Periurethral muscle-derived mononuclear cell injection improves urethral sphincter restoration in rats.
Investigate the effect of a novel cell-based therapy with skeletal muscle-derived mononuclear cells (SMDMCs) in a rat model of stress urinary incontinence. Male Wistar-Kyoto rats' hind limb muscles were enzymatically dissociated, and SMDMCs were isolated without needing expansion. The cell population was characterized. Twenty female rats underwent urethrolysis. One week later, 10 rats received periurethral injection of 106 cells (SMDMC group), and 10 rats received saline injections (Saline group). Ten rats underwent sham surgery (Sham group). Four weeks after injection, animals were euthanized and the urethra was removed. The incorporation of SMDMCs in the female urethra was evaluated with fluorescence in situ hybridization for the detection of Y-chromosomes. Hematoxylin and eosin, Masson's trichrome staining, and immunohistochemistry for actin and myosin were performed. The muscle/connective tissue, actin and myosin ratios were calculated. Morphological evaluation of the urethral diameters and fractional areas of the lumen, mucosa, and muscular layer was performed. SMDMCs population was consistent with the presence of muscle cells, muscle satellite cells, perivascular cells, muscle progenitor cells, and endothelial cells. SMDMCs were incorporated into the urethra. A significant decrease in the muscle/connective tissue ratio was observed in the Saline group compared with the SMDMC and Sham groups. The proportions of actin and myosin were significantly decreased in the Saline group. No differences were observed in the morphometric parameters. SDMSC were incorporated into the rat urethra and promoted histological recovery of the damaged urethral sphincter, resulting in decreased connective tissue deposition and increased muscle content.


[Case-control study on two different approaches for the treatment of thoracolumbar fracture without neurological symptoms].
To investigate the clinical effects of two surgical approaches for the treatment of thoracolumbar fracture without neurological symptoms. From January 2008 to December 2009, 40 cases with thoracolumbar fractures without neurological symptoms treated by surgery were respectively analyzed. Among the patients, there were 13 males and 27 females, with an average age of 46 years (ranged, 26 to 61 years). Twenty patients in group A treated through posterior median approach; twenty patients in group B were treated through paraspinal muscle approach. All the patients were received the same posterior spinal internal fixation (Sofamor Inc (Basis)). Operating time, blood loss, postoperative drainage, postoperative bed time, VAS score 24 and 72 hours after operation, postoperative Cobb angle correction rate, correction rate of vertebral collapse were analyzed. There were no significant difference in postoperative Cobb angle correction rate and vertebral collapse rate (P < 0.05); while the index such as operating time, blood loss, postoperative drainage, postoperative bed time and VAS score 24 h and 72 h after operation in group B is better than group A. Treatment of thoracolumbar fracture through posterior median approach has an advantage of minimal invasive, less bleeding and rapidly recovery, but the patients with neural symptoms and intraspinal occupying more than 1/3 is not suggested.


Post-ischemic myocardial function after pre-ischemic application of propranolol or verapamil.
The influence of pre-ischemic treatment with propranolol (0.8 mg/kg bw) or with verapamil (0.1 mg/kg bw) on myocardial O2 consumption and on coronary resistance after cardioplegic arrest (300 minutes at 22 degrees - 24 degrees C) was investigated, using a Langendorff technique in open chest experiments (canine hearts). For myocardial protection histidine buffered Bretschneider solution was used, while for standardization all hearts were postischemically reperfused with a modified Tyrode solution at 35 degrees C. Both drugs were given intravenously in two fractions, 60 and 30 minutes before the onset of cardioplegic perfusion; a third group was not pretreated. Although the verapamil group had the lowest O2 consumption post-ischemically, the most impressive results were found in coronary resistance. Propranolol significantly diminished coronary resistance (p less than 0.05), while verapamil distinctly enhanced it compared to the non treated group. The "membrane labilizing" effect of verapamil combined with calcium-free cardioplegic solution was confirmed by a massive postischemic myocardial sodium uptake.


Mechanisms of Type I interferon cell signaling and STAT-mediated transcriptional responses.
The interferons are pleiotropic cytokines that are induced in response to virus infection and act in a paracrine fashion to elicit an antiviral state in nearby cells. Binding of interferons to their cell surface receptors induces a tyrosine kinase signaling cascade that leads to the activation of latent cytoplasmic signal transducer and activator of transcription (STAT) factors. Activated STATs then translocate into the nucleus and are targeted to conserved promoter-enhancer sites to induce the transcription of interferon-responsive genes that encode for proteins with potent antiviral, growth-inhibitory, antitumor, and immunomodulatory properties. Although the signaling and activation phase of the interferon response has been well characterized, several recent findings have further clarified the cellular events that immediately follow STAT activation, including the identification of the amino acid signals that regulate the subcellular distribution of interferon- signaling proteins. To achieve their full transcriptional capacity, members of the STAT family of transcription factors have been shown to require interactions with an assortment of nuclear transcriptional co-activator proteins. A number of the STAT co-activator protein partners have only been identified recently. Some of these interactions suggest cross-talk with other signaling pathways, thereby reaffirming the far-reaching, yet undiscovered, properties of interferons.


Smoking and depression in Chinese Americans.
A close link between smoking and depression has been documented by research primarily based on U.S. white populations. This study examined the association between depressive symptoms and smoking behaviors in Chinese American smokers. Analyses were based on baseline data collected from a convenience sample of 199 Chinese smokers who resided in northern California. The sample included 20.6% women, 97% immigrants, with mean age of 40.8 years and mean cigarettes/day of 8.9. Compared with population-based studies of Chinese Americans, the Chinese smokers in the current study reported higher depressive symptoms assessed by the Center for Epidemiologic Studies-Depression Scale [M, 20.4; 95% confidence interval (CI), 18.8-22.2], higher lifetime prevalence rates of major depressive disorders (30.3%; 95% CI, 24.0-37.2%) and dysthymia (11.6%; 95% CI, 7.5-16.9%). Multiple regression analysis suggested female gender, unemployment, major depression or dysthymia within the past year, previous experience with nicotine withdrawal syndrome, and high temptation to smoke under negative affect situations are associated with a higher level of depressive symptoms. The level of depressive symptoms among Chinese American smokers is comparable with that observed in other US populations reported. In the current sample, elevated depressive symptoms were more prominent among women or those who were unemployed, smokers who reported significant nicotine withdrawal at previous quit attempts, and high temptation to smoke when experiencing negative emotions. Findings support further examination of the role of depression in smoking among Chinese Americans and underscore the importance of addressing depressive symptoms when treating tobacco use in Chinese smokers.


Correlation between auditory function and internal auditory canal pressure in patients with vestibular schwannomas.
Hearing loss is the most common presenting symptom in patients who harbor a vestibular schwannoma (VS). Although mechanical injury to the cochlear nerve and vascular compromise of the auditory apparatus have been proposed, the exact mechanism of this hearing loss remains unclear. To test whether pressure on the cochlear nerve from tumor growth in the internal auditory canal (IAC) is responsible for this clinical finding, the authors prospectively evaluated intracanalicular pressure (ICaP) in patients with VS and correlated this with preoperative brainstem response. In 40 consecutive patients undergoing a retrosigmoid-transmeatal approach for tumor excision, ICaP was measured by inserting a pressure microsensor into the IAC before any tumor manipulation. Pressure recordings were correlated with tumor size and preoperative auditory evoked potential (AEP) recordings. The ICaP, which varied widely among patients (range 0-45 mm Hg), was significantly elevated in most patients (median 16 mm Hg). Although these pressure measurements directly correlated to the extension of tumor into the IAC (p = 0.001), they did not correlate to total tumor size (p = 0.2). In 20 patients in whom baseline AEP recordings were available, the ICaP directly correlated to wave V latency (p = 0.0001), suggesting that pressure from tumor growth in the IAC may be responsible for hearing loss in these patients. Tumor growth into the IAC results in elevation of ICaP and may play a role in hearing loss in patients with VS. The relevance of these findings to the surgical treatment of these tumors is discussed.


