Aedes aegypti larval indices and risk for dengue epidemics.
We assessed in a case-control study the test-validity of Aedes larval indices for the 2000 Havana outbreak. "Cases" were blocks where a dengue fever patient lived during the outbreak. "Controls" were randomly sampled blocks. Before, during, and after the epidemic, we calculated Breteau index (BI) and house index at the area, neighborhood, and block level. We constructed receiver operating characteristic (ROC) curves to determine their performance as predictors of dengue transmission. We observed a pronounced effect of the level of measurement. The BI(max) (maximum block BI in a radius of 100 m) at 2-month intervals had an area under the ROC curve of 71%. At a cutoff of 4.0, it significantly (odds ratio 6.00, p<0.05) predicted transmission with 78% sensitivity and 63% specificity. Analysis of BI at the local level, with human-defined boundaries, could be introduced in control programs to identify neighborhoods at high risk for dengue transmission.


Social support and problem-solving as moderators of the relationship between childhood abuse and suicidality: applications to a delinquent population.
The purpose of the current study was to examine the relationship between childhood abuse, social support, and problem-solving appraisal within a juvenile delinquent sample. Hierarchical regression analyses were used to assess whether childhood abuse, social support, and problem-solving appraisal were independently predictive of suicidality, and further, whetherproblem-solving appraisal and social support moderated the childhood abuse-suicidality relationship. Childhood sexual abuse was found to be an independent predictor of suicidal ideation and behavior. In addition, both problem-solving confidence and social support moderated the relationship between childhood abuse and suicidal ideation. The results of this study underscore the importance of both problem-solving appraisal and social support to suicidality in adolescents with a history of abuse.


Hemodynamic effects of BTS 49465, a new long-acting systemic vasodilator drug, in patients with severe congestive heart failure.
The hemodynamic effects of BTS 49465, a new oral, direct-acting systemic vasodilator drug, were investigated in 10 patients with severe chronic congestive heart failure. One to 2 hours after the administration of 1.5 mg/kg orally, BTS 49465 produced significant increases in cardiac index, stroke volume index, and stroke work index (26%, 27%, and 23%, respectively, p less than 0.01 to 0.001) and marked decreases in left ventricular filling pressure (-12.6 mm Hg, 44%), mean pulmonary artery pressure (-13.2 mm Hg, 31%), and mean right atrial pressure (-7.7 mm Hg, 63%), all p less than 0.001, without significant changes in heart rate. These hemodynamic responses were accompanied by notable declines in systemic vascular resistance (-28%, p less than 0.001) and pulmonary arteriolar resistance (-24%, p less than 0.05). These effects persisted throughout the 24-hour period of observation. The decline in left ventricular filling pressure in our patients ranged in magnitude from 8 to 21 mm Hg, and varied linearly and directly with pretreatment values for left ventricular filling pressure (r = 0.69). The decrease in systemic vascular resistance ranged in magnitude from 3% to 40% and varied linearly and directly with pretreatment values for systemic vascular resistance (r = 0.85). These data indicate that BTS 49465, a new oral, direct-acting vasodilator agent, exerts balanced cardiocirculatory effects in patients with severe chronic heart failure, which may be sustained with once-daily oral administration.


Association Between Educational Attainment and EFNEP Participants' Food Practice Outcomes.
Examine the association between educational attainment and improvement in food practice outcomes of the California Expanded Food and Nutrition Education Program (EFNEP) participants. Secondary data analysis. A total of 19,089 participants, 92.3% female, 77.2% Hispanic, 19.7% with ≤ sixth-grade education, and 68.9% with incomes ≤ 100% of the federal poverty level. Improvement in food resource management practices (FRMP), nutrition practices, and food safety practices (FSP). Wilcoxon signed rank tests examined pre-post outcomes. Mann-Whitney U tests compared whether participants in the lowest and highest educational attainment quartiles had similar levels of improvement. California EFNEP is associated with improved FRMP (z = -95.33), nutrition practices (z = -94.91), and FSP (z = -92.37); (P < 0.001). Lowest educational quartile was associated with more improvement in FRMP and FSP (P < 0.001). California EFNEP contributed to improved food practice outcomes for low and high educational attainment participants. Program content and instruction are effective across the education continuum.


Culture and mental health resilience in times of COVID-19.
This paper aims to clarify the role of culture as a public good that serves to preserve mental health. It tests the evolutionary hypothesis that cultural consumption triggers a microeconomic mechanism for the self-defense of mental health from uncertainty. The COVID-19 pandemic offers a natural experiment of cultural consumption under increased uncertainty. Using primary data from a pilot survey conducted online during the pandemic and applying Probit and Heckman selection models, the study analyzes levels of happiness and propensity to help others. The results suggest that past consumption of culture is associated with higher happiness levels during crises. Moreover, spontaneous cultural practices (such as group singing) during times of uncertainty are associated with an increase in the pro-social propensity to help others. These findings highlight culture as a tool for promoting mental health at the micro level and social capital resilience at the aggregate level.


'A limpet on a ship': Spatio-temporal dynamics of patient and public involvement in research.
To understand how current funding expectations that applied health research is undertaken in partnership with research institutions, health service providers and other stakeholders may impact on patient and public involvement (PPI). While there is considerable research on the potential impact of PPI in health research, the processes of embedding PPI in research teams remain understudied. We draw on anthropological research on meetings as sites of production and reproduction of institutional cultures and external contexts to investigate how these functions of meetings may affect the potential contributions of patients, carers and the public in research. We present an ethnography of meetings that draws from a larger set of case studies of PPI in applied health research settings. The study draws on ethnographic observations, interviews with team members, analysis of documents and a presentation of preliminary findings through which feedback from informants was gathered. We identified four means by which the oversight meetings regulated research and constrained the possibilities for PPI: a logic of 'deliverables' and imagined interlocutors, the performance of inclusion, positioning PPI in an 'elsewhere' of research, and the use of meetings to embed apprenticeship for junior researchers. PPI is essentially out of sync from the institutional logic of 'deliverables' constituting research partnerships. Embedding PPI in research requires challenging this logic.


Evaluation of the relationship between previous statin use and thyroid cancer using Korean National Health Insurance Service-Health Screening Cohort data.
The association of thyroid cancer with statin use is controversial. This study aimed to investigate the association of previous statin use with thyroid cancer in the ≥ 40-year-old population in the Korean National Health Insurance Service-Health Screening Cohort. The 5501 patients in the thyroid cancer group were matched with the 22,004 patients in the non-thyroid cancer group for age, sex, income, and region of residence. Previous statin use during the 2 years before the diagnosis of thyroid cancer was examined. The odds ratios (ORs) with 95% confidence intervals (CIs) of previous statin use for thyroid cancer were estimated using conditional logistic regression analyses. Additionally, subgroup analyses were conducted. The thyroid cancer group showed more days of previous statin use than the non-thyroid cancer group (72.3, standard deviation [SD] = 181.2 days vs. 64.3, SD = 174.4 days, P = 0.003). Although the odds of previous statin use for thyroid cancer were high in the crude model (OR = 1.10, 95% CI 1.04-1.17, P = 0.002), they were low in the fully adjusted model (OR = 0.89, 95% CI 0.82-0.95, P = 0.001). According to age and sex subgroups, the younger (< 60 years old) male group showed lower odds for thyroid cancer according to previous statin use (adjusted OR = 0.70, 95% CI 0.55-0.88, P = 0.003), but this finding was not observed in other subgroups of older men or in any groups of women. Thyroid cancer was negatively associated with statin use in the previous 2 years in the adjusted model.


Preoperative prediction of regional lymph node metastasis of colorectal cancer based on 18F-FDG PET/CT and machine learning.
To establish and validate a regional lymph node (LN) metastasis prediction model of colorectal cancer (CRC) based on 18F-FDG PET/CT and radiomic features using machine-learning methods. A total of 199 colorectal cancer patients underwent pre-therapy diagnostic 18F-FDG PET/CT scans and CRC radical surgery. The Chang-Gung Image Texture Analysis toolbox (CGITA) was used to extract 70 PET radiomic features reflecting 18F-FDG uptake heterogeneity of tumors. The least absolute shrinkage and selection operator (LASSO) algorithm was used to select radiomic features and develop a radiomic signature score (Rad-score). The training set was used to establish five machine-learning prediction models and the test set was used to test the efficacy of the models. The effectiveness of the models was compared by ROC analysis. The CRC patients were divided into a training set (n = 144) and a test set (n = 55). Two radiomic features were selected to build the Rad-score. Five machine-learning algorithms including logistic regression, support vector machine (SVM), random forest, neural network and eXtreme gradient boosting (XGBoost) were used to established models. Among the five machine-learning models, logistic regression (AUC 0.866, 95% CI 0.808-0.925) and XGBoost (AUC 0.903, 95% CI 0.855-0.951) models performed the best. In the training set, the AUC of these two models were significantly higher than that of the LN metastasis status reported by 18F-FDG PET/CT for differentiating positive and negative regional LN metastases in CRC (all p < 0.05). Good efficacy of the above two models was also achieved in the test set. We created a nomogram based on the logistic regression model that visualized the results and provided an easy-to-use method for predicting regional LN metastasis in patients with CRC. In this study, five machine-learning models for preoperative prediction of regional LN metastasis of CRC based on 18F-FDG PET/CT and PET-based radiomic features were successfully developed and validated. Among them, the logistic regression and XGBoost models performed the best, with higher efficacy than 18F-FDG PET/CT in both the training and test sets.


Comparison of 7-day and repeated 24-h recall of type 2 diabetes.
Patient reporting of type 2 diabetes symptoms in a questionnaire with a 7-day recall period was expected to be different from symptom reports using a 7-day diary with repeated 24-h recall based on cognitive theory of memory processes and prior literature. This study compared these two types of recall in patients diagnosed with type 2 diabetes (T2D). One hundred and forty adults with T2D completed a daily diary for 7 days containing 9 T2D-related symptom and impact items. On day 7, patients completed the same items with a 7-day recall period. We examined the concordance of 7-day recall with summary descriptors of the daily reports and compared the scores and the discriminant ability of 7-day recall and mean of daily reports. Seven-day recall was most concordant with the mean of daily reports. The average difference in scores was small (range 0.22-0.77 on 11-point scale) and less than 0.5 standard deviations. For some items, the difference was positively associated with the variation in daily reports. The discriminant ability was comparable. In this study population, a questionnaire with 7-day recall provided information consistent with a daily diary measure of the average week-long experience of T2D symptoms and impacts.


Histopathological Chromogranin A-Positivity Is Associated with Right-Sided Colorectal Cancers and Worse Prognosis.
Colorectal cancer (CRC) is known to be affected by paraneoplastic thrombocytosis and chromogranin A-positive neuroendocrine-cell differentiation (CgA+). Their combined effect has never been previously investigated. A prospective cohort pilot study of 42 CRC patients and 42 age- and sex-matched controls was carried out. Plasma interleukin-6, thrombopoietin, and serum chromogranin A and -B were measured; furthermore, tumor tissue was immunohistochemically stained for CgA+. Twenty-seven and 15 patients were assigned to the chromogranin A-negative (CgA-) and CgA+ groups, respectively. Within the CgA+ group, right-sided tumors were more frequent (18.5% vs. 53.3%), no stage I cancer was found, and patients of this group were in worse general condition. Compared to control subjects, chromogranin A level was higher in the CgA+ group (p = 0.0086), thrombopoietin (p = 0.0040) and chromogranin B (p = 0.0070) in the CgA- group, while interleukin-6 was high in both tumor groups (p ≤ 0.0090). Survival was significantly worse in the CgA+ group (hazard ratio: 5.73; p = 0.0378). Different thrombopoietin levels indicated distinct thrombocytosis types. Within the two CRC groups, serum levels of chromogranins changed in different directions suggesting two well-distinguishable pathophysiologies. Based on these observations we propose a new subtype of CRC, which can be characterized by chromogranin A-positive neuroendocrine-cell differentiation.


Cross-sectional evaluation of transmural healing in patients with Crohn's disease on maintenance treatment with anti-TNF alpha agents.
Transmural healing (TH) of Crohn's disease (CD) is a still unexplored and interesting outcome correlated to concept of deep remission. To assess the rate of TH in CD patients treated with anti-TNF alpha agents using two cross-sectional procedures: bowel sonography (BS) and magnetic resonance enterography (MRE). We performed a 2-year observational longitudinal study, evaluating steroid-free clinical remission (CR), mucosal healing (MH), and TH in CD patients who would complete a 2-year treatment period with anti-TNFs. All patients underwent endoscopy, BS, and MRE before and after 2 years of treatment. Forty out of 80 CD patients were treated with anti-TNFs for 2 years. CR was achieved in 24 patients (60%) while MH in 14 (35%). Using BS, TH was observed in 10 patients (25%), while using MRE, TH was observed in 9 patients (23%) (k=0.90; P<0.01). A good agreement was observed between MH and TH, both using BS (k=0.63; P<0.01) and MRE (k=0.64; P<0.01). A poor agreement was found between CR and TH, with both BS and MRE (k=0.27 and 0.29, respectively; P<0.01); even though all patients with TH had achieved CR. TH can be achieved in about 25% of CD patients treated with anti-TNFs, as shown by BS and MRE. BS could be used as the first cross-sectional procedure to detect TH.


Dealloying-Derived Nanoporous Cu6Sn5 Alloy as Stable Anode Materials for Lithium-Ion Batteries.
The volume expansion during Li ion insertion/extraction remains an obstacle for the application of Sn-based anode in lithium ion-batteries. Herein, the nanoporous (np) Cu6Sn5 alloy and Cu6Sn5/Sn composite were applied as a lithium-ion battery anode. The as-dealloyed np-Cu6Sn5 has an ultrafine ligament size of 40 nm and a high BET-specific area of 15.9 m2 g-1. The anode shows an initial discharge capacity as high as 1200 mA h g-1, and it remains a capacity of higher than 600 mA h g-1 for the initial five cycles at 0.1 A g-1. After 100 cycles, the anode maintains a stable capacity higher than 200 mA h g-1 for at least 350 cycles, with outstanding Coulombic efficiency. The ex situ XRD patterns reveal the reverse phase transformation between Cu6Sn5 and Li2CuSn. The Cu6Sn5/Sn composite presents a similar cycling performance with a slightly inferior rate performance compared to np-Cu6Sn5. The study demonstrates that dealloyed nanoporous Cu6Sn5 alloy could be a promising candidate for lithium-ion batteries.


Design of Factor XIII V34X activation peptides to control ability to interact with thrombin mutants.
Thrombin helps to activate Factor XIII (FXIII) by hydrolyzing the R37-G38 peptide bond. The resultant transglutaminase introduces cross-links into the fibrin clot. With the development of therapeutic coagulation factors, there is a need to better understand interactions involving FXIII. Such knowledge will help predict ability to activate FXIII and thus ability to promote/hinder the generation of transglutaminase activity. Kinetic parameters have been determined for a series of thrombin species hydrolyzing the FXIII (28-41) V34X activation peptides (V34, V34L, V34F, and V34P). The V34P substitution introduces PAR4 character into the FXIII, and the V34F exhibits important similarities to the cardioprotective V34L. FXIII activation peptides containing V34, V34L, or V34P could each be accommodated by alanine mutants of thrombin lacking either the W60d or Y60a residue in the 60-insertion loop. By contrast, FXIII V34F AP could be cleaved by thrombin W60dA but not by Y60aA. FXIII V34P is highly reliant on the thrombin W215 platform for its strong substrate properties whereas FXIII V34F AP becomes the first segment that can maintain its K(m) upon loss of the critical thrombin W215 residue. Interestingly, FXIII V34F AP could also be readily accommodated by thrombin L99A and E217A. Hydrolysis of FXIII V34F AP by thrombin W217A/E217A (WE) was similar to that of FXIII V34L AP whereas WE could not effectively cleave FXIII V34P AP. FXIII V34F and V34P AP show promise for designing FXIII activation systems that are either tolerant of or greatly hindered by the presence of anticoagulant thrombins.


Role of methyl salicylate on oviposition deterrence in Arabidopsis thaliana.
Plants attacked by herbivores have evolved different strategies that fend off their enemies. Insect eggs deposited on leaves have been shown to inhibit further oviposition through visual or chemical cues. In some plant species, the volatile methyl salicylate (MeSA) repels gravid insects but whether it plays the same role in the model species Arabidopsis thaliana is currently unknown. Here we showed that Pieris brassicae butterflies laid fewer eggs on Arabidopsis plants that were next to a MeSA dispenser or on plants with constitutively high MeSA emission than on control plants. Surprisingly, the MeSA biosynthesis mutant bsmt1-1 treated with egg extract was still repellent to butterflies when compared to untreated bsmt1-1. Moreover, the expression of BSMT1 was not enhanced by egg extract treatment but was induced by herbivory. Altogether, these results provide evidence that the deterring activity of eggs on gravid butterflies is independent of MeSA emission in Arabidopsis, and that MeSA might rather serve as a deterrent in plants challenged by feeding larvae.


Resilience, pain, and health-related quality of life in gynecological patients undergoing surgery for benign and malignant conditions: a 12-month follow-up study.
Gynecological surgery has many impacts on women's physical and mental health, and efforts to improve recovery from surgery are constantly under evaluation. Resilience is an ability to overcome stressors and adversities, such as traumas and surgeries. This study aimed to explore patients' resilience and psychological symptoms in relation to recovery, health-related quality of life (HRQoL), and pain one year after gynecological surgery. In a prospective cohort study, we enrolled consecutive elective gynecologic surgery patients who completed questionnaires before and at one year after surgery: the Resilience Scale-25, the 15D instrument of HRQoL (15D), the Life Satisfaction Scale-4, and the Hospital Anxiety and Depression Scale. Their mean 15D scores were compared to those of an age-matched sample of women from the general Finnish population (n = 2743). We enrolled 271 women who underwent gynecological surgery due to benign (n = 190) and malignant (n = 81) diagnoses. Resilience was equally high in women with benign and malignant diagnoses at both time points. Higher resilience associated with less pain, analgesic use, and better pain relief from the use of pain medication at 12 months after surgery. Pain intensity was similar in the two groups, but patients with benign diseases had less pain at 12 months than before surgery. Before surgery, patients' HRQoL was worse than that of the general population, but at 12 months the mean HRQoL of patients with benign diseases had improved to the same level as that in the general population but had decreased further in patients with malignant diseases. Anxiety was higher and life satisfaction was lower in patients with malignant diseases before surgery. At 12 months, anxiety had decreased in both groups, and life satisfaction had increased in patients with malignant diseases. Depression was similarly low in both groups and time points. Resilience correlated with less pain one year after surgery. After surgery, HRQoL improved in patients with benign diseases but deteriorated in patients with malignant diseases. Patients with low resilience should be identified during preoperative evaluation, and health care professionals should give these patients psychological support to enhance their resilience. Trial Registration ClinicalTrials.gov; registered October 29, 2019; identifier: NCT04142203; retrospectively registered.


Colonic mucosal changes in patients with liver cirrhosis.
Portal colopathy has been reported in patients with cirrhosis of the liver. The aim of this study is to evaluate colonic mucosal changes and their clinical significance. Seventy-five cirrhotic patients with anemia and hemoccult-positive stool and 75 control subjects underwent endoscopic examinations of lower gastrointestinal tract. Colonic ectasiae were found to be significantly more common in the 75 cirrhotic patients (80% with hepatitis B or C infection) than control subjects (84% vs 0, p < 0.0001). The lesions in 63 cirrhotic patients were found throughout the entire colon. They included colonic telangiectasiae or angiodysplastic-like lesions in 56 (89%) patients, red spots in 14 (22%), features suggesting mild chronic colitis in 8 (13%), and midrectal colorectal varices in 10 (16%). Pathologic findings in patients with telangiectasiae or angiodysplastic-like lesions showed dilation of vessels (7 of 9 patients) and edema of mucosa (6 of 9 patients). There was no correlation between the severity of cirrhosis, grade of esophageal varices, and the presence of colonic ectasiae. Our observations demonstrate that colonic mucosal changes commonly occur in cirrhotic patients with viral hepatitis. The risk of intermittent hemorrhage from colonic ectasiae should be considered in cirrhotic patients with anemia but without evidence of upper gastrointestinal bleeding. These characteristic lesions may represent a spectrum of portal in hypertensive intestinal vasculopathy.


HGFA Is an Injury-Regulated Systemic Factor that Induces the Transition of Stem Cells into GAlert.
The activation of quiescent stem cells into the cell cycle is a key step in initiating the process of tissue repair. We recently reported that quiescent stem cells can transition into GAlert, a cellular state in which they have an increased functional ability to activate and participate in tissue repair. However, the precise molecular signals that induce GAlert in stem cells have remained elusive. Here, we show that the injury-induced regulation of hepatocyte growth factor (HGF) proteolytic processing via the systemic protease, hepatocyte growth factor activator (HGFA), stimulates GAlert in skeletal muscle stem cells (MuSCs) and fibro-adipogenic progenitors (FAPs). We demonstrate that administering active HGFA to animals is sufficient to induce GAlert in stem cells throughout the body and to significantly accelerate the processes of stem cell activation and tissue repair. Our data suggest that factors that induce GAlert will have broad therapeutic applications for regenerative medicine and wound healing.


Intraductal papillary neoplasm of the bile duct: Radiologic findings in a new disease.
Intraductal papillary neoplasm of the biliary tract (B-IPN) is a scarcely known entity in our daily practice due to its low prevalence. Until its new definition in the fourth edition of the WHO classification of the digestive tract tumors of 2010 the disease was grouped under a heterogeneous and imprecise terminology. In addition, in recent years there has been progress in the knowledge of its etiopathogenesis, its natural history and its findings in image. The purpose of this paper is to review these data underlining the radiological findings of the disease and its differential diagnosis.


Chondrosarcoma simulating malignant atrial myxoma.
A 69-year-old patient underwent removal of a left atrial tumor which was diagnosed clinically and pathologically as atrial myxoma. Fourteen, 18 and 22 months later, distant metastases were discovered. Two of the metastases were removed entirely and one partially. The metastatic tumors were also thought to be of myxomatous origin by light and electron microscopy. Only at autopsy was it demonstrated that the patient had a primary chondrosarcoma of the pelvis giving rise to widespread myxoid metastases to the heart and other sites.


Thrombosis in hematological malignancies: mechanisms and implications.
A B S T R A C T Thrombotic events are a major cause of morbidity and mortality in cancer. While the association of venous thromboembolic events with cancer is well documented, in recent years arterial events (i.e. acute myocardial infarction and ischemic strokes) have also emerged as relatively common complications among cancer patients. In hematological malignancies incorporating a heterogeneous group of diseases, the prediction of thrombosis occurrence and/or recurrence is challenging, due to unique disease characteristics. Furthermore, the treatment of thrombosis in these patients is often complicated because of disease- or therapy-related thrombocytopenia. In addition, patients with hematological cancers are poorly represented in randomized control clinical trials; hence, evidence-based guidelines are limited. This review will discuss the incidence of venous and arterial thrombotic events in common myeloid and lymphoproliferative diseases. Several new mechanisms contributing to cancer- associated thrombosis will be elaborated. The complicated issue of risk assessment and management of venous thrombosis in patients with hematological malignancies will be delineated.


Interventions and Operations after Bariatric Surgery in a Health Plan Research Network Cohort from the PCORnet, the National Patient-Centered Clinical Research Network.
Obesity is a highly prevalent condition with severe clinical burden. Bariatric procedures are an important and expanding treatment option. This study compared short-(30-day composite adverse events) and long-term (intervention/operation, endoscopy, hospitalization, and mortality up to 5 years) safety outcomes associated with three bariatric surgical procedures. This observational cohort study replicated an electronic health record study comparing short- and long-term problems associated with three bariatric surgical procedures between January 1, 2006, and September 30, 2015, within a Health Plan Research Network. Of 95,251 adults, 34,240 (36%) underwent adjustable gastric banding (AGB), 36,206 (38%) Roux-en-Y gastric bypass (RYGB), and 24,805 (26%) sleeve gastrectomy (SG). Median (interquartile range) years of follow-up was 3.3 (1.4-5.0) (AGB), 2.5 (1.0-4.6) (RYGB), and 1.1 (0.5-2.1) (SG). Overall mean (SD) age was 44.2 (11.4) years. The cohort was predominantly female (76%). Thirty-day composite adverse events occurred more frequently following RYGB (3.8%) than AGB (3.1%) and SG (2.8%). Operation/intervention was less likely in SG than in RYGB (adjusted hazard ratio (AHR), 0.87; 95%CI, 0.80-0.96; P=0.003), and more likely in AGB than in RYGB (AHR, 2.10; 95%CI, 2.00-2.21; P<0.001). Hospitalization was less likely after ABG and SG than after RYGB: AGB vs. RYGB, AHR=0.73; 95%CI, 0.71-0.76; P<0.001; SG vs. RYGB, AHR=0.79; 95%CI, 0.76-0.83; P<0.001. Mortality was most likely for RYGB (SG vs. RYGB: AHR, 0.76; 95%CI, 0.64-0.92; P=0.004; AGB vs. RYGB: AHR, 0.49; 95%CI, 0.43-0.56; P=0.001). Interventions, operations, and hospitalizations were more often associated with AGB and RYGB than SG while RYGB had the lowest risk for revision.


Identification of double four-ring units in germanosilicate ITQ-13 zeolite by solid-state NMR spectroscopy.
Well-crystallized Ge-free and Ge-ITQ-13 were successfully obtained by solid state synthesis method. The Ge/Si ratio and the water content that are the two important factors in the synthesis of germanosilicate zeolites were explored for the formation of ITQ-13. The effect of the mineralizing agents (NH4F and NH4Cl) on the ITQ-13 synthesis was investigated as well. The obtained pure silica ITQ-13 and Ge-ITQ-13 were characterized by one- and two-dimensional solid- state NMR techniques. One-dimensional (1D) 19F MAS, 1H→29Si CP/MAS and 19F→29Si CP/MAS NMR spectroscopy evidenced the formation of pure Si-D4R (double four ring) and Ge-D4R units, with the latter being generated by substitution of Si atom from the former units. The detailed configurations of the Ge-D4R units in ITQ-13 was revealed by two-dimensional (2D) 29Si{19F} HETCOR NMR spectroscopy. With the help of theoretical calculations on the 19F and 29Si NMR chemical shifts, six types of D4R units were determined. The formation of the specific D4R unit confirms the structural directing roles of Ge atom and F ions in the formation of the D4R units in zeolite framework. The identification of the SiOSi bonds in the D4R units that connects the layers of ITQ-13 framework provided rationale for the high stability of the ITQ-13 in the degermanation treatment.


Epinephrine, inodilator, or no inotrope in venoarterial extracorporeal membrane oxygenation implantation: a single-center experience.
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can be a rescue therapy for patients in cardiogenic shock or in refractory cardiac arrest. After cannulation, vasoplegia and cardiac depression are frequent. In literature, there are conflicting data on inotropic therapy in these patients. Analysis of a retrospective registry of all patients treated with VA-ECMO in a university hospital center between October 2010 and December 2018 for cardiogenic shock or extracorporeal cardiopulmonary resuscitation (eCPR) with a focus on individual early inotropic therapy. A total of 231 patients (age 58.6 ± 14.3, 29.9% female, 58% eCPR, in-house survival 43.7%) were analyzed. Of these, 41.6% received no inotrope therapy within the first 24 h (survival 47.9%), 29.0% received an inodilator (survival 52.2%), and 29.0% received epinephrine (survival 25.0%). Survival of patients with epinephrine was significantly worse compared to other patient groups when evaluating 30-day survival (p = 0.034/p = 0.005) and cumulative incidence of in-hospital death (p = 0.001). In a multivariate logistic regression analysis, treatment with epinephrine was associated with mortality in the whole cohort (OR 0.38, p = 0.011) as well as after propensity score matching (OR 0.24, p = 0.037). We found no significant differences between patients with inodilator treatment and those without. Early epinephrine therapy within the first 24 h after cannulation for VA-ECMO was associated with poor survival compared to patients with or without any inodilator therapy. Until randomized data are available, epinephrine should be avoided in patients on VA-ECMO.


Activation of TLR2 heterodimers-mediated NF-κB, MAPK, AKT signaling pathways is responsible for Vibrio alginolyticus triggered inflammatory response in vitro.
Vibrio alginolyticus is an important zoonotic marine pathogenic bacterium. Previous studies on the mechanism of innate immune against V. alginolyticus infection have been limited to aquatic animals, however, how V. alginolyticus activates mammalian immune cells has not been fully clarified. Here, ELISA combined RT-qPCR assays were used to detect the secretion and transcription level of pro-inflammatory cytokines and TLRs during V. alginolyticus infection of mice peritoneal macrophages (PMϕs). Western blotting was used to explore the phosphorylation levels of p38, JNK, ERK, AKT and NF-κB protein. Immunofluorescence assay was used to determine the location of NF-κB protein. Inhibition assay was used to study the role of up-regulated TLR in activated signaling pathways and the role of these pathways in the release of pro-inflammatory cytokines. Our data showed that V. alginolyticus can up-regulate the expression levels of IL-1β, IL-6, IL-12 and TNF-α in PMϕs. In addition, V. alginolyticus stimulation activated the phosphorylation of p38, JNK and ERK were TLR2 heterodimers-dependent, whereas inhibitors of SB203580 (p38), SCH772984 (ERK) and SP600125 (JNK) significantly reduced IL-1β, IL-6, IL-12 and TNF-α production. We further revealed that V. alginolyticus activated the signaling pathways of AKT via TLR2 heterodimers. The inhibitor of MK-2206 2HCl (AKT) negatively regulated the IL-1β, IL-6 and TNF-α release levels. Moreover, V. alginolyticus infection of PMϕs resulted in TLR2 heterodimers-mediated activation of NF-κB and induced translocation of phosphorylated NF-κB protein from the cytoplasm into the nucleus via IκBα degradation. V. alginolyticus induced IL-1β, IL-6, IL-12 and TNF-α release were blocked by the specific NF-κB inhibitor, BAY 11-7082. Taken together, our results suggested that activation of the TLR2 heterodimers-mediated downstream signaling pathways NF-κB, MAPK and AKT is responsible for inflammatory response during Vibrio alginolyticus infection in vitro.


Magnetic resonance velocity imaging derived pressure differential using control volume analysis.
Diagnosis and treatment of hydrocephalus is hindered by a lack of systemic understanding of the interrelationships between pressures and flow of cerebrospinal fluid in the brain. Control volume analysis provides a fluid physics approach to quantify and relate pressure and flow information. The objective of this study was to use control volume analysis and magnetic resonance velocity imaging to non-invasively estimate pressure differentials in vitro. A flow phantom was constructed and water was the experimental fluid. The phantom was connected to a high-resolution differential pressure sensor and a computer controlled pump producing sinusoidal flow. Magnetic resonance velocity measurements were taken and subsequently analyzed to derive pressure differential waveforms using momentum conservation principles. Independent sensor measurements were obtained for comparison. Using magnetic resonance data the momentum balance in the phantom was computed. The measured differential pressure force had amplitude of 14.4 dynes (pressure gradient amplitude 0.30 Pa/cm). A 12.5% normalized root mean square deviation between derived and directly measured pressure differential was obtained. These experiments demonstrate one example of the potential utility of control volume analysis and the concepts involved in its application. This study validates a non-invasive measurement technique for relating velocity measurements to pressure differential. These methods may be applied to clinical measurements to estimate pressure differentials in vivo which could not be obtained with current clinical sensors.


Perforated jejunal diverticulitis with extensive diverticulosis: A case report.
Jejunal diverticulitis is a rare condition that almost occurs in the elderly. An extensive diverticulosis associated is exceptional and can make the treatment more challenging.


The determination of relationship between "excision repair cross-complementing group 1" (ERCC1) gene T19007C and C8092A single nucleotide polymorphisms and clinicopathological parameters in non-small cell lung cancer.
DNA repair plays a key role in prevention of carcinogenesis and one of the most important DNA repair mechanisms is nucleotide excision repair (NER) pathway. This pathway includes a number of genes such as excision repair cross-complementing group 1 (ERCC1) gene which are responsible for the 5' incision of damaged DNA. A reduced DNA repair capacity associated with ERCC1 mRNA level has been observed in lung carcinogenesis. Two single nucleotide polymorphisms (SNPs) in ERCC1 gene, T19007C (rs11615) and C8092A (rs3212986), reportedly predict to affect the mRNA of ERCC1 in non-small cell lung cancer (NSCLC). To examine the role of two common SNPs in ERCC1 gene further, we conducted this study where 80 cases histopatologically diagnosed as NSCLC were genotyped. Genomic DNA was extracted from formalin-fixed, paraffin embedded tissues and two SNPs were analyzed using real-time PCR. The distributions of TT, TC, and CC genotypes of the T19007C SNP were 40, 44 and 16%, respectively. Significantly increased frequency of the patients carrying at least one 19007C allele was observed in early stage compared to advanced stage (P=0.002). And also, the frequency of TC and CC genotypes significantly increased in younger patients compared to older patients (P=0.035). Regarding C8092A SNP, the distribution of CC, CA, and AA genotypes was 38, 51 and 11%, respectively. There was no significant difference in the genotype distribution between C8092A SNP and clinicopathological parameters. This study indicated that harboring at least one 19007C allele may have protective effect in NSCLC.


Alpelisib-induced hyperglycemia in older patients with breast Cancer: Qualitative findings.
The PIK3 kinase inhibitor, alpelisib, is a new breast cancer drug that can cause hyperglycemia, which can be especially severe in older patients. Yet, to our knowledge, no prior studies have sought to understand what older patients experience with alpelisib-induced hyperglycemia. The medical records of patients who were 65 years of age or older at the initiation of alpelisib and who developed hyperglycemia were reviewed in detail; direct verbiage on hyperglycemia were extracted and reviewed with rigorous qualitative methods. Thirty-four women with a median age of 72 (range: 65, 85) are the subject of this report; twelve had been started on insulin, four had been hospitalized for hyperglycemia, and eleven appeared to stop alpelisib because of hyperglycemia. Qualitative analyses revealed two themes. The first was patient burden, which emanated from patients' having to self-monitor glucose levels ("Monitors blood glucose (BG) 4 times daily"); taking extra medications ("Taking Jardiance 10 mg daily and Pioglitazone 15 mg daily"); frequent changes in insulin dosing ("Her insulin… was then increased…."); and frequent changes in dosing of alpelisib to help control the hyperglycemia ("Instructed to hold Piqray …."), and which also emanated from greater engagement with the healthcare system ("She was hospitalized for hyperglycemia"). The second theme focused on symptomatology and how patients suffered from hyperglycemia ("She presents to the emergency department with pre-syncope and vertigo"). Oncologists should assess older patients for the requisite abilities and resources for managing alpelisib-induced hyperglycemia in the event it occurs.


Difference in pyruvate kinase regulation among three groups of yeasts.
Yeast pyruvate kinase (ATP : pyruvate 2-O-phosphotransferase EC 188.8.131.52) was classified into three groups based on the interaction with fructose-1,6-bisphosphate. The pyruvate kinases of Saccharomyces cerevisiae and Saccharomyces carlsbergensis were activated by fructose 1,6-bisphosphate in the concentration range tested (up to 10 mM) of the substrate, phosphoenolpyruvate; the enzymes of "fermentative Candida" (Candida tropicalis and Candida utilis) were affected by fructose 1,6-biphosphate only when the substrate concentration was below 2 mM. Although the pyruvate kinase of Candida lipolytica (a yeast belonging to "oxidative Candida") was also affected by fructose 1,6-bisphosphate, the degree of the activation was extremely small as compared with the above four yeasts. The pyruvate kinase of C. tropicalis was inhibited by ATP more strongly in the absence of fructose 1,6-bisphosphate than its presence. In the case of the C. lipolytica enzyme, however, the enzyme was inhibited to a lesser extent by ATP, and fructose 1,6-bisphosphate did not reverse the inhibitory effect of ATP. Time course changes of the enzyme levels in the yeasts grown on glucose and on ethanol indicate that the pyruvate kinases of S. cerevisiae and C. tropicalis can be controlled both by an allosteric mechanism and by changes in the enzyme concentration, although a marked difference was observed in the susceptibility to the allosteric effect by fructose 1,6-biphosphate between these fermentative yeasts. On the other hand, that of C. lipolytica would be controlled only by the latter mechanism.


Prevalence of HPV infection among Thai schoolgirls in the north-eastern provinces in 2018: implications for HPV immunization policy.
The aim of this study was to determine the prevalence of high-risk (HR) and vaccine-type human papillomavirus (HPV) infection among Thai schoolgirls who were not included in the national HPV immunization program. Cross-sectional surveys were conducted among grade 10 (15-16 years old) and grade 12 (17-18 years old) schoolgirls in two provinces of Thailand. Urine samples were collected using the Colli-PeeⓇ device from November 2018 to February 2019. The samples were initially tested using CobasⓇ 4800. Subsequently, all Cobas-positive samples and 1:1 matched Cobas-negative samples were tested by AnyplexⓇ assay. Prevalences of any HPV, any HR HPV, vaccine-type HPV, and individual HR HPV types were estimated by school grade. Prevalences of any HPV and any HR HPV were 11.6% and 8.6% for grade 10, and 18.5% and 12.4% for grade 12 schoolgirls, respectively. Prevalences of bivalent vaccine-type HPV infection in grades 10 and 12 were 3.4% and 4.5%, respectively. Prevalences of quadrivalent and nonavalent vaccine-type HPV infections were 4.0%/6.6% and 6.4%/10.4% in grades 10 and 12, respectively. HPV16 was the most common type detected, followed by HPV58, 51, and 52. Circulating HR HPV types were similar between the school grades. A substantial burden of HR HPV infections was found among unvaccinated high school girls in Thailand.


End-of-life care and advance care planning for outpatients with inoperable aortic aneurysms.
A significant proportion of patients with abdominal and thoracic aortic aneurysms (AA) do not proceed to intervention after reaching treatment threshold diameter due to a combination of poor cardiovascular reserve, frailty, and aortic morphology. This patient cohort has a high mortality; however, until this study, there exist no studies on the end-of-life care conservatively managed patients receive. This is a retrospective multicenter cohort study of 220 conservatively managed patients with AA referred to Leeds Vascular Institute (UK) and Maastricht University Medical Centre (the Netherlands) for intervention between 2017 and 2021. Demographic details, mortality, cause of death, advance care planning and palliative care outcomes were analysed to examine predictors of palliative care referral and efficacy of palliative care consultation. A total of 1506 patients with AA were seen over this time period, giving a nonintervention rate of 15%. There was a 3-year mortality rate of 55%, a median survival of 364 days, and rupture was the reported cause of death in 18% of the decedents. Median follow-up was 34 months. Only 8% of all patients and 16% of decedents received a palliative care consultation, which took place a median of 3.5 days before death. Patients >81 years of age were more likely to have advance care planning. Only 5% and 23% of conservatively managed patients had documentation of preferred place of death and care priorities respectively. Patients with a palliative care consultation were more likely to have these services in place. Only a small proportion of conservatively treated patients had advance care planning and this was far below international guidelines on end-of-life care for adults, which recommends it for each of these patients. Pathways and guidance should be implemented to ensure patients not offered AA intervention receive end-of-life care and advance care planning.


Diagnosis and treatment of obturator hernia: retrospective analysis of 86 clinical cases at a single institution.
To explore the clinical characteristics, diagnosis and treatment of obturator hernia. Eighty-six patients who were diagnosed as obturator hernia by abdominal CT in the Department of Gastrointestinal Surgery of our hospital between 2009 and 2019 were enrolled in this study. Patient characteristics, surgical method, postoperative complications and mortalities were retrospectively reviewed. Thirty days mortality rate of 5.5% and 46.1% were observed in surgery group and non-surgery group, respectively. Surgery was performed as an emergency procedure in 59 cases and elective procedure in 14 cases depending on different hernia contents, intestinal necrosis and signs of peritonitis. In the emergency surgery group, segmental intestinal resection with anastomosis was performed in 24 patients (24/59, 40.7%). There were 4 deaths (4/59, 6.8%) in this group, all of which occurred in patients undergoing SI resections. In contrast, no bowel resection, postoperative complications, or death occurred in the elective surgery group. 3-year recurrence rates of 5.1% (3/59) and 7.1% (1/14) were observed in the emergency surgery and the elective surgery group, respectively. CT examination plays an important role in improving the diagnostic rate of obturator hernia. Timely surgical treatment is the key to improve the efficacy of obturator hernia and prevent the deterioration of the condition. In addition, intestinal resection and postoperative complications may be the important factors leading to postoperative death.


The advantages and disadvantages of being polyploid.
Polyploids - organisms that have multiple sets of chromosomes - are common in certain plant and animal taxa, and can be surprisingly stable. The evidence that has emerged from genome analyses also indicates that many other eukaryotic genomes have a polyploid ancestry, suggesting that both humans and most other eukaryotes have either benefited from or endured polyploidy. Studies of polyploids soon after their formation have revealed genetic and epigenetic interactions between redundant genes. These interactions can be related to the phenotypes and evolutionary fates of polyploids. Here, I consider the advantages and challenges of polyploidy, and its evolutionary potential.


Complexity of the thoracic spine pedicle anatomy.
Transpedicular screw fixation provides rigid stabilization of the thoracolumbar spine. For accurate insertion of screws into the pedicles and to avoid pedicle cortex perforations, more precise knowledge of the anatomy of the pedicles is necessary. This study was designed to visualize graphically the surface anatomy and internal architecture of the pedicles of the thoracic spine. Fifteen vertebrae distributed equally among the upper, middle, and lower thoracic regions were used. For the purpose of mapping surface anatomy, each pedicle was cleaned, spray-painted white, and marked with more than 100 fine points. Using an optoelectronic digitizer, three-dimensional coordinates of the marked points and three additional points, representing a coordinate system, were digitized. A solid modeling computer program was used to create three-dimensional surface images of the pedicle. To obtain cross-sectional information, each pedicle was sectioned with a thin diamond-blade saw to obtain four slices, 1 mm in thickness and 0.5 mm apart. The pedicle slices were X-rayed and projected onto a digitizer. The internal and external contours were digitized and converted into graphs by a computer. The pedicles exhibited significant variability in their shape and orientation, not only from region to region within the thoracic spine, but also within the same region and even within the same pedicle. These variations are extremely significant in light of current techniques utilized in transpedicular screw fixation in the thoracic spine. Information documenting the three-dimensional complexity of pedicle anatomy should be valuable for surgeons and investigators interested in spinal instrumentation.


3D Amide Proton Transfer-Weighted Imaging for Grading Glioma and Correlating IDH Mutation Status: Added Value to 3D Pseudocontinuous Arterial Spin Labelling Perfusion.
The goal of this study was to evaluate the diagnostic performance of 3D amide proton transfer-weighted (3D-APTW) imaging and 3D pseudocontinuous arterial spin labelling (3D-pCASL) alone and in combination in grading gliomas (low-grade glioma (LGG) vs. high-grade glioma (HGG)) and correlating isocitrate dehydrogenase (IDH) mutation status. Preoperatively, 81 patients with pathologically confirmed gliomas underwent 3.0-T magnetic resonance imaging (MRI) examinations. The APTW, relative APTW (rAPTW), cerebral blood flow (CBF), and relative CBF (rCBF) values were calculated to evaluate the solid components of the tumours. The MRI parameters were compared in the classification of gliomas by independent- and paired-samples t tests. A receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to assess the diagnostic performance of each parameter and the combination of the rAPTW and rCBF values. Patients with HGG showed significantly higher APTW, rAPTW, CBF, and rCBF values than those with LGG (all p < 0.001). In the ROC curve analysis, the AUC of rAPTW was the highest at 0.90. By adding the rAPTW signal to the rCBF values, the diagnostic ability of the combined parameters improved from 0.90 to 0.96. The rAPTW value yielded the highest AUC (0.92) in correlating the IDH mutation status, and the diagnostic ability improved to 0.96 by adding it to the rCBF value. 3D-APTW imaging combined with 3D-pCASL imaging may be used to aid assessment of grading glioma and IDH mutation status.


Recurrence of spontaneous pneumothorax six years after VATS pleurectomy: evidence for formation of neopleura.
Primary Spontaneous Pneumothorax (PSP) is considered an absolute and definitive contraindication for scuba diving and professional flying, unless bilateral surgical pleurectomy is performed. Only then is there a sufficiently low risk of recurrence to allow a waiver for flying and/or diving. A young fit male patient who suffered a PSP 6 years ago, and underwent an uncomplicated videoscopic surgical pleurectomy, presented with a complete collapse of the lung on the initial PSP side. Microscopic examination of biopsies showed a slightly inflamed tissue but otherwise normal mesothelial cells, compatible with newly formed pleura. Even with pleurectomy, in this patient, residual mesothelial cells seem to have had the capacity to create a completely new pleura and pleural space. The most appropriate surgical technique for prevention of PSP may still be debated.


Contrast-enhanced ultrasound of the liver and kidney.
The clinical use of noncardiac contrast-enhanced ultrasound scan (CEUS) has been steadily gaining momentum. CEUS is a reliable and safe technique with a diverse array of applications. This article reviews the current and potential future clinical applications of CEUS. Emphasis will be placed on evaluating focal lesions with the liver and kidney. Contrast agent composition and mechanism are also briefly reviewed.


Probing TGF-β1-induced cytoskeletal rearrangement by fluorescent-labeled silica nanoparticle uptake assay.
Cytoskeletal proteins are essential in maintaining cell morphology, proliferation, and viability as well as internalizing molecules in phagocytic and non-phagocytic cells. Orderly aligned cytoskeletons are disturbed by a range of biological processes, such as the epithelial-mesenchymal transition, which is observed in cancer metastasis. Although many biological methods have been developed to detect cytoskeletal rearrangement, simple and quantitative in vitro approaches are still in great demand. Herein, we applied a flow cytometry-based nanoparticle uptake assay to measure the degree of cytoskeletal rearrangement induced by transforming growth factor β1 (TGF-β1). For the assay, silica nanoparticles, selected for their high biocompatibility, were fluorescent-labeled to facilitate quantification with flow cytometry. Human keratinocyte HaCaT cells were treated with different concentrations of TGF-β1 and then exposed to FITC-labeled silica nanoparticles. Increasing concentrations of TGF-β1 induced gradual changes in cytoskeletal rearrangement, as confirmed by conventional assays. The level of nanoparticle uptake increased by TGF-β1 treatment in a dose-dependent manner, indicating that our nanoparticle uptake assay can be used as a quick and non-destructive approach to measure cytoskeletal rearrangement.


Signal transduction by CD58: the transmembrane isoform transmits signals outside lipid rafts independently of the GPI-anchored isoform.
The adhesion molecule CD58 is natively expressed in both a glycosylphosphatidylinositol (GPI)-anchored form and a transmembrane form. We previously demonstrated that the two isoforms of CD58 are differentially distributed in the cell membrane. The GPI-linked form resides in lipid rafts while the transmembrane form resides outside lipid rafts. Following cross-linking a fraction of transmembrane CD58 redistributes to lipid rafts. It has also been demonstrated that ligand binding to CD58 induces biological functions such as cytokine production and immunoglobulin isotype switching, indicating that cell-cell interactions result in CD58-mediated signal transduction. However, the signaling pathways involved in these activation processes are poorly defined. Here we show for the first time that cross-linking of CD58 induces protein tyrosine phosphorylation of BLNK, Syk and PLCgamma, and activation of ERK and Akt/PKB. In addition, we studied how these signaling events relate to the distinct membrane localization of the two isoforms of CD58. We demonstrate that cross-linking of CD58 triggers signaling that is predominantly associated with transmembrane CD58 in nonraft microdomains. Moreover, signaling through transmembrane CD58 does not depend on coexpression of the GPI-linked isoform. Thus, despite the residence of its GPI-anchored isoform in lipid rafts and the translocation of a fraction of its transmembrane isoform to lipid rafts, CD58 signaling is triggered by the transmembrane isoform outside lipid rafts. These findings corroborate signaling outside lipid rafts, as opposed to the established notion that rafts function as essential platforms for signaling.


Verification of hotspots of genetic diversity in Korean population of Grateloupia asiatica and G. jejuensis (Rhodophyta) show low genetic diversity and similar geographic distribution.
Understanding the genetic diversity and distribution patterns of seaweeds species is crucial for evaluating key regions of high genetic diversity. Identifying hotspots of high intraspecific diversity is an important step for developing conservation strategies. Grateloupia is a diverse genus of Rhodophyta, many of which are resource of numerous useful bioactive compounds; therefore, the genus is valuable target for conservation. The aim of this study is to examine the genetic diversity and population structure of two Grateloupia species, Grateloupia asiatica and Grateloupia jejuensis, with the understanding of the phylogeography of the Korean genetic diversity hotspot for two species. Plastid rbcL gene sequences of 134 specimens of G. asiatica and 112 specimens of G. jejuensis collected from the Korean coast were analyzed. We evaluated the number of haplotypes, genetic diversity (haplotype and nucleotide diversity), and haplotype networks of two species. Historical demographic was inferred by calculating neutrality tests and genetic differentiation was estimated using the fixation index, FST. Our results show that both species are generally similar in geographical distribution patterns, that is, relatively homogeneous with few haplotypes derived from the most frequent haplotype. The east coast of Korea is identified as a 'hotspot' with the highest genetic diversity for both species, whereas Jeju Island is identified as a 'cold spot' with the lowest genetic diversity for G. jejuensis. Analyses across most distribution ranges of the two species in Korea reveal low genetic and haplotype diversities, which could indicate that these two Grateloupia species have either experienced a historical lack of diversity or a recent reduction in diversity due to high gene flow. The low genetic diversity values found in the present study raise considerable concern about the conservation status of these two Grateloupia species and highlight the need to locate further hotspots of genetic diversity to strengthen their resilience against further decline.


2- and 3-substituted imidazo[1,2-a]pyrazines as inhibitors of bacterial type IV secretion.
A novel series of 8-amino imidazo[1,2-a]pyrazine derivatives has been developed as inhibitors of the VirB11 ATPase HP0525, a key component of the bacterial type IV secretion system. A flexible synthetic route to both 2- and 3-aryl substituted regioisomers has been developed. The resulting series of imidazo[1,2-a]pyrazines has been used to probe the structure-activity relationships of these inhibitors, which show potential as antibacterial agents.


2,7-functionalized indoles as receptors for anions.
A series of 2,7-functionalized indoles have been synthesized with appended amide and/or urea or thiourea groups. Anion complexation studies show a marked difference in the mode of interaction of carboxylates with indole-ureas vs indole-amides.


Footedness and Postural Asymmetry in Amateur Dressage Riders, Riding in Medium Trot on a Dressage Simulator.
This study explored the relationship between footedness and postural asymmetry in equestrian riders. 28 female riders completed the Waterloo Footedness Questionnaire- Revised (WFQ-R), giving a score for footedness. They then took part in a test on a riding simulator where measures of saddle force, stirrup force, and degree of lateral tilt of the pelvic, trunk, and shoulder segments were taken over a period of 20 seconds in trot. Symmetry indices were calculated for stirrup force and saddle force. There were no significant correlations between WFQ-R score and any of the measures of postural symmetry. Only a very small number (n=3) participants showed a marked footedness, with the majority of the sample being classed as 'mixed footed' based on test scores. This, coupled with data loss for some participants in each of the parameters, means direct comparison of footedness groups was difficult. However, the variation of asymmetry in the mixed footed group supports the idea that footedness does not have a significant impact on the rider's posture. There was a correlation between trunk lean and stirrup force symmetry index (r=0.537, P=0.021) showing the trunk leaned towards the side of higher stirrup force. There was a significant negative correlation between pelvic obliquity and shoulder tilt (r= -0.481, P=0.023) with 59% of the sample showing pelvic obliquity and shoulder tilt in opposite directions. The findings indicate that there is little effect of footedness on postural asymmetries in the rider. Research should now consider other causal factors to support riders to become more symmetrical.


Overexpression of FTL1/DDF1, an AP2 transcription factor, enhances tolerance to cold, drought, and heat stresses in Arabidopsis thaliana.
Freezing temperatures control where and when plants can grow, and negatively influence crop quality and productivity. To identify key regulatory genes involved in cold adaptation, we screened activation-tagged Arabidopsis lines for mutants with greater freezing tolerance. One mutant, freezing tolerant line1 (ftl1-1D), manifested enhanced tolerance along with dwarfism and delayed flowering. This was caused by activation of DWARF AND DELAYED FLOWERING 1 (DDF1), a gene previously described as a regulatory component in salinity signaling. The induced gene encoded an AP2 transcription factor of the CBF/DREB1 subfamily. In addition to conferring tolerance to low temperatures and salt stress, ftl1-1D/ddf1 improved tolerance to drought and heat. Real-time PCR indicated that FTL1/DDF1 was up-regulated by those four types of stresses in wild-type Arabidopsis. Its increased expression in the mutant induced various stress-responsive genes under normal growing conditions, resulting in improved tolerances. However, phenotypes shown in the ftl1-1D/ddf1 were restored by treatment with exogenous gibberellin (GA₃), indicating the involvement of a GA pathway in FTL1/DDF1-mediated tolerance. Therefore, we conclude that FTL1/DDF1 plays a role in regulating responses to several abiotic stresses, perhaps via cross-talk in the pathways.


Structural and catalytic characteristics of Escherichia coli adenylate kinase.
The adk gene encoding adenylate kinase in Escherichia coli was cloned in pBR322. Adenylate kinase represented about 4% of total proteins in extracts of cells containing the pBR322:adk plasmid. This allowed preparation of more than 90% pure enzyme in a single-step purification procedure. Amino acid analysis, high performance liquid chromatography separation of trypsin digests, sequence analysis of most peptides, and determination of the N-terminal sequence of the whole protein confirmed the primary structure of E. coli adenylate kinase predicted from the nucleotide sequence of the adk gene (Brune, M., Schumann, R., and Wittinghofer, F. (1985) Nucleic Acids Res. 13, 7139-7151). 2-Nitro-5-thiocyanatobenzoic acid reacted with the single cysteine residue of E. coli adenylate kinase. The cyanylated protein was cleaved upon exposure to alkaline pH, yielding two peptides corresponding to residues 1-76 and 77-214, respectively. A mixture of purified peptides tended to reassociate, recovering both catalytic activity and binding properties for adenine nucleotides. E. coli adenylate kinase has a broader specificity for nucleoside monophosphates than does the mammalian enzyme. In addition to 2'-dAMP, other nucleoside monophosphates such as 3'-dAMP, adenine-9-beta-D-arabinofuranoside 5'-monophosphate, and 7-deazaadenosine (tubercidine) 5'-monophosphate were able to replace AMP as substrate.


An intelligent probe with dual-emission in water and oil for lipid droplet specific imaging in human fibrocalcific aortic valvular leaflet.
Lipid droplets (LDs) have been regarded as potential marker for study the pathologic processes and diagnosis of valvular heart disease. While conventional imaging strategy fail to precisely locate LDs in pathological tissues. Herein, a LDs specific probe ECPID with special feature of single-excitation but dual-emission in oil (520 nm) and water (628 nm) was prepared for LDs imaging. ECPID exhibited good biocompatibility, great performance in intracellular and tissular LDs imaging, which would help to reveal the pathologic process of human fibrocalcific aortic valvular leaflet. Our work offers a novel approach for accurate imaging LDs in situ and paves a way to study the pathologic processes of valvular disease.


Ultrasonically assisted surface modified CeO2 nanospindle catalysts for conversion of CO2 and methanol to DMC.
This study developed a facile and effective approach to engineer the surface properties of cerium oxide (CeO2) nanospindle catalysts for the direct synthesis of dimethyl carbonate (DMC) from CO2 and methanol. CeO2 nanospindles were first prepared by a simple precipitation method followed by wet chemical redox etching with sodium borohydride (NaBH4) under high intensity ultrasonication (ultrasonic horn, 20 kHz, 150 W/cm2). The ultrasonically assisted surface modification of the CeO2 nanospindles in NaBH4 led to particle collisions and surface reduction that resulted in an increase in the number of surface-active sites of exposed Ce3+ and oxygen vacancies. The surface modified CeO2 nanospindles showed an improvement of catalytic activity for DMC formation, yielding 17.90 mmol·gcat-1 with 100 % DMC selectivity. This study offers a simple and effective method to modify a CeO2 surface, and it can further be applied for other chemical activities.


A case of invasive lobular carcinoma of the breast first manifesting with duodenal obstruction.
Lobular carcinoma of the breast presents with various clinical manifestations. Lobular carcinoma comprises about one fifth of cases of ductal carcinoma. Intestinal metastasis is dominant in cases of lobular carcinoma. Without a prior diagnosis of lobular carcinoma of the breast, the diagnosis of intestinal metastasis from breast cancer is difficult. A 52-year-old women underwent duodenogastrectomy for duodenal cancer. About 18 months later, she underwent mastectomy for lobular carcinoma of the breast. The duodenal cancer consisted mainly of malignant cells invading the submucosa that were identical to those in the breast. Immunohistochemical assays for estrogen receptor also confirmed breast cancer metastasis. Duodenal obstruction was the first sign of isolated metastatic lobular carcinoma of the breast in this case. The characteristic metastatic pattern of lobular carcinoma, which differs from that of ductal carcinoma, should be kept in mind to ensue proper diagnosis. Preceding breast surgery for lobular carcinoma should prompt investigation based on the typical metastatic pattern.


Timed study of experimental primary neural induction.
Experimental primary neural induction was studied by transmission electron microscopy and compared with normal primary neural induction studies. A change was observed in the ectoderm cytoplasm and the ribosomes formed polysomes in the same way as previously described in normal induction.


The efficacy of cariprazine on cognition: a post hoc analysis from phase II/III clinical trials in bipolar mania, bipolar depression, and schizophrenia.
To investigate the effect of cariprazine on cognitive symptom change across bipolar I disorder and schizophrenia. Post hoc analyses of 3- to 8-week pivotal studies in bipolar I depression and mania were conducted; one schizophrenia trial including the Cognitive Drug Research System attention battery was also analyzed. Outcomes of interest: Montgomery-Åsberg Depression Rating Scale [MADRS], Functioning Assessment Short Test [FAST], Positive and Negative Syndrome Scale [PANSS]). LSMDs in change from baseline to end of study were reported in the overall intent-to-treat population and in patient subsets with specified levels of baseline cognitive symptoms or performance. In patients with bipolar depression and at least mild cognitive symptoms, LSMDs were statistically significant for cariprazine vs placebo on MADRS item 6 (3 studies; 1.5 mg=-0.5 [P<.001]; 3 mg/d=-0.2 [P<.05]) and on the FAST Cognitive subscale (1 study; 1.5 mg/d=-1.4; P=.0039). In patients with bipolar mania and at least mild cognitive symptoms, the LSMD in PANSS Cognitive subscale score was statistically significant for cariprazine vs placebo (3 studies; -2.1; P=.001). In patients with schizophrenia and high cognitive impairment, improvement in power of attention was observed for cariprazine 3 mg/d vs placebo (P=.0080), but not for cariprazine 6 mg/d; improvement in continuity of attention was observed for cariprazine 3 mg/d (P=.0012) and 6 mg/d (P=.0073). These post hoc analyses provide preliminary evidence of greater improvements for cariprazine vs placebo across cognitive measures in patients with bipolar I depression and mania, and schizophrenia, suggesting potential benefits for cariprazine in treating cognitive symptoms.


Exosomal miR-146a-5p derived from human umbilical cord mesenchymal stem cells can alleviate antiphospholipid antibody-induced trophoblast injury and placental dysfunction by regulating the TRAF6/NF-κB axis.
Exosomes originating from human umbilical cord mesenchymal stem cells (hucMSC-exos) have become a novel strategy for treating various diseases owing to their ability to regulate intercellular signal communication. However, the potential of hucMSC-exos to improve placental injury in obstetric antiphospholipid syndrome and its underlying mechanism remain unclear. Our objective was to explore the potential application of hucMSC-exos in the treatment of obstetric antiphospholipid syndrome and elucidate its underlying mechanism. In our study, hucMSC-exos ameliorated the functional impairment of trophoblasts caused by antiphospholipid antibodies in vitro and attenuated placental dysfunction in mice with obstetric antiphospholipid syndrome by delivering miR-146a-5p. Exosomal miR-146a-5p suppressed the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibited the activation of NF-κB signaling, leading to the down-regulation of IL-1β and IL-18 to rescue inflammation and modulation of Cleaved-CASP3, BAX, and BCL2 to inhibit apoptosis in HTR8/SVneo cells and mice placenta. This study identified the potential molecular basis of how hucMSC-exos improved antiphospholipid antibody-induced placental injury and highlighted the functional importance of the miR-146a-5p/TRAF6 axis in the progression of obstetric antiphospholipid syndrome. More importantly, this study provided a fresh outlook on the promising use of hucMSC-exos as a novel and effective treatment approach in obstetric antiphospholipid syndrome.


Let's hear about nursing practice.
A few weeks ago, I had the good fortune to attend the eighth International Council of Nurses conference dedicated to advanced nursing practice.


[Prolactinoma: from quest of pregnancy to delivery].
Prolactinoma is the most frequent hormone-secreting pituitary tumor (100 for million patients) and a major cause of both female and male reproductive function disorders. Physician, gynecologist, urologist and sexologist can face this situation during their career. As part of the fertility restoration, treatment gives very satisfactory results. With adequate management, most women are expected to achieve successful pregnancies. The natural history of these tumors during pregnancy depends on their size with a risk of a clinically relevant estimate between 5 to 30 %. Their management is complex, requiring finding balance between effects of pregnancy on tumor growth and potential risks of overtreatment on fetal development. The aim of this study is to discuss the management of prolactinoma on woman before, during and after pregnancy, and to evaluate the medical and surgical alternatives regarding the actual literature.


Visualization and GPU-accelerated simulation of medical ultrasound from CT images.
We present a fast GPU-based method for simulation of ultrasound images from volumetric CT scans and their visualization. The method uses a ray-based model of the ultrasound to generate view-dependent ultrasonic effects such as occlusions, large-scale reflections and attenuation combined with speckle patterns derived from pre-processing the CT image using a wave-based model of ultrasound propagation in soft tissue. The main applications of the method are ultrasound training and registration of ultrasound and CT images.


Practical Approach to Hyperandrogenism in Women.
The approach to hyperandrogenism in women varies depending on the woman's age and severity of symptoms. Once tumorous hyperandrogenism is excluded, the most common cause is PCOS. Hirsutism is the most common presenting symptom. The woman's concern about her symptoms plays an important role in the management of disease. Although measurement of testosterone is useful in identifying an underlying cause, care must be taken when interpreting the less accurate assays that are available commercially. Surgical resection is curative in tumorous etiologies, whereas medical management is the mainstay for non-tumorous causes.


Effects of surgery on the relationship between subglottic pressure and fundamental frequency in vocal fold dynamics in patients with benign laryngeal diseases.
Subglottic pressure (Ps) and fundamental frequency (F0) play important roles in governing vocal fold (VF) dynamics. Theoretical description, model simulation, excised larynx and animal models have been used in previous studies, yet clinically applicable measurements are still lacking. This study aimed to evaluate the effects of surgery for benign laryngeal lesions by investigating the relationship between F0 and Ps. Patients with benign laryngeal lesions who underwent phonosurgery were prospectively recruited. Participants were instructed to sustain voicing the vowel /o/ at three incremental frequencies four semitones apart in the modal register (F01, F02, F03). F0 was estimated by VF vibration on the accelerometer. Ps change was achieved and measured using the airflow interruption method. Thirteen patients with a mean age (SD) of 43.5 (12.4) years were included. The change in F0 per unit change of Ps, which is the slope (Hz/kPa) of the regression line of the frequency-pressure data pairs, decreased as the tension of the VF increased. The slopes significantly increased after the operation for F01 and F02 (36.43 ± 14.68 preoperatively, 53.91 ± 30.71 postoperatively, p = 0.011 and 26.02 ± 10.71; 34.85 ± 17.92, p = 0.046, respectively). In addition, there was a significant decrease in phonation threshold pressure and improvements in the grade, roughness, breathiness, asthenia, strain scale, and the voice handicap inventory-10. The relationship between F0 and Ps may serve as an objective assessment of the outcomes in the treatment of benign laryngeal diseases with clinical relevance.


Red mud with other waste materials as artificial soil substitute and its effect on Sinapis alba.
Despite efforts to utilise bauxite residue, the amount of red mud stored in reservoirs is increasing. This paper aims to evaluate the potential of red mud and other sludge waste types as a soil substitute by monitoring plant development. Pot experiments were carried out testing two types of mixtures: dredging sludge from Lake Balaton mixed with garden soil and the sewage sludge and soil blend. These were then treated with red mud (15 and 30% w/w). The plants were under-, while the roots were more developed in the sewage sludge mix than the dredging sludge blend and the control soil. In the sewage amendment, the phosphorous content increased while the calcium content was lower than in the other soil types and the optimum. The metals uptake of the plants was a factor of the red mud quantity. Lead, nickel, titanium and silicon had elevated concentrations parallel to higher red mud content, but only the nickel exceeded the threshold of the Hungarian legislation. Silicon and titanium were beneficial for plant growth, compensating for the potentially toxic effects of lead and nickel. Results suggest that the red mud in a mixture with either sewage sludge or dredging sludge can act as catalysts for the growth rate of test plants, allowing their utilisation as secondary raw materials.


The use of procalcitonin in the diagnosis of late-onset infection in neonatal intensive care unit patients.
We evaluated the semi-quantitative procalcitonin level for diagnosing late-onset infections in 176 neonates. Using a cut-off level of 0.5 ng/ml, the sensitivity was 84.4%+/-0.19, specificity was 93.9%+/-0.04, positive predictive value was 82.6%+/-0.1, and negative predictive value was 94.6%+/-0.04. Procalcitonin could be a useful marker of late-onset infection in neonates.


Dimethoate blocks pubertal differentiation of Leydig cells in rats.
Dimethoate is an organophosphate pesticide. It is widely used in agriculture. However, whether it blocks pubertal development of Leydig cells remains unknown. In the current study, we exposed male Sprague Dawley rats with 7.5 and 15 mg kg-1 dimethoate from postnatal day 35-56. We also exposed Leydig cells isolated from 35-day-old rats for 3 h. Dimethoate reduced serum testosterone levels at 7.5 and 15 mg kg-1 but increased serum luteinizing hormone and follicle stimulating hormone levels at 15 mg kg-1. Dimethoate did not influence Leydig cell number but reduced Leydig cell size and down-regulated Star, Cyp11a1, and Hsd3b1 in Leydig cells as well as their protein expression. Dimethoate inhibited basal androgen output in a dose-dependent manner with the inhibition starting at 0.05 μM. It significantly inhibited luteinizing hormone and 8Br-cAMP stimulated androgen outputs at 50 μM. It significantly inhibited 22R-hydroxycholesterol and progesterone-mediated androgen outputs at 50 μM. Further study demonstrated that dimethoate also down-regulated the expression of Star, Cyp11a1, and Hsd3b1 at 5 or 50 μM in vitro. Dimethoate did not directly inhibit rat testicular steroidogenic enzyme activities at 50 μM. In conclusion, dimethoate targets Star, Cyp11a1, and Hsd3b1 transcription, thus blocking Leydig cell differentiation during puberty.


Ethnic disparities in care and outcomes of non-ST-segment elevation myocardial infarction: a nationwide cohort study.
Little is known about ethnic disparities in care and clinical outcomes of patients admitted with non-ST-segment elevation myocardial infarction (NSTEMI) in national cohorts from universal healthcare systems derived from Europe. We identified 280 588 admissions with NSTEMI in the UK Myocardial Infarction National Audit Project (MINAP), 2010-2017, including White patients (n = 258 364) and Black, Asian, and Minority Ethnic (BAME) patients (n = 22 194). BAME patients were younger (66 years vs. 73 years, P < 0.001) and more frequently had hypertension (66% vs. 54%, P < 0.001), hypercholesterolaemia (49% vs. 34%, P < 0.001), and diabetes (48% vs. 24%, P < 0.001). BAME patients more frequently received invasive coronary angiography (80% vs. 68%, P < 0.001), percutaneous coronary intervention (PCI) (52% vs. 43%, P < 0.001), and coronary artery bypass graft surgery (9% vs. 7%, P < 0.001). Following propensity score matching, BAME compared with White patients had similar in-hospital all-cause mortality [odds ratio (OR) 0.91, confidence interval (CI) 0.76-1.06; P = 0.23], major bleeding (OR 0.99, CI 0.75-1.25; P = 0.95), re-infarction (OR 1.15, CI 0.84-1.46; P = 0.34), and major adverse cardiovascular events (MACE) (OR 0.94, CI 0.80-1.07; P = 0.35). BAME patients with NSTEMI had higher cardiometabolic risk profiles and were more likely to undergo invasive angiography and revascularization, with similar clinical outcomes as those of their White counterparts. Among the quality indicators assessed, there is no evidence of care disparities among BAME patients presenting with NSTEMI.


Patient education at a distance.
Historically, education of patients was paternalistic where people have been conditioned to do as the "doctor" tells them. Traditionally this worked as people tended to have limited access to knowledge of treatment regimen available. However, in the information age, this knowledge is more readily available and it is now common practice to educate people diagnosed with cancer about their treatment and disease process. In fact, dissemination of information is now an intrinsic part of cancer care. The primary aim of this study was to investigate the practice of patient education for gynaecological cancers treated with brachytherapy and review the feasibility of designing a distance learning information tool to inform patients about a clinical treatment option available to them in the cancer agency. The study was divided into two parts. Part 1 was a review of adult learning principles and clinical application. Part 2 explored the feasibility of moving from face-to-face to distance learning in this situation. Adaptation of clinical patient education from a face-to-face learning situation to distance education could be very successful if the basic principles of adult education and facilitation are followed and special care given to maintaining open lines of communication/support for the distant patient.


Solubilization and characterization of hormone- responsive phosphodiesterase activity of rat fat cells.
Fat cells particulate phosphodiesterase activity can be solubilized in high yield (80--100%) in a buffer system (30 mM Tris - HCl, pH 8.0) containing non-ionic detergents (0.1% Brij 30, 1.0% Triton X-100), salt (3.0 mM MgSO4, 5.0 mM NaBr) and dithiothreitol (5.0 mM). Polyacrylamide gel electrophoresis of the solubilized enzyme activity indicated the presence of two bands of activities of different electrophoretic mobilities, both of which hydrolyzed cyclic AMP and cyclic GMP. The solubilized activity eluted from DEAE Bio-Gel columns as a somewhat broad profile with at least two peaks of activity. Activity against both cyclic AMP and cyclic GMP eluted in similar but not identical patterns. The solubilized enzyme and DEAE column eluates wxhibited low (less than 1 micronM) Michaelis constants for cyclic AMP and cyclic GMP. In addition, the increases in phosphodiesterase activity induced by incubation of intact fat cells with insulin or adrenocorticotropic hormone are maintained in the solubilized state.


Residential proximity to heavy traffic and birth weight in Shizuoka, Japan.
An association between exposure to traffic-related air pollution and reduced birth weight has been suggested. However, previous studies have failed to adjust for maternal size, which is an indicator of individual genetic growth potential. Therefore, we evaluated the association of air pollution with birth weight, term low birth weight (term-LBW), and small for gestational age (SGA), with adjustment for maternal size. Individual data were extracted from a database that is maintained by a maternal and perinatal care center in Shizuoka, Japan. We identified liveborn singleton births (n=14,204). Using geocoded residential information, each birth was assigned a number of traffic-based exposure indicators: distance to a major road; distance-weighted traffic density; and estimated concentration of nitrogen dioxide by land use regression. The multivariate adjusted odds ratios and their 95% confidence intervals (CIs) for the associations between exposure indicators and outcomes were then estimated using logistic regression models. Overall, exposure indicators of air pollution showed no clear pattern of association. Although there are many limitations, we did not find clear associations between birth-weight-related outcomes and the three markers of traffic-related air pollution.


Structural and ultrastructural aspects of isolated immature cochlear outer hair cells maintained in short-term culture.
Immature outer hair cells (OHCs), isolated from developing rat cochlea without using proteolytic enzymes, were maintained in short-term culture in a clot of coagulated plasma. Cell viability was assessed by a laser scanning image cytometer, using double-fluorescent labeling. Light and transmission electron microscopy was used to study the morphology of isolated cells. Ten to 60 healthy OHCs were obtained from one cochlea, either as single isolated cells or clusters containing 2-10 cells from the same row. Although dead cells were observed only 1 h after dissociation, there were still viable cells after 6 h. Isolated OHCs were not perfectly cylindrical, due to the immaturity of their cortical structures. One hour after dissociation the ultrastructural organization of the isolated cells was generally well preserved, but this was followed by dilatation of the Golgi apparatus and endoplasmic reticulum. Specific changes in isolated OHCs were also observed at the subsurface cisternae and cuticular plate. Although degenerating OHCs generally showed a classic pattern of necrosis, certain morphological features reminiscent of apoptosis were also observed. This study emphasises the difficulty involved in investigating isolated immature OHCs in vitro and provides a basis for future research into the physiological requirements of isolated immature OHCs.


Zinc Promotes Spinal Cord Injury Recovery by Blocking the Activation of NLRP3 Inflammasome Through SIRT3-Mediated Autophagy.
Spinal cord injuries (SCI) are complex and cause complex neurological disorders with serious implications for the health of society. Excessive neuroinflammation is one of the pathogenesis of trauma-related central nervous system (CNS) dysfunction. The initiation of inflammatory response mainly stems from neuronal necrosis in the central nervous system. The therapeutic effects and underlying mechanisms of zinc targeting neurons were investigated in vivo and in vitro using protein chips, western blotting, reactive oxygen species (ROS) activity assays, ELISA, RT-qPCR, and immunostaining. In this study, we found that zinc promotes functional recovery. Specifically, we found that zinc increased neuronal survival and suppressed lesion size and focal apoptosis levels in vivo. Zinc administration confers neuroprotection by inhibiting NLRP3 inflammasome-associated cytokine levels probed with a protein chip. Furthermore, we found that zinc promoted SIRT3-mediated induction of autophagy, which abrogated inflammatory responses and mitochondrial ROS production in the injured spinal cord and cultured neurons. These findings suggest that zinc improves neuroinflammation and improves dyskinesia after SCI. In conclusion, zinc may be a potential therapeutic immunomodulatory challenge for the treatment of trauma-related CNS dysfunction.


Sea anemone cytolysins as toxic components of immunotoxins.
The use of membrane active toxins as toxic moieties in the construction of immunotoxins (ITs) is an attractive alternative to overcome some of the problems of classical ITs since these new conjugates are based in the use of a different mechanism of killing undesired cells. Pore-forming cytolysins from sea anemones were used in the construction of ITs targeted to different cell types including tumour cell lines and the parasite Giardia duodenalis. The results obtained support the feasibility of directing these cytolysins to the surface of the cancer cells or the parasite through their conjugation to monoclonal antibodies recognizing tumour-associated or parasite antigens, respectively. However the main problem with the IT constructed in this fashion is the lack of specificity associated with the toxin moiety. An approach designed to overcome this limitation was the construction of inactive cytolysin with built-in biological "trigger" that renders the toxin active in the presence of tumour-specific proteinases. This construction is considered as a proof of concept to demonstrate the feasibility of such activation systems in the construction of ITs based on pore-forming cytolysins from sea anemones with reduced unspecific activity. The future prospects of the use of the N-terminal region of actinoporins for construction of IT is also described.


Robustification of GWAS to explore effective SNPs addressing the challenges of hidden population stratification and polygenic effects.
Genome-wide association studies (GWAS) play a vital role in identifying important genes those is associated with the phenotypic variations of living organisms. There are several statistical methods for GWAS including the linear mixed model (LMM) which is popular for addressing the challenges of hidden population stratification and polygenic effects. However, most of these methods including LMM are sensitive to phenotypic outliers that may lead the misleading results. To overcome this problem, in this paper, we proposed a way to robustify the LMM approach for reducing the influence of outlying observations using the β-divergence method. The performance of the proposed method was investigated using both synthetic and real data analysis. Simulation results showed that the proposed method performs better than both linear regression model (LRM) and LMM approaches in terms of powers and false discovery rates in presence of phenotypic outliers. On the other hand, the proposed method performed almost similar to LMM approach but much better than LRM approach in absence of outliers. In the case of real data analysis, our proposed method identified 11 SNPs that are significantly associated with the rice flowering time. Among the identified candidate SNPs, some were involved in seed development and flowering time pathways, and some were connected with flower and other developmental processes. These identified candidate SNPs could assist rice breeding programs effectively. Thus, our findings highlighted the importance of robust GWAS in identifying candidate genes.


Computer-aided detection for screening mammography.
Mammographic film reading is a highly demanding task, particularly in screening programs where the reader must perform a detailed visual search of a large number of images for signs of abnormality that are often subtle or small, and which occur very infrequently. False-negative cases, in which signs of abnormality are missed by a film reader, are known to occur. Computer-aided detection (CAD) systems, which automatically detect potential abnormalities and indicate their locations to the reader, have the capacity to reduce the frequency of such errors by ensuring that all suspicious regions of the images are thoroughly searched and by increasing the weighting attached to subtle signs that may otherwise have been dismissed. CAD systems depend on suites of detection algorithms, but each algorithm has a different sensitivity and specificity and the effect of prompting errors on human performance with CAD is complex. This article is a brief review of CAD for screening mammography; it highlights both the strengths and the weaknesses of the approach, and describes some of the methodologies used to evaluate CAD in a clinical setting.


Strong association of functional polymorphism in IL-12B with susceptibility to chronic hepatitis B in Tunisia.
The chronicity or clearance of hepatitis B virus (HBV) infection depends on viral and genetic variables. The immune response against HBV is thought to be responsible for viral persistence or clearance. Cytokines such as interleukin 1-2B (IL1-2B) involved in the T-helper 1 system are key mediators in the defence mechanisms against viral infection and play a role in the regulation of HBV clearance during infection. We aimed to examine whether the polymorphic variant TaqI polymorphism in the 3'-untranslated region (3'-UTR; rs3212227) suspected to modulate interleukin-levels of IL-12B has an influence on the risk of development of chronicity after HBV exposure. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method for 236 patients with chronic hepatitis B (CHB) and 240 controls from different cities of Tunisia recruited in the Pasteur Institute of Tunisia between January 2017 and December 2018. We found that the IL-12B polymorphism was associated with a significantly increased risk of CHB in patients (p = 1 × 10-3 ; χ 2 = 10.31 and odds ratio [OR] = 2.14; 95% confidence interval [CI] = 1.30-3.52) when AC/CC variant genotypes were compared with the wild-type AA homozygote. Statistical significance was found when CHB-males were compared with CHB-females (p = 2 × 10-7 ; χ 2 = 26.62 and p = 1 × 10-3 ; χ 2 = 10.36, for genotypic and allelic frequencies, respectively). Also, CHB-patients carrying C-allele less than 50-years were at an increased risk of developing chronic HBV infection than patients more than 50-years (p = 6.1 × 10-5 ; χ 2 = 16.07). These results suggest that the C-allele would affect susceptibility to chronicity after HBV exposure in Tunisian patients especially for males less than 50-years. Age and sex have an influence on this polymorphism in CHB Tunisian patients.


Effect of polybutylene adipate terephthalate on the properties of starch/polybutylene adipate terephthalate shape memory composites.
In this work, the starch/polybutylene adipate terephthalate (PBAT) composite films with high starch content were prepared by hot-pressing and ultraviolet cross-linking methods using cassava starch, benzophenone (BP), degradable PBAT and citric acid as film-forming substrate, photosensitizer, toughening material and solvent, respectively. The results showed that starch and PBAT had excellent performance, resulting in the composites films exhibit robust tensile strength (9.90 MPa), decent elongation at break (500.05 %) and excellent shape memory property. Under 30 % pre-tensile strain, the shape memory fixity and recovery ratios reached 96.58 % and 93.94 %, respectively. In addition, the starch-based films were successfully rendered hydrophobic by PBAT hydrophobic characteristics. PBAT not only secures the biodegradability of the starch/PBAT composites films, but also improves the mechanical properties of them, and meets the requirements of the thermal shrinkage films when subjected to large strain.


Pharmacokinetic and pharmacodynamic evaluation of metoprolol controlled release (CR/ZOK) 50 mg in young subjects.
In this steady state, cross-over study, the bioavailability and beta 1-blocking effects of metoprolol CR/ZOK 50 mg, conventional metoprolol 50 mg tablets and placebo were evaluated in 12 healthy male subjects (mean age 25 years) after once daily treatment in 5 days. The drugs were administered in a randomized order. The beta 1-blocking effect was defined as percent reduction from baseline in exercise heart rate. The plasma concentration-time profile following metoprolol CR/ZOK 50 mg administration was more even compared to conventional metoprolol tablets, with significantly lower Cmax (mean: 71 vs 221 nmol/L) and significantly higher Cmin (mean: 39 vs 6 nmol/L) for the CR/ZOK formulation. This difference in plasma concentrations was also well reflected by a significantly lower fluctuation index for metoprolol CR/ZOK 50 mg compared with the conventional 50 mg tablet (mean: 69 vs 529%). There was, however, no difference in systemic bioavailability between the two metoprolol formulations (90% confidence limits: 86-106%). The beta 1-blockade was also more even after metoprolol CR/ZOK 50 mg compared to conventional tablets with a significantly lower Emax (mean: 14 vs 19%) and higher Emin (mean: 9 vs 0%) for CR/ZOK. The total effect over a dosage interval, defined as area under the effect curve, was significantly higher for metoprolol CR/ZOK compared to conventional tablets (90% confidence limits: 123-213%). In conclusion, once daily administration of metoprolol CR/ZOK 50 mg to young healthy subjects resulted in smooth plasma concentration and produced a significant beta 1-blocking effect for 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)


A multicenter randomized controlled trial of surgery alone or surgery with atrial natriuretic peptide in lung cancer surgery: study protocol for a randomized controlled trial.
Postoperative cancer recurrence is a major problem following curative surgery. In a previous retrospective study of lung cancer surgery, we reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduced postoperative recurrence. We demonstrated that ANP inhibited the adhesion of cancer cells to vascular endothelium as a vasoprotective action. The objective of this study is to evaluate the effects of ANP on the incidence of postoperative cancer recurrence in lung cancer surgery. The present study is a multicenter, randomized trial with two parallel groups of patients with lung cancer comparing surgery alone and surgery with ANP administration for 3 days during the perioperative period. A total of 500 patients will be enrolled from 10 Japanese institutions. The primary endpoint is 2-year relapse-free survival (RFS). The secondary endpoints are 2-year cancer-specific RFS, 5-year RFS, overall survival, the incidence of postoperative complications, and the completion rate of ANP treatment. The principal question addressed in this trial is whether ANP with its vasoprotective action can reduce cancer recurrence following lung cancer surgery. UMIN Clinical Trials Registry identifier: UMIN000018480 . Registered on 31 July 2015.


Psychological consequences of the Bam earthquake on professional and nonprofessional helpers.
This study compared the psychological status of rescue personnel who had formal training (Red Crescent workers, i.e., Red Cross workers, and firefighters) with university student volunteers who had no formal training in handling traumatic situations in the Bam earthquake. One hundred student volunteers, 18 Red Crescent workers, and 36 firefighters participated in this study. Participants completed the Civilian Mississippi Scale, the General Health Questionnaire (GHQ-28), and the Anxiety Sensitivity Index. Helpers without formal training showed higher scores on posttraumatic stress disorder (PTSD) and GHQ subscales compared to trained rescue personnel. In addition, a significant number of volunteers without formal training met criteria for a possible PTSD diagnosis by scoring above the cut-off point for the Mississippi scale. Those who had higher scores on the Anxiety Sensitivity Index showed greater adverse psychological effects.