and thoracic inlet (TI) alignment and to present the parameters that would help predict physiological lordosis of the cervical spine. SUMMARY OF BACKGROUND DATA: The physiological cervical lordosis (CL) and related factors has not been clearly defined yet. No studies have reported correlations between TI alignment and sagittal balance of the cervical spine. METHODS: Cervical spine lateral radiograph of 77 asymptomatic adult volunteers (aged between 21 and 50 y) were taken to analyze the following parameters. (1) Thoracic inlet parameters: thoracic inlet angle (TIA), T1 slope, neck tilting (NT); (2) cervical spine parameters: C0-2 angle, C2-7 angle, % ratio of (C0-2/C0-7 angle), (C2-7/C0-7 angle), and cervical tilting; (3) cranial parameters: C0 angle, cranial offset, and cranial tilting. Statistical analysis was performed using the Pearson correlation coefficients and multiple regression analysis. RESULTS: The mean TIA, T1 slope, NT were 69.5, 25.7, and 43.7, respectively. The mean C0-2 angle, C2-7 angle, C0 angle, cranial offset, cervical tilting, and cranial tilting were -22.4 degrees, -9.9 degrees, -9.3 degrees, 20.9 mm, 18 degrees, and 7.7 degrees, respectively. The ratio of C0-2:C2-7 angle was maintained as 77:23% and cervical tilting:cranial tilting was 70.2:29.8%. A significant correlation was found between TIA and T1 slope (r=0.694), T1 slope and C2-7 angle (r=-0.624), C2-7 angle and C0-2 angle (r=-0.547), C0-2 angle and cranial offset (r=-0.406). CONCLUSIONS: The thoracic inlet alignment had significant correlations with craniocervical sagittal balance. To preserve physiological NT around 44 degrees, large TIA increased T1 slope and CL and vice versa. TIA and T1 slope could be used as parameters to predict physiological alignment of the cervical spine. The results of this study may serve as baseline data for the evaluation of sagittal balance or planning of a fusion angle in the cervical spine.

Atherosclerosis is a chronic progressive vascular disease. It starts early in life, has a long asymptomatic phase, and a progression accelerated by various cardiovascular risk factors. The endothelium is an active inner layer of the blood vessel. It generates many factors that regulate vascular tone, the adhesion of circulating blood cells, smooth muscle proliferation, and inflammation, which are the key mechanisms of atherosclerosis and can contribute to the development of cardiovascular events. There is growing evidence that functional impairment of the endothelium is one of the first recognizable signs of development of atherosclerosis and is present long before the occurrence of atherosclerotic cardiovascular disease. Therefore, understanding the endothelium's central role provides not only insights into pathophysiology, but also a possible clinical opportunity to detect early disease, stratify cardiovascular risk, and assess response to treatments. In the present review, we will discuss the clinical implications of endothelial function as well as the therapeutic issues for endothelial dysfunction in cardiovascular disease as primary and secondary endothelial therapy.

OBJECTIVE: To compare short-term surgical outcomes including financial cost of robotic and laparoscopic gastrectomy. BACKGROUND: Despite a lack of supporting evidence, robotic surgery has been increasingly adopted as a minimally invasive modality for the treatment of gastric cancer because of its assumed technical superiority over conventional laparoscopy. METHODS: A prospective, multicenter comparative study was conducted. Patients were matched according to the surgeon, extent of gastric resection, and sex. The primary endpoint was morbidity and mortality. Outcomes were analyzed on an intention-to-treat and per-protocol basis. RESULTS: A total of 434 patients were enrolled for treatment with either robotic (n = 223) or laparoscopic (n = 211) gastrectomy for intention-to-treat analysis, and a total of 370 patients (n = 185 per treatment) were compared in per-protocol analysis. Results were similar between both analyses. In per-protocol analysis, both groups showed similar overall complication rates (robotic = 11.9% vs laparoscopic = 10.3%) and major complication rates (robotic = 1.1% vs laparoscopic = 1.1%) with no operative mortality in either group. Patients treated with robotic surgery showed significantly longer operative time (robotic = 221 minutes vs laparoscopic = 178 minutes; P < 0.001) and significantly higher total costs (robotic = US$13,432 vs laparoscopic = US$8090; P < 0.001), compared with those who underwent laparoscopic gastrectomy. No significant differences between groups were noted in estimated blood loss, rates of open conversion, diet build-up, or length of hospital stay. CONCLUSIONS: The use of robotic systems is assumed to provide a technically superior operative environment for minimally invasive surgery. However, our analysis of perioperative surgical outcomes indicated that robotic gastrectomy is not superior to laparoscopic gastrectomy. Clinical trials identification: NCT01309256.

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

•In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy.•The addition of radiotherapy to chemotherapy did not significantly reduce the rate of recurrence after D2 gastrectomy.•DFS between patients treated with adjuvant chemotherapy and chemoradiotherapy was similar across all subgroups, including Lauren classification. BackgroundAdjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC.Patients and methodsThe ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146).ResultsA total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable.ConclusionsIn patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy. Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

BACKGROUND: Fucoidan is a sulfated polysaccharide found in brown algae; it has been shown to exhibit a number of biological effects, including anti-tumor effects. In this study, we evaluated the effects of fucoidan on apoptosis in HT-29 and HCT116 human colon cancer cells. METHODS: HT-29 and HCT116 cells were cultured with various concentrations of fucoidan (0 - 20 microg/mL). Apoptosis was assayed via Hoechst staining and Annexin V staining followed by flow cytometric analysis. Western blot analyses and JC-1 staining were conducted to determine the levels of apoptosis-regulating proteins and mitochondrial membrane permeability, respectively. RESULTS: Fucoidan induced substantial reductions in viable cell numbers and apoptosis of HT-29 and HCT116 cells in a dose-dependent manner. In HT-29 cells, fucoidan also increased the levels of cleaved caspases-8, -9, -7, and -3, and cleaved poly (ADP-ribose) polymerase (PARP) levels. The levels of the X-linked inhibitor of apoptosis protein and survivin were attenuated in the fucoidan-treated cells. Fucoidan was also shown to enhance mitochondrial membrane permeability, as well as the cytochrome c and Smac/Diablo release from the mitochondria. Fucoidan increased the levels of the Bak and truncated Bid proteins, but reduced the levels of Mcl-1. Additionally, fucoidan increased the levels of the tumor necrosis factor-related apoptosis-inducing ligand, Fas and death receptor 5 proteins. The caspase-8 and -9 inhibitors Z-IETD-FMK and Z-LEHD-FMK induced a reduction in fucoidan-mediated apoptosis. Caspase-8 inhibitor inhibited the fucoidan-induced cleavage of Bid, caspases-9 and -3, and PARP. CONCLUSION: The findings of this study indicate that fucoidan induces apoptosis in HT-29 and HCT116 human colon cancer cells, and that this phenomenon is mediated via both the death receptor-mediated and mitochondria-mediated apoptotic pathways. These results suggest that fucoidan may prove useful in the development of a colon cancer-preventive protocol.

Biomarkers play a vital role in disease detection and treatment follow-up. It is important to note that diseases in the early stage are typically treated with the greatest probability of success. However, due to various technical difficulties in current technologies for the detection of biomarkers, the potential of biomarkers is not explored completely. Therefore, the developments of technologies, which can enable the accurate detection of prostate cancer at an early stage with simple, experimental protocols are highly inevitable. This critical review evaluates the current methods and technologies used in the detection of biomarkers. The aim of this article is to provide a comprehensive review covering the advantages and disadvantages of the biomarker detection methods. Future directions for the development of technologies to achieve highly selective and sensitive detection of biomarkers for point-of-care applications are also commented on.

beta-Carotene has shown antioxidant and anti-inflammatory activities; however, its molecular mechanism has not been clearly defined. We examined in vitro and in vivo regulatory function of beta-carotene on the production of nitric oxide (NO) and PGE(2) as well as expression of inducible NO synthase (iNOS), cyclooxygenase-2, TNF-alpha, and IL-1beta. beta-Carotene inhibited the expression and production of these inflammatory mediators in both LPS-stimulated RAW264.7 cells and primary macrophages in a dose-dependent fashion as well as in LPS-administrated mice. Furthermore, this compound suppressed NF-kappaB activation and iNOS promoter activity in RAW264.7 cells stimulated with LPS. beta-Carotene blocked nuclear translocation of NF-kappaB p65 subunit, which correlated with its inhibitory effect on IkappaBalpha phosphorylation and degradation. This compound directly blocked the intracellular accumulation of reactive oxygen species in RAW264.7 cells stimulated with LPS as both the NADPH oxidase inhibitor diphenylene iodonium and antioxidant pyrrolidine dithiocarbamate did. The inhibition of NADPH oxidase also inhibited NO production, iNOS expression, and iNOS promoter activity. These results suggest that beta-carotene possesses anti-inflammatory activity by functioning as a potential inhibitor for redox-based NF-kappaB activation, probably due to its antioxidant activity.

BACKGROUND: Thyroid ultrasound (US) is used as the first diagnostic tool to assess the management of the disease. In spite of its importance, US is a very subjective method and highly dependent on the skill of the performer. There have been few reports evaluating thyroid US performance and even fewer reports of observer variability in US assessment. Therefore, we evaluated inter- and intraobserver variations in US assessment of thyroid nodules and diagnosis among four radiologists and estimated its diagnostic accuracy. METHODS: A total of 204 thyroid nodules in 144 patients were reviewed. There were 89 benign and 115 malignant cases. Four radiologists with more than 5 years of experience independently reviewed US images twice at 6-week intervals. Echogenicity, composition, margin, shape, calcification, vascularity, and final assessment were evaluated. Inter- and intraobserver variations were determined with Cohen's kappa statistics, and accuracy was calculated. RESULTS: For interobserver variations, echogenicity showed slight agreement (kappa = 0.34); composition, margin, calcification, and final assessment had fair agreement (kappa = 0.59, 0.42, 0.58, and 0.54, respectively); shape and vascularity showed substantial agreement (kappa = 0.61 and 0.64, respectively). For intraobserver variability, almost all showed substantial agreement (kappa > 0.61). Overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the four radiologists were 88.2%, 78.7%, 76.2%, 89.6%, and 82.8%, respectively. CONCLUSIONS: Experienced radiologists showed more than a moderate degree of agreement in US assessment of thyroid nodules, and their final assessments were highly accurate.

We have provided an overview on the profound impact of COVID-19 upon older people with Alzheimer's disease and other dementias and the challenges encountered in our management of dementia in different health-care settings, including hospital, out-patient, care homes, and the community during the COVID-19 pandemic. We have also proposed a conceptual framework and practical suggestions for health-care providers in tackling these challenges, which can also apply to the care of older people in general, with or without other neurological diseases, such as stroke or parkinsonism. We believe this review will provide strategic directions and set standards for health-care leaders in dementia, including governmental bodies around the world in coordinating emergency response plans for protecting and caring for older people with dementia amid the COIVD-19 outbreak, which is likely to continue at varying severity in different regions around the world in the medium term.

// Xiaoliang Wu 1, * , Xuewen Liu 1, 2, * , Sanjay Koul 2, * , Chang Youl Lee 3 , Zhenfeng Zhang 1 , Balazs Halmos 2 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People&rsquo;s Republic of China 2 Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, New York Presbyterian Hospital-Columbia University Medical Center, New York, NY, USA 3 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chuncheon Sacred Heart Hospital Hallym University Medical Center, Chuncheon-si Gangwon-do 200&ndash;704 Republic of Korea * These authors contributed equally to this work Correspondence to: Zhenfeng Zhang, e-mail: zhangzhf@sysucc.org.cn Balazs Halmos, e-mail: bh2376@columbia.edu Keywords: AXL, receptor tyrosine kinase, lung cancer, targeted therapy. Received: July 23, 2014&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: September 29, 2014&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: October 16, 2014 ABSTRACT The AXL receptor tyrosine kinase and its major ligand, GAS6 have been demonstrated to be overexpressed and activated in many human cancers (such as lung, breast, and pancreatic cancer) and have been correlated with poor prognosis, promotion of increased invasiveness/metastasis, the EMT phenotype and drug resistance. Targeting AXL in different model systems with specific small molecule kinase inhibitors or antibodies alone or in combination with other drugs can lead to inactivation of AXL-mediated signaling pathways and can lead to regained drug sensitivity and improved therapeutic efficacy, defining AXL as a promising novel target for cancer therapeutics. This review highlights the data supporting AXL as a novel treatment candidate in a variety of cancers as well as the current status of drug development targeting the AXL/GAS6 axis and future perspectives in this emerging field.

OBJECTIVE: To determine the immunologic effects of oropharyngeal colostrum administration in extremely premature infants. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving 48 preterm infants born before 28 weeks' gestation. Subjects received 0.2 mL of their mother's colostrum or sterile water via oropharyngeal route every 3 hours for 3 days beginning at 48 to 96 hours of life. To measure concentrations of secretory immunoglobulin A, lactoferrin, and several immune substances, urine and saliva were obtained during the first 24 hours of life and at 8 and 15 days. Clinical data during hospitalization were collected. RESULTS: Urinary levels of secretory immunoglobulin A at 1 week (71.4 vs 26.5 ng/g creatinine, P = .04) and 2 weeks (233.8 vs 48.3 ng/g creatinine, P = .006), and lactoferrin at 1 week (3.5 vs 0.9 μg/g creatinine, P = .01) were significantly higher in colostrum group. Urine interleukin-1β level was significantly lower in colostrum group at 2 weeks (55.3 vs 91.8 μg/g creatinine, P = .01). Salivary transforming growth factor-β1 (39.2 vs 69.7 μg/mL, P = .03) and interleukin-8 (1.2 vs 4.9 ng/mL, P = .04) were significantly lower at 2 weeks in colostrum group. A significant reduction in the incidence of clinical sepsis was noted in colostrum group (50% vs 92%, P = .003). CONCLUSIONS: This study suggests that oropharyngeal administration of colostrum may decrease clinical sepsis, inhibit secretion of pro-inflammatory cytokines, and increase levels of circulating immune-protective factors in extremely premature infants. Larger studies to confirm these findings are warranted.

The Korean College of Helicobacter and Upper Gastrointestinal Research first developed guidelines for the diagnosis and treatment of Helicobacter pylori (H. pylori) infection in 1998, and revised guidelines were proposed in 2009 by the same group. Although the revised guidelines were based on a comprehensive review of published articles and the consensus of expert opinions, the revised guidelines were not developed using an evidence-based process. The new guidelines presented in this study include specific changes regarding indication and treatment of H. pylori infection in Korea, and were developed through the adaptation process using an evidence-based approach. After systematic review of the literature, six guidelines were selected using the Appraisal of Guidelines for Research and Evaluation (AGREE) II process. A total of 21 statements were proposed with the grading system and revised using the modified Delphi method. After the guideline revisions, 11 statements about indication of test and treatment, four statements about diagnosis, and four statements about treatment of H. pylori infection were developed. The revised guidelines were reviewed by external experts before receiving official endorsement from the Korean College of Helicobacter and Upper Gastrointestinal Research, and disseminated to physicians and other medical professionals for use in clinical practice in Korea. The guidelines will continue to be updated and revised periodically.