[Survey on knowledge of healthy life style among permanent and temporary residents living in the communities of Beijing].
To understand the current situation of knowledge on healthy life style among 'typical' community residents in Beijing. In 2004 and 2005,1765 permanent residents above 15 years old from 600 families living in the 'typical' communities since 2000, were selected to provide baseline data from answering the 'Beijing Typical Community Resident Questionnaire' designed by the local researchers. Data on the knowledge of healthy life style including healthy behavior,general status on health, physical activity and the use of sports facilities were gathered. In 2006, same questionnaire was used to compare with the previous data. The percentage of overall knowledge on health among permanent residents from those 'typical' communities in 2006 was higher than those in the baseline study. The percentage of people who were aware of knowledge on "no-smoking", "intake less salt", "maintaining healthy diet program" and "insisting on exercise" were 72.97%, 93.11%, 86.58% and 87.25% respectively in 2006, higher than 67.38%, 89.74%, 82.12% and 82.78% during the baseline (P < 0.01) study in the previous years. The percentage of correct answer about the healthy life style as diet and prevention of common diseases was higher among the permanent residents than those of temporary residents in 2006 (P < 0.05). The sources of health-related knowledge were mainly from media, newspapers and through health education programs carried out in the community. The Beijing municipal government and the community residential committees attached great importance to providing knowledge on healthy life style to the 'typical' communities which had led to a higher statistics than previous years.


Cytoprotective effects of hydrogen sulfide-releasing N-methyl-D-aspartate receptor antagonists are mediated by intracellular sulfane sulfur.
Hydrogen sulfide (H2S) exerts a host of biological effects ranging from cytotoxicity to cytoprotection. Cytotoxicity of H2S in neurodegenerative diseases may be mediated by N-methyl-D-aspartate receptor (NMDAR) activation. To exploit cytoprotective effects of H2S while minimizing its toxicity, we synthesized a series of H2S-releasing NMDAR antagonists and examined their effects against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death, a cellular model of Parkinson's disease. We observed that cytoprotective effect of H2S-releasing NMDAR antagonists correlated with their ability to increase intracellular sulfane sulfur, but not H2S, levels. These studies suggest that H2S-donor compounds that increase intracellular sulfane sulfur are potentially useful neuroprotective agents against neurodegenerative diseases.


Autolysis of the millimolar Ca2+-requiring form of the Ca2+-dependent proteinase from chicken skeletal muscle.
The millimolar Ca2+-requiring form of the Ca2+-dependent proteinase from chicken breast skeletal muscle contains two subunit polypeptides of 80 and 28 kDa, just as the analogous forms of this proteinase from other tissues do. Incubation with Ca2+ at pH 7.5 causes rapid autolysis of the 80-kDa polypeptide to 77 kDa and of the 28-kDa polypeptide to 18 kDa. Autolysis of the 28-kDa polypeptide is slightly faster than autolysis of the 80-kDa polypeptide and is 90-95% complete after 10 s at 0 degrees C. Autolysis for 15 s at 0 degrees C converts the proteinase from a form requiring 250-300 microM Ca2+ to one requiring 9-10 microM Ca2+ for half-maximal activity, without changing its specific activity. The autolyzed proteinase has a slightly lower pH optimum (7.7 vs. 8.1) than the unautolyzed proteinase. The autolyzed proteinase is not detected in tissue extracts made immediately after death; therefore, the millimolar Ca2+-requiring proteinase is largely, if not entirely, in the unautolyzed form in situ.


Potential therapeutic biomarkers in plasma cell myeloma: a flow cytometry study.
To investigate the expression profile of potential therapeutic biomarkers in plasma cell myeloma (PCM) by multicolor flow cytometry analysis. Bone marrow (BM) specimens were collected consecutively and analyzed using a routine PCM panel (CD38/CD138/CD45/CD19/CD20/CD28/CD56/CD117, cyto-kappa/lambda). The specimens were further assessed for CD30, CD44, CD49d, CD70, CD105, and CD184 expression in cases containing a substantial number of neoplastic plasma cells. Totally, 101 patient BM samples were assessed, including 58 men and 43 women, with a median age of 64 years (34-89). Twenty-nine patients had newly diagnosed/untreated PCM, 40 had persistent/residual disease undergoing various therapies and 32 had relapsed disease. CD49d was expressed brightly and uniformly in all 45 patients tested. Expression of CD44 and CD184 was more variable with a median percentage of 77% (1-100) and 65% (5-100) respectively. Using an arbitrary 20% cutoff, CD44 was positive in 74 (73%) and CD184 in 92 (91%) cases with a mean fluorescence intensity ratio of 42.8 and 21.4. A higher CD44 expression was observed in patients with recurrent/persistent disease (P = 0.028). Additionally, both CD44 (P = 0.002) and CD184 (P = 0.026) showed higher expressions in CD117-positive cases, but there was no correlation with cytogenetic groups. The CD30, CD70, and CD105 were expressed very infrequently in PCM, with a median expression of 0.2%, 0.2%, and 0.4% respectively. CD49d, CD44, and CD184, are highly expressed in PCM. CD49d expression is bright and uniform, whereas CD44 and CD184 are more heterogeneous. In contrast, surface CD30, CD70, and CD105 are infrequent. These data provide useful preclinical information for the design of potential novel targeted therapies in PCM patients.


Identification of the driving factors' influences on regional energy-related carbon emissions in China based on geographical detector method.
To investigate the influences of different factors on spatial heterogeneity of regional carbon emissions, we firstly studied the spatial-temporal dynamics of regional energy-related carbon emissions using global Moran's I and Getis-Ord Gi and applied geographical detector model to explain the spatial heterogeneity of regional carbon emissions. Some conclusions were drawn. Regional carbon emissions showed significant global and local spatial autocorrelation. The carbon emissions were greater in eastern and northern regions than in western and southern regions. Fixed assets investment and economic output had been the main contributing factors over the study period, and economic output had been decreasing its influence. Industrial structure's influence showed a decrease trend and became smaller in 2015. The results of the interaction detections in 2015 can be divided into two types: enhance and nonlinear, and enhance and bivariate. The interactive influences between technological level and fixed assets investment, economic output and technological level, population size and technological level, and economic output and economic development were greater than others. Some policy recommendations were proposed.


Trends in reperfusion strategies, door-to-needle and door-to-balloon times, and in-hospital mortality among patients with ST-segment elevation myocardial infarction enrolled in the National Registry of Myocardial Infarction from 1990 to 2006.
Among patients with ST-segment elevation myocardial infarction (STEMI), rapid reperfusion is associated with improved mortality. As such, door-to-needle (D2N) and door-to-balloon (D2B) times have become metrics of quality of care and targets for intense quality improvement. The National Registry of Myocardial Infarction (NRMI) collected data regarding reperfusion therapy, its timing and in-hospital mortality among STEMI patients from 1990 through 2006. Since 1990, NRMI has enrolled 1,374,232 STEMI patients at 2,157 hospitals. Among those, 774,279 (56.3%) were eligible for reperfusion upon arrival. The proportion receiving fibrinolytic therapy fell from 52.5% in 1990 to 27.6% in 2006 (P < .001), while the proportion undergoing primary percutaneous coronary intervention (pPCI) increased from 2.6% to 43.2%. Among reperfusion-eligible patients who received fibrinolytic therapy, there was a nearly linear decline in median D2N time from 59 minutes in 1990 to 29 minutes in 2006 (P < .001 for trend) as well as a decrease in mortality from 7.0% in 1994 to 6.0% in 2006 (P < .001). Among those undergoing pPCI, D2B time among nontransfer patients declined linearly from 111 minutes in 1994 to 79 minutes in 2006 (P < .001) with a decline in mortality from 8.6% to 3.1% (P < .001). The relative improvement in mortality attributable to improvements in D2N time was 16.3% and to D2B time was 7.5%. Since 1990, there has been a progressive decline in D2N and D2B time among reperfusion-eligible STEMI patients. These improvements have contributed, at least in part, to a progressive decline in mortality.


[Correlations between left atrial size and parameters of averaged atrial signal in patients with paroxysmal atrial fibrillation in the course of ischemic heart diseases].
The aim of this study was to assess the correlation between left atrial size and atrial signal-averaged electrocardiogram (ALP) in time-domain and frequency analysis in patients with paroxysmal atrial fibrillation (PAF) during ischaemic heart disease (IHD). The study population consisted of 75 patients with PAF during IHD who were divided into two groups; gr. I (left atrial dimension 40 mm) and gr. II (left atrial dimension 40 mm). The control group (gr. III) consisted of 50 healthy subjects. Recording of ALP was carried out by HIPEC-200HA. The high gain ECG was recorded during basic rhythm with orthogonal Frank leads X,Y,Z. These signals were amplified, averaged and filters. The filtered signals were combined into a vector magnitude and time-domain and frequency analysis was done. These findings suggest that the size of the left atrium does not change time-domain and frequency parameters of ALP in patients with PAF and IHD. We noticed significant influence of IHD on these parameters. On the other hand frequency analysis of ALP did not show any uselessness in diagnostic identification of patients with PAF during IHD and healthy subjects.


Pathophysiologic classification of peripheral vascular disease by positional changes in regional transcutaneous oxygen tension.
The clinical manifestations and prognosis of peripheral vascular disease (PVD) depend upon the severity of limb hypoxia. Transcutaneous oxygen tension (Ptco2) is related to tissue oxygenation, but limb Ptco2 varies with changes in systemic as well as peripheral oxygen delivery (Do2). Previously we have found that simultaneous assessment of limb and chest Ptco2 yields a ratio, or regional perfusion index (RPI), that is independent of systemic Do2 and accurately reflects the adequacy of limb perfusion. Analysis of segmental limb Ptco2, RPI, and position-induced RPI changes was performed in 24 control limbs and 14 limbs with intermittent claudication (IC), 8 limbs with rest pain (RP), and 7 limbs with gangrene (G). Control limbs had high RPI values that varied little with position. The IC group had modestly decreased RPIs in the supine position, but extremity RPIs decreased markedly during leg elevation. Patients with RP had ischemia while supine, but the RPI improved to nearly normal upon standing. Feet with G were hypoxic even in the standing position. Segmental RPI decreases correlated with the presence of significant arterial lesions. This correlation was unaffected by diabetes. Analysis of regional transcutaneous oximetry allows classification of PVD by quantitative criteria based upon the adequacy of limb perfusion under functional conditions. RPI is characteristically high in normal persons and low in persons with G. Limbs with marginally compensated perfusion may have nearly normal RPI values under some conditions, but typical ischemic changes are elicited by positional change and exercise. The ease of such provocation of RPI decreases constitutes an index of the severity of disease. Such quantitative assessments of limb hypoxia can form the basis for a physiologic approach to arterial reconstruction.


Results of modified Latarjet reconstruction in patients with anteroinferior instability and significant bone loss.
The purpose of this study was to analyze the results of the modified Latarjet procedure for shoulder instability associated with an inverted-pear glenoid (bone loss of at least 25% of the width of the inferior glenoid) or an engaging Hill-Sachs lesion. From March 1996 to December 2002, 102 patients underwent an open Latarjet procedure for shoulder instability with an inverted-pear glenoid, with or without an associated engaging Hill-Sachs lesion, by the 2 senior authors (S.S.B. and J.F.D.), and 47 of them were available for follow-up physical examination. The remaining 55 patients were contacted by telephone or letter to see if they had had recurrent dislocation or subluxation. The mean age of the patients was 26.5 +/- 6.6 years (range, 16 to 41 years). There were 46 male patients and 1 female patient. Preoperatively, mean forward elevation was 177.2 degrees +/- 13.6 degrees (range, 90 degrees to 180 degrees) and mean external rotation with the arm at the side was 55.3 degrees +/- 16.1 degrees (range, 0 degrees to 80 degrees). All patients had a positive apprehension sign preoperatively. The median number of dislocations before surgery was 6, with 20 patients having had more than 15 dislocations preoperatively. The mean follow-up time for the 47 patients who were personally examined was 59.0 +/- 18.5 months (range, 32 to 108 months). Postoperatively, mean forward elevation was 179.6 degrees +/- 2.0 degrees (range, 170 degrees to 180 degrees; gain of 2.4 degrees) and external rotation with the arm at the side was 50.2 degrees +/- 12.6 degrees (range, 22 degrees to 78 degrees; loss of 5.1 degrees). As for postoperative functional scores, the mean Constant score was 94.4 and the mean Walch-Duplay score was 91.7. None of these 47 patients showed any further dislocation, and 1 of them still had a positive apprehension sign (2.2%) indicating subluxation. However, 4 patients out of the total 102 who underwent the modified Latarjet procedure had a recurrence. With 4 recurrent dislocations and 1 recurrent subluxation, there was a 4.9% recurrence rate. The 4 patients with recurrent dislocations were not among the 47 who returned for personal follow-up evaluation. The 2 senior authors (S.S.B. and J.F.D.) have previously reported an unacceptably high recurrence rate (67%) for arthroscopic Bankart repair in the presence of an inverted-pear glenoid with or without an engaging Hill-Sachs lesion. They have recommended an open modified Latarjet procedure in such patients. The present study confirms the validity of that recommendation, because the same 2 surgeons have had only a 4.9% recurrence rate in that same category of patient at a mean follow-up of 59 months. Furthermore, the results of this study show the efficacy of the modified Latarjet procedure in the extremely challenging category of patients who present with such dramatic bone loss that soft-tissue reconstruction, either open or arthroscopic, is not a reasonable option. Level IV, therapeutic case series.


Nonimmunologic mechanisms of glomerular injury.
From the above discussion it is clear that many factors have been invoked in the pathogenesis of progressive glomerular injury. Those which are most important include increased PGC, coagulation, serum lipid abnormalities, and hypertrophy. Although many hemodynamic alterations have been identified, increased PGC was noted most constantly. Furthermore, the loss of autoregulatory capability which was observed in some models with progressive glomerulosclerosis usually resulted in increased PGC. Increased PGC has been associated with augmented dietary protein and is seen in the Munich-Wistar rat made diabetic. Such an increase in PGC could cause direct mechanical injury to endothelial and epithelial cells, as well as be responsible for increased mesangial traffic of macromolecules with the potential for stimulating cellular proliferation and mesangial matrix increase. Additional support for the importance of increased PGC is provided by the protective effect of decreasing PGC with CEI therapy and anemia, and by the enhanced autoregulatory capability in both the Milan and Okamoto hypertensive rats. The significance of coagulation factors is confirmed by the formation of platelet and fibrin thrombi in the development of the glomerular lesions. The sequence of glomerular injury suggests that endothelial damage occurs with subsequent formation of platelet aggregates as a response to this injury. Formation of platelet aggregates may be associated with the production of substances potentially injurious to the endothelial cells. Although blocking the appearance of such thrombi by administration of heparin or thromboxane synthetase inhibitor prevents glomerular injury, the blood pressure lowering effect of these agents complicates the interpretation of the studies. Serum lipid abnormalities are also important factors in the progression of nonimmunologic glomerular injury. Such abnormalities are observed with increased dietary phosphorus or lipid, in the obese Zucker rat, and in rats with diabetes mellitus. Reduction in serum cholesterol by administration of clofibric acid or mevinolin diminishes glomerular injury independent of alterations in glomerular hemodynamics. The possible link between increased serum lipids and augmentation of glomerular injury is at present indirect. The importance of hypertrophy as a contributing factor to the progression of nonimmunologic glomerular injury is suggested by several lines of evidence. Hypertrophy, with increase in glomerular size and caliber of capillary loops, may amplify the effect of increased PGC by further intensifying the tension and mechanical stress on all elements of the capillary wall.(ABSTRACT TRUNCATED AT 400 WORDS)


Correlation of Salivary Statherin and Calcium Levels with Dental Calculus Formation: A Preliminary Study.
Salivary constituents have a wide range of functions including oral calcium homeostasis. Salivary proteins such as statherin inhibit crystal growth of calcium phosphate in supersaturated solutions and interact with several oral bacteria to adsorb on hydroxyapatite. Concurrently, saliva, which is supersaturated with respect to calcium phosphates, is the driving force for plaque mineralization and formation of calculus. Thus, the aim of the present study was to estimate and correlate salivary statherin and calcium concentration to the dental calculus formation. A cross-sectional study was conducted to assess the relationship between salivary statherin, calcium, and dental calculus among 70 subjects, aged 20-55 years. Subjects were divided into 3 groups based on the calculus scores as interpreted by Calculus Index which was followed by collection of whole saliva using Super•SAL™. Salivary calcium levels were assessed by calorimetric method using Calcium Assay kit (Cayman Chemical, Michigan, USA) and statherin levels by using ELISA Kit (Cusabio Biotech). Statherin levels showed a weak negative correlation with the calcium levels and with calculus formation. The mean salivary statherin and calcium concentration were found to be 0.96 μg/ml and 3.87 mg/ml, respectively. Salivary statherin levels differed significantly among the three groups (p < 0.05). Our preliminary data indicates that statherin could possibly play a role in the formation of dental calculus.


Phase I Clinical Trial Using Autologous Ex Vivo Expanded NK Cells and Cytotoxic T Lymphocytes for Cancer Treatment in Vietnam.
(1) Background: Immune cell therapy recently attracted enormous attention among scientists as a cancer treatment, but, so far, it has been poorly studied and applied in Vietnam. The aim of this study was to assess the safety of autologous immune cell therapy for treating lung, liver, and colon cancers-three prevalent cancers in Vietnam. (2) Method: This was an open-label, single-group clinical trial that included 10 patients with confirmed diagnosis of colon, liver, or lung cancer, conducted between March 2016 and December 2017. (3) Results: After 20-21 days of culture, the average number of cytotoxic T lymphocytes (CTLs) increased 488.5-fold and the average cell viability was 96.3%. The average number of natural killer cells (NKs) increased 542.5-fold, with an average viability of 95%. Most patients exhibited improved quality of life, with the majority of patients presenting a score of 1 to 2 in the Eastern Cooperative Oncology Group (ECOG) performance status (ECOG/PS) scale, a decrease in symptoms on fatigue scales, and an increase in the mean survival time to 18.7 months at the end of the study. (4) Conclusion: This method of immune cell expansion met the requirements for clinical applications in cancer treatment and demonstrated the safety of this therapy for the cancer patients in Vietnam.


Extracorporeal carbon dioxide removal compared to ventilation alone in patients with acute hypoxaemic respiratory failure: cost-utility analysis of the REST RCT.
Acute hypoxaemic respiratory failure requiring mechanical ventilation is a major cause of morbidity and mortality and has significant resource implications in terms of intensive care unit and hospital stay. To assess the cost-effectiveness of extracorporeal carbon dioxide removal compared to ventilation alone in patients with acute hypoxaemic respiratory failure. A cost-utility analysis embedded within a pragmatic, multicentre, allocation-concealed, open-label, randomised controlled trial. Four hundred and twelve (of a planned sample size of 1120) adult patients receiving mechanical ventilation for acute hypoxaemic respiratory failure, were recruited between May 2016 and December 2019 from 51 intensive care units in the UK. Participants were randomised (1 : 1) to receive extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with ventilation alone (n = 210). Health-related quality of life via the EuroQol-5 Dimensions, five-level version, health resource use and associated costs were measured over the study period. The cost per quality-adjusted life-year was estimated at 12 months post randomisation. Mean EuroQol-5 Dimensions, five-level version utility scores were low and similar for each group. Quality-adjusted life-years were calculated for those patients with complete EuroQol-5 Dimensions, five-level version data (extracorporeal carbon dioxide removal n = 140, ventilation alone n = 143) and there was no discernible difference in quality-adjusted life-years at 12 months (mean difference -0.01; 95% confidence interval -0.06 to 0.05; 140). Total 12-month health resource use cost (including intervention costs) was calculated for those patients with complete cost data (extracorporeal carbon dioxide removal n = 125, ventilation alone n = 126) and costs were statistically significantly higher in the extracorporeal carbon dioxide removal group (mean difference £7668.76, 95% confidence interval 159.75, 15,177.77). Multiple imputation was used for missing total cost and quality-adjusted life-year data in the cost-utility analysis. Ventilation alone dominated extracorporeal carbon dioxide removal and there was 0% probability of extracorporeal carbon dioxide removal being cost-effective compared to ventilation alone for all willingness to pay thresholds per quality-adjusted life-year considered (£0-50,000). Extracorporeal carbon dioxide removal was associated with significantly higher costs, but no benefit in health-related quality of life. Given the data, extracorporeal carbon dioxide removal is not considered to be a cost-effective approach to treating patients with acute hypoxaemic respiratory failure. These included the absence of a baseline healthy utility score, minor data loss related to not obtaining complete intensive care unit readmission data for Scottish participants, and not estimating long-term cost-effectiveness due to the study closing early. Measuring baseline health-related quality of life in critical care studies is difficult; future economic evaluations in this setting should consider measuring health-related quality of life as soon as possible after the patients regain capacity. This trial is registered as NCT02654327 and ISRCTN 31262122. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 13/143/02.


Differential evolution algorithm based photonic structure design: numerical and experimental verification of subwavelength λ/5 focusing of light.
Photonic structure designs based on optimization algorithms provide superior properties compared to those using intuition-based approaches. In the present study, we numerically and experimentally demonstrate subwavelength focusing of light using wavelength scale absorption-free dielectric scattering objects embedded in an air background. An optimization algorithm based on differential evolution integrated into the finite-difference time-domain method was applied to determine the locations of each circular dielectric object with a constant radius and refractive index. The multiobjective cost function defined inside the algorithm ensures strong focusing of light with low intensity side lobes. The temporal and spectral responses of the designed compact photonic structure provided a beam spot size in air with a full width at half maximum value of 0.19λ, where λ is the wavelength of light. The experiments were carried out in the microwave region to verify numerical findings, and very good agreement between the two approaches was found. The subwavelength light focusing is associated with a strong interference effect due to nonuniformly arranged scatterers and an irregular index gradient. Improving the focusing capability of optical elements by surpassing the diffraction limit of light is of paramount importance in optical imaging, lithography, data storage, and strong light-matter interaction.


Quality of life after Nissen-Rossetti fundoplication.
We investigated Quality of Life (QoL) and Johnsson & DeMeester score of patients after Nissen-Rossetti fundoplication. From January 2007 to June 2008, 43 patients with chronic gastroesophageal reflux underwent laparoscopic Nissen-Rossetti fundoplication; 7 were lost during the follow-up. Patients underwent endoscopy, 24-hour pH-metry, Gastroesophageal Reflux Disease-Health-Related Quality-of-Life (GERD-HRQL), and Short Form 36 (SF-36) questionnaires preoperatively, 6 months, and 12 months after surgery. Endoscopic findings revealed complete healing of esophagitis in all patients. Barrett esophagus was still present. Six patients reported persistence of symptoms but postoperative pH-metry and endoscopy showed the absence of reflux; 2 patients (5.5%) were still on proton pump inhibitor therapy at 12 months. Seven patients (19.4%) reported dysphagia for solids for at least 3 months. Readmission for dysphagia was required for 2 (5.5%) and 1 patient underwent endoscopic dilatation. At 6 and 12 months, no dysphagia was reported. During the follow-up, no gas-bloat syndrome was reported. The Johnsson & DeMeester score and QoL measurement obtained from GERD-HRQL and SF-36 revealed a significant improvement in the related domain. At 6 months, 23 patients (63.8%) were completely satisfied and after 12 months, 30 patients (83.3%) were satisfied. Nissen-Rossetti fundoplication is safe and effective for the treatment of GERD, improving QoL.


Subcorneal pustular dermatosis: a clinical study of ten patients.
Subcorneal pustular dermatosis of Sneddon and Wilkinson (SPD) is a unique clinical and histologic entity. This disorder has been reported in association with monoclonal gammopathy and IgA pemphigus. We report ten additional cases of SPD and determine the frequency of monoclonal gammopathy and IgA pemphigus in patients with SPD and investigate the relationship of this entity with other dermatoses characterized histologically by a subcorneal pustule. The medical records of patients with SPD evaluated at the authors' institution from 1980 through 1995 were reviewed retrospectively. Medical records of twenty patients with pustular psoriasis were reviewed for comparison. Ten patients met the criteria for SPD. Their average age at diagnosis was 66 years. The characteristic flaccid pustules were often generalized and had a tendency to involve the flexural areas. Serum monoclonal gammopathy was present in four patients: three with IgA and one with IgG. On direct immunofluorescence examination, three patients had IgA deposits in the intercellular spaces. None of the patients exhibited both monoclonal gammopathy and IgA deposits. Repeated direct immunofluorescence studies were necessary to detect IgA pemphigus in one patient. SPD is a distinct clinical entity. The findings of IgA deposits intercellularly on immunofluorescence and monoclonal gammopathy may help to further identify this entity.


Effects of long-term diabetes and/or high-dose 17 beta-estradiol on bone formation, bone mineral density, and strength in ovariectomized rats.
Long-term diabetes in female rats preserves the bone mineral density (BMD) but impairs the strength of the femur. In this study, we have compared the effects of diabetes and high-dose 17 beta-estradiol (E2), two conditions of low bone formation, in ovariectomized (ovx) rats. Spontaneously diabetic BB rats were ovx 0-3 days after onset, and nondiabetic ovx littermates were used as controls; the rats were either untreated or treated with E2 (30 micrograms/day, subcutaneously), for 6 or 12 weeks (n = 9 in each of the eight groups). Analysis included: plasma 1,25-dihydroxyvitamin D3, insulin-like growth factor-I (IGF-I), and osteocalcin concentrations; histomorphometry of the proximal tibial metaphysis (PTM); and DXA and biomechanical testing of the femur. Both E2 treatment and diabetes markedly lowered plasma IGF-I and osteocalcin concentrations, as well as dynamic morphometric parameters of bone formation in the PTM. Plasma IGF-I and osteocalcin were correlated (R2 = 0.55; p < 0.0001). E2 treatment in both control and diabetic ovx rats increased the trabecular bone volume in the PTM and the BMD in the metaphysis of the distal femur; there was no difference between control and diabetic rats, however. The diaphyseal area and BMC were decreased in E2-treated or/and diabetic ovx rats, but the diaphyseal BMD remained unchanged compared with untreated ovx rats. The biomechanical properties of the whole femur (strength, angular deformation, and stiffness) were decreased in E2-treated and diabetic E2-treated ovx rats after 12 weeks. The data indicate that in situations of chronic low bone formation, whole bone strength does not reflect total BMD but correlates better with bone size and bone mineral content measurements.


Polymer gel dosimetry close to an 125I interstitial brachytherapy seed.
Despite its advantages, the polymer gel-magnetic resonance imaging (MRI) method has not, as yet, been successfully employed in dosimetry of low energy/low dose rate photon-emitting brachytherapy sources such as 125I or 103Pd interstitial seeds. In the present work, two commercially available 125I seed sources, each of approximately 0.5 U, were positioned at two different locations of a polymer gel filled vial. The gel vial was MR scanned with the sources in place 19 and 36 days after seed implantation. Calibration curves were acquired from the coupling of MRI measurements with accurate Monte Carlo dose calculations obtained simulating the exact experimental setup geometry and materials. The obtained gel response data imply that while linearity of response is sustained, sensitivity (calibration curve slope) is significantly increased (approximately 60%) compared to its typical value for the 192Ir (or 60Co and 6 MV LINAC) photon energies. Water equivalence and relative energy response corrections of the gel cannot account for more than 3-4% of this increase, which, therefore, has to be mainly attributed to physicochemical processes related to the low dose rate of the sources and the associated prolonged irradiation time. The calibration data obtained from one 125I source were used to provide absolute dosimetry results for the other 125I source, which were found to agree with corresponding Monte Carlo calculations within experimental uncertainties. It is therefore suggested that, regardless of the underlying factors accounting for the gel dose response to 125I irradiations, polymer gel dosimetry of new 125I or 103Pd sources should be carried out as originally proposed by Heard and Ibbot (2004 J. Phys.: Conf. Ser. 3 221-3), i.e., by irradiating the same gel sample with the new low dose rate source, as well as with a well-characterized low dose rate source which will provide the dose calibration curve for the same irradiation conditions.


Transcriptome analysis reveals molecular mechanisms of lymphocystis formation caused by lymphocystis disease virus infection in flounder (Paralichthys olivaceus).
Lymphocystis disease is frequently prevalent and transmissible in various teleost species worldwide due to lymphocystis disease virus (LCDV) infection, causing unsightly growths of benign lymphocystis nodules in fish and resulting in huge economic losses to aquaculture industry. However, the molecular mechanism of lymphocystis formation is unclear. In this study, LCDV was firstly detected in naturally infected flounder (Paralichthys olivaceus) by PCR, histopathological, and immunological techniques. To further understand lymphocystis formation, transcriptome sequencing of skin nodule tissue was performed by using healthy flounder skin as a control. In total, RNA-seq produced 99.36%-99.71% clean reads of raw reads, of which 91.11%-92.89% reads were successfully matched to the flounder genome. The transcriptome data showed good reproducibility between samples, with 3781 up-regulated and 2280 down-regulated differentially expressed genes. GSEA analysis revealed activation of Wnt signaling pathway, Hedgehog signaling pathway, Cell cycle, and Basal cell carcinoma associated with nodule formation. These pathways were analyzed to interact with multiple viral infection and tumor formation pathways. Heat map and protein interaction analysis revealed that these pathways regulated the expression of cell cycle-related genes such as ccnd1 and ccnd2 through key genes including ctnnb1, lef1, tcf3, gli2, and gli3 to promote cell proliferation. Additionally, cGMP-PKG signaling pathway, Calcium signaling pathway, ECM-receptor interaction, and Cytokine-cytokine receptor interaction associated with nodule formation were significantly down-regulated. Among these pathways, tnfsf12, tnfrsf1a, and tnfrsf19, associated with pro-apoptosis, and vdac2, which promotes viral replication by inhibiting apoptosis, were significantly up-regulated. Visual analysis revealed significant down-regulation of cytc, which expresses the pro-apoptotic protein cytochrome C, as well as phb and phb2, which have anti-tumor activity, however, casp3 was significantly up-regulated. Moreover, bcl9, bcl11a, and bcl-xl, which promote cell proliferation and inhibit apoptosis, were significantly upregulated, as were fgfr1, fgfr2, and fgfr3, which are related to tumor formation. Furthermore, RNA-seq data were validated by qRT-PCR, and LCDV copy numbers and expression patterns of focused genes in various tissues were also investigated. These results clarified the pathways and differentially expressed genes associated with lymphocystis nodule development caused by LCDV infection in flounder for the first time, providing a new breakthrough in molecular mechanisms of lymphocystis formation in fish.


Toll-like receptor and innate cytokine responses induced by lactobacilli colonization and human rotavirus infection in gnotobiotic pigs.
Toll-like receptors (TLR) play an important role in the recognition of microbes by host sentinel cells that leads to the subsequent innate and adaptive immune responses. In this study, we evaluated the patterns of TLR2-, TLR3- and TLR9-expressing antigen presenting cells (APCs) in spleen and blood of gnotobiotic (Gn) pigs after colonization with a mixture of two strains of lactic acid bacteria (LAB), Lactobacillus acidophilus and Lactobacillus reuteri or infection with the virulent human rotavirus (HRV) Wa strain. We also assessed the influence of LAB on TLR and serum innate cytokine responses induced by HRV. Distributions of subpopulations of APCs [CD14+/-SWC3+CD11R1- monocytes/macrophages and CD14+/-SWC3+CD11R1+ conventional dendritic cells (cDCs)] were described in our previous report (Zhang, W., Wen, K., Azevedo, M.S., Gonzalez, A.M., Saif, L.J., Li, G., Yousef, A.E., Yuan, L., 2008. Lactic acid bacterial colonization and human rotavirus infection influence distribution and frequencies of monocytes/macrophages and dendritic cells in neonatal gnotobiotic pigs. Vet. Immunol. Immunopathol. 121, pp. 222-231). We demonstrated that LAB induced strong TLR2-expressing APC responses in blood and spleen, HRV induced a TLR3 response in spleen, and TLR9 responses were induced by either HRV (in spleen) or LAB (in blood). LAB and HRV have an additive effect on TLR2- and TLR9-expressing APC responses, consistent with the adjuvant effect of LAB. Overall, the frequencies of TLR-expressing CD14+ APCs were higher than CD14- APCs. LAB enhanced the IFN-gamma and IL-4 responses in serum, but it had a suppressive effect on the TLR3- and TLR9-expressing CD14- APC responses in spleen and the serum IFN-alpha response induced by HRV. These results elucidated the systemic TLR2-, TLR3-, and TLR9-expressing monocyte/macrophage and cDC responses after HRV infection, LAB colonization, and the two combined. Our findings facilitate the understanding of the mechanism of LAB's adjuvant effect on rotavirus vaccines and the diverse innate and adaptive immune responses induced by commensal LAB colonization versus rotavirus infection and the interactions between them.


Synaptotagmin XI as a candidate gene for susceptibility to schizophrenia.
Synaptotagmin XI (Syt11) is a member of the synaptotagmin family, which is localized in cells either in synaptic vesicles or the cellular membrane, and is known to act as a calcium sensor. The Syt11 gene is located on chromosome locus 1q21-q22, which was previously reported as a major susceptibility locus of familial schizophrenia. Here, we present evidence for an association between the number of 33-bp repeats in the promoter region of the Syt11 gene and schizophrenia. We found that the transcriptional activity of the gene is affected by the number of 33-bp repeats, which include an Sp1 binding site, suggesting that the excessive expression of Syt11 can be associated with schizophrenia. Another (single nucleotide) polymorphism in the Syt11 5'UTR region, where the potent transcription factor YY1 can bind, also affects the transcriptional activity of Syt11.


Whole exome sequencing and MicroRNA profiling of lung adenocarcinoma identified risk prediction features for tumors at stage I and its substages.
About 20% of stage I lung adenocarcinoma (LUAD) patients suffer a relapse after surgical resection. While finer substages have been defined and refined in the AJCC staging system, clinical investigations on the tumor molecular landscape are lacking. We performed whole exome sequencing, DNA copy number and microRNA profiling on paired tumor-normal samples from a cohort of 113 treatment-naïve stage I Taiwanese LUAD patients. We searched for molecular features associated with relapse-free survival (RFS) of stage I or its substages and validated the findings with an independent Caucasian LUAD cohort. We found sixteen nonsynonymous mutations harbored at EGFR, KRAS, TP53, CTNNB1 and six other genes associated with poor RFS in a dose-dependent manner via variant allele fraction (VAF). An index, maxVAF, was constructed to quantify the overall mutation load from genes other than EGFR. High maxVAF scores discriminated a small group of high-risk LUAD at stage I (median RFS: 4.5 versus 69.5 months; HR = 10.5, 95% CI = 4.22-26.12, P < 0.001). At the substage level, higher risk was found for patients with high maxVAF or high miR-31; IA (median RFS: 32.1 versus 122.8 months, P = 0.005) and IB (median RFS: 7.1 versus 26.2, P = 0.049). MicroRNAs, miR-182, miR-183 and miR-196a were found correlated with EGFR mutation and poor RFS in stage IB patients. Distinctive features of somatic gene mutation and microRNA expression of stage I LUAD are characterized to complement the survival prognosis by substaging. The findings open up more options for precision management of stage I LUAD patients.


Cardiac function in genetically engineered mice with altered adrenergic receptor signaling.
In disease states such as heart failure, catecholamines released from sympathetic nerve endings and the adrenal medulla play a central role in the adaptive and maladaptive physiological response to altered tissue perfusion. G protein-coupled receptors are importantly involved in myocardial growth and the regulation of contractility. The adrenergic receptors themselves are regulated by a set of specific kinases, termed the G protein-coupled receptor kinases. The study of complex systems in vivo has recently been advanced by the development of transgenic and gene-targeted "knockout" mouse models. Combining transgenic technology with sophisticated physiological measurements of cardiac function is an extremely powerful strategy for studying the regulation of myocardial contractility in normal animals and in models of disease states. The purpose of this review is to summarize current knowledge about the regulation of cardiovascular homeostasis involving signaling pathways through stimulation of adrenergic receptors.


Measurement properties of clinical simulation tests: hypertension and chronic obstructive pulmonary disease.
Reliability and validity of two clinical simulation tests were studied, using a multimethod approach. The instruments were originally tested in a project that compared ability of physicians, nurse practitioners, and public health nurses to provide primary care. Reliability was assessed by comparing test scores of the same subjects on two occasions. Validity was assessed by: 1) comparing test scores of two expert panels and of professional health groups (nurses and physicians) with preprofessional groups (nursing and medical students), 2) comparing test contents with authoritative literature on the disease, and 3) analyzing results of test evaluation by all subjects. Subjects of the original project were compared with those in this study. Both tests were found reliable and valid, corroborating the original project's findings that nurse practitioners and physicians are equally proficient in assessment and treatment of health problems. Findings also lend validity to the tests' developmental model and suggest the usefulness of such tests in nursing and medical education.


Isolation and characterization of heparan sulfate from various murine tissues.
Heparan sulfate (HS), is a proteoglycan (PG) found both in the extracellular matrix and on cell surface. It may represent one of the most biologically important glycoconjugates, playing an essential role in a variety of different events at molecular level. The publication of the mouse genome, and the intensive investigations aimed at understanding the proteome it encodes, has motivated us to initiate studies in mouse glycomics focused on HS. The current study is aimed at determining the quantitative and qualitative organ distribution of HS in mice. HS from brain, eyes, heart, lung, liver, kidney, spleen, intestine and skin was purified from 6-8 week old male and female mice. The recovered yield of HS from these organs is compared with the recovered whole body yield of HS. Structural characterization of the resulting HS relied on disaccharide analysis and (1)H-NMR spectroscopy. Different organs revealed a characteristic HS structure. These data begin to provide a structural understanding of the role of HS in cell-cell interactions, cell signaling and sub-cellular protein trafficking as well as a fundamental understanding of certain aspects of protein-carbohydrate interactions.


Dynamics of social behaviour at parturition in a gregarious ungulate.
Group living is the behavioural response that results when individuals assess the costs vs benefits of sociality, and these trade-offs vary across an animal's life. Here we quantitatively assess how periparturient condition (mother/non-mother) and births affect the dynamics of social interactions of a gregarious ungulate, and how such can help to explain evolutionary hypotheses of the mother-offspring bond. To achieve this we used data of the individual movement of a group of Scottish blackface sheep (Ovis aries) marked with GPS collars and properties of mathematical graphs (networks). Euclidean pair-wise distance between sheep were threshold at different percentiles to determine network links, and these thresholds have a profound effect on the connectivity of the resulting network. Births increased the average pair-wise distance between mothers, and between mothers and non-mothers, with less effect on the distance between non-mothers. Mothers occupied peripheral positions within the flock, more evident following births. Associations between individuals (i.e. network community change) were highly dynamic, though mothers were less likely to change community than non-mothers, especially after births. Births hampered individual communication within the flock (assessed via network closeness centrality), especially in mothers. Overall leadership (lead positioning relative to flock movement) was not associated to reproductive condition, and individual leadership rank was not affected by births. A ten minute GPS acquisition time was adequate to capture complex social dynamics in sheep movement. The results on mother's isolation behaviour support the hypotheses of selection for maternal imprint facilitation, reducing risks to nursing alien offspring, and group/multilevel selection on group formation.


Effects of Anemarrhena asphodeloides on focal ischemic brain injury induced by middle cerebral artery occlusion in rats.
The preventive effect of Anemarrhena asphodeloides Bunge (Liliaceae), a traditional Chinese medicine, on ischemia-reperfusion-induced brain injury was evaluated in the rat brain. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion was continued for 22 h. Water extract of Anemarrhena asphodeloides (WEAA) was orally administered promptly prior to and 2 h after reperfusion. Total infarct volume and edema in the ipsilateral hemispheres of ischemia-reperfusion rats were significantly reduced by treatment with WEAA in a dose-dependent manner (p<0.05). The therapeutic time window of WEAA was 3 h in this ischemia-reperfusion rat model. WEAA also significantly inhibited increased neutrophil infiltration of ischemic brain tissue as estimated by myeloperoxidase (MPO) activity and immunohistochemical analysis. MPO-positive cells were markedly reduced by WEAA administration in striatal and cortical areas. These findings suggest that WEAA plays a crucial protective role in ischemia-induced brain injury, and suggest that WEAA could serve as a lead medicinal herb for the development of neuroprotective agents following transient focal ischemic brain injury.


Urinary excretion of 3,N4-etheno-2'-deoxycytidine in humans as a biomarker of oxidative stress: association with cigarette smoking.
Smokers are known to have elevated levels of lipid peroxidation, a form of oxidative stress. Etheno DNA adduct formation can originate from endogenous lipid peroxidation or from exogenous exposure of carcinogens. Using a modified stable isotope dilution GC/negative ion chemical ionization/MS assay originally developed for urinary 3,N(4)-ethenocytosine (epsilonCyt), the nucleoside 3,N(4)-etheno-2'-deoxycytidine (epsilondCyd) was detected for the first time in human urine. The presence of epsilondCyd in human urine was confirmed by LC/electrospray ionization/tandem MS. Concentrations of epsilondCyd in the 24 h urine samples from healthy individuals not occupationally exposed to industrial chemicals were in the range between 0 and 0.80 nM. A statistically significant correlation was established between cigarette smoking and urinary excretion of epsilondCyd after being adjusted for creatinine (p = 0.004). Furthermore, the urinary total antioxidant capacity was found to correlate inversely with the epsilondCyd levels (r = -0.50, p = 0.02). The results indicate that urinary epsilondCyd may provide a valuable noninvasive biomarker for oxidative DNA damage.


Acute stroke management in the elderly.
Though the proportion of elderly stroke patients is increasing, patients >80 years are often excluded from clinical stroke trials. We reviewed the management of older patients presenting with acute ischemic stroke (AIS) and assessed the safety and efficacy of recombinant tissue plasminogen activator (rtPA) administration in a community-based setting. A retrospective review of patients >80 years (n = 341) admitted to a community stroke center with AIS were compared to their younger counterparts (n = 690) using the stroke center database from April 2003 to December 2005. Parameters that were measured included admission and discharge NIH Stroke Scale (NIHSS), rate of thrombolytic treatment, the frequency and etiology of thrombolytic exclusion criteria and complications from rtPA for the different aged populations. Additional data were collected for Barthel Index at 12 months. A total of 166 patients underwent thrombolysis. Older patients were not delayed in reaching the hospital within 3 h of stroke onset (182/690, 26%, in the <80 cohort vs. 98/341, 29%, in the > or = 80 cohort). Although the overall rates of tPA use were similar in both the young and aged cohort, older patients were less likely to be treated with rtPA because of reasons not listed as exclusion criteria (17% in the <80 cohort vs. 32% in the > or = 80 cohort). The older group did not have an excess risk of intracranial hemorrhage following rtPA infusion despite equivalent NIHSS on admission (13.5 in the <80 cohort vs. 12.4 in the > or = 80 cohort). Both groups showed improvement in NIHSS following thrombolytic treatment with a drop of 7.7 points in the younger age group and 5.6 points in the older group. Elderly patients treated with rtPA had a comparable 12-month modified Barthel Index score to younger cohorts. Early treatment with rtPA in patients >80 years appears to be both safe and efficacious. Treated patients showed improvements both acutely (a decrease in NIHSS at 72 h) and chronically, as shown by a sustained improvement in the Barthel Index. A large number of elderly patients were excluded from rtPA treatment despite arriving within the time frame of treatment for reasons not considered as traditional exclusion criteria. Older patients with AIS can be treated safely with thrombolytic therapy in a community setting. This therapy should not be withheld on the basis of age.


Importance of Physical Qualities for Speed and Change of Direction Ability in Elite Female Soccer Players.
Emmonds, S, Nicholson, G, Beggs, C, Jones, B, and Bissas, A. Importance of physical qualities for speed and change of direction ability in elite female soccer players. J Strength Cond Res 33(6): 1670-1678, 2019-The purpose of this study was to determine the importance of physical qualities for speed and change of direction (CoD) ability in female soccer players. Data were collected on 10 female soccer players who were part of a professional English Women's Super League team. Player assessments included anthropometric (stature and body mass), body composition (dual-energy X-ray absorptiometry), speed (10-m and 20-m sprints), CoD ability (505 agility), aerobic (Yo-Yo Intermittent Recovery Test), lower-body strength (bilateral knee extensions), and power (countermovement jump [CMJ], squat jump [SJ], 30-cm drop jump [DJ]) measures. The relationships between the variables were evaluated using eigenvector analysis and Pearson correlation analysis. Multiple linear regression revealed that the performance variables (10 and 20 m speed, mean 505, and CoD deficit mean) can be predicted with almost 100% accuracy (i.e., adjusted R > 0.999) using various combinations of the predictor variables (DJ height, CMJ height, SJ height, and lean body mass). An increase of 1 SD in DJ height was associated with reductions of -5.636 and -9.082 SD in 10-m and 20-m sprint times. One SD increase in CMJ also results in a reduction of -3.317 and -0.922 SD, respectively, in mean 505 and CoD deficit mean values. This study provides comparative data for professional English female soccer players that can be used by strength and conditioning coaches when monitoring player development and assessing the effectiveness of training programs. Findings highlight the importance of developing reactive strength to improve speed and CoD ability in female soccer players.


Contamination of soil with parasite eggs in Surabaya, Indonesia.
Soil was examined for contamination by parasite eggs in Surabaya Indonesia. Surveys were carried out on three occassion; July, 1993 (dry season), March, 1994 (rainy season), and August, 1994 (dry season). Throughout the study, five species of nematode eggs (Ascaris lumbricoides, Toxocara cati, Trichuris trichiura, Physaloptera sp, Capillaria sp), two species of cestode eggs (Hymenolepis diminuta, Spirometra erinacei), and one species of protozoa oocyst (Isospora felis) were detected. The contamination rate and number of species found from the soil were significantly different in the dry and rainy seasons. In the dry season, the prevalence was 8-20%, with two to four species detected. During the rainy season, this rate was 83% with eight species, suggesting parasite infection to possibly occur mainly in this season. The reason for this seasonal difference may be that, in spite of constant temperature around 27 to 29 degrees C throughout the year, rainfall in the dry season in only a few percent of that of the rainy season. We concluded that parasite eggs die during the dry season owing to dryness of the soil. Contamination of soil with parasite eggs and the number of species found were greater in alley-ways and at communal water supply sites around residential areas than in open-air parks or sandy beaches. The method used in the present study proved extremely effective for ascertaining the actual dynamics of parasite infection in a certain region.


Exploration of potential targets and mechanisms of naringenin in the treatment of nonalcoholic fatty liver disease through network pharmacology.
This study aimed to use network pharmacology to investigate the molecular mechanisms and potential targets of naringenin (NR) for nonalcoholic fatty liver disease (NAFLD) treatment to offer new drug development ideas. The structure and compound information of NR were obtained from PubChem and the traditional Chinese medicine system pharmacology database and analysis platform. The traditional Chinese medicine system pharmacology database and analysis platform Database, Comparative Toxicogenomics Database and Encyclopedia of Traditional Chinese Medicine Database were then used to predict the related targets of NR. Online mendelian inheritance in man, Disgenet, Gene cards, The therapeutic target database and Drug bank were used to screen NAFLD targets, and the intersection analysis was performed with the targets of NR active components to obtain the targets of NR in the treatment of NAFLD. The protein-protein interaction network of therapeutic targets was constructed by protein-protein interaction networks functional enrichment analysis 11.0, and gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis of therapeutic targets was performed by Metascape platform. In this study, 171 NR targets and 1748 potential targets of NAFLD were screened, and 89 crossover targets and 16 core targets were screened and finally obtained. A total of 176 GO items were obtained by GO enrichment analysis (P < .05), including 389 biological process, 6 cell composition and 30 molecular function. A total of 137 signaling pathways were obtained by Kyoto encyclopedia of genes and genomes pathway enrichment and screening (P < .05). The core targets of NR in the treatment of NAFLD are TP53, CASP3, PRKCA, AKT1, RELA, PPARG, NCOA2, CYP1A1, ESR1, MAPK3, STAT3, JAK1, MAPK1, TNF, PPARA and PRKCB. Enrichment analysis showed that NR mainly involved in biological processes such as cellular response to nitrogen compound, regulation of miRNA transcription and negative regulation of miRNA-mediated gene silencing. It regulates Hepatitis B, Lipid and atherosclerosis, cytomegalovirus infection, Hepatitis C, AGE-RAGE signaling pathway in diabetic patients complications and other ways play a role in the treatment of NAFLD. The therapeutic effect of NR on NAFLD has the characteristics of multi-targets and multi-pathways, which provides a preliminary theoretical basis for clinical trials and the development of new drugs.


Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis'.
Vitamin D enhances host protective immune responses to Mycobacterium tuberculosis by suppressing Interferon-gamma (IFN-g) and reducing disease associated inflammation in the host. The objectives of this study were to determine whether vitamin D supplementation to patients with tuberculosis (TB) could influence recovery. Two hundred and fifty nine patients with pulmonary TB were randomized to receive either 600,000 IU of Intramuscular vitamin D3 or placebo for 2 doses. Assessments were performed at 4, 8 and 12 weeks. Early secreted and T cell activated 6 kDa (ESAT6) and Mycobacterium tuberculosis sonicate (MTBs) antigen induced whole blood stimulated IFN-g responses were measured at 0 and 12 weeks. Statistical comparisons between outcome variables at 0 and 12 weeks were performed using Student's t-test and Chi2 tests. After 12 weeks, the vitamin D supplemented arm demonstrated significantly greater mean weight gain (kg)+3.75, (3.16-4.34) versus+2.61 (95% CI 1.99-3.23) p 0.009 and lesser residual disease by chest radiograph; number of zones involved 1.35 v/s 1.82 p 0.004 (95% CI 0.15, 0.79) and 50% or greater reduction in cavity size 106 (89.8%) v/s 111 (94.8%), p 0.035. Vitamin D supplementation led to significant increase in MTBs-induced IFN-g secretion in patients with baseline 'Deficient' 25-hydroxyvitamin D serum levels (p 0.021). Supplementation with high doses of vitamin D accelerated clinical, radiographic improvement in all TB patients and increased host immune activation in patients with baseline 'Deficient' serum vitamin D levels. These results suggest a therapeutic role for vitamin D in the treatment of TB. ClinicalTrials.gov; No. NCT01130311; URL: clinicaltrials.gov.


Isolation gowns as a potential work hazard.
Isolation gowns are used as a barrier to bacterial transmission from patient to provider and vice versa. If an isolation gown is ineffective, the patient and provider have a potential breach of safety and increased infection risk. This study compared the bacterial permeability of differently rated, commonly uses isolation gowns to assess their effectiveness in preventing simulated bacterial transmittance, and thus contamination, from patient to provider. Serial dilutions of Staphylococcus epidermidis in sterile saline were applied to a simulated skin surface. Unrated and Levels 1 through 4 non-sterile isolation gowns contacted the solution, simulating patient contact. Both sides of the contaminated gowns were then cultured on blood agar by rolling a sterile swab across the gown and evenly inoculating the culture plate. Colony counts from inside and outside of the gowns were compared. Separately, S. epidermidis was placed on a sample of each gown and scanning electron microscopy was used to visualize the contaminated gowns' physical structure. Mean bacterial transmittance from outside of the gown (i.e. patient contact side) to inside of the gowns (i.e. provider clothing or skin side) based on gown rating was as follows: unrated: 50.4% (SD 9.0%); Level 1: 39.7% (SD 11.2%); Level 2: 16.3% (SD 10.3%); Level 3: 0.3% (SD 0.8%); Level 4: 0.0% (SD 0.0%). Scanning electron microscope imaging of unrated, Level 1, and Level 2 gowns revealed gown pore sizes much larger than the bacteria. The Welch one-way analysis of variance statistic showed significant difference dependent on gown-level rating. Unrated, Level 1, and Level 2 isolation gowns do not provide effective bacterial isolation barriers when bacteria like S. epidermidis make contact with one side of the gown material. Not studied, but implied, is that unrated and lower rated isolation gowns would be as or even more physically permeable to virus particles, which are much smaller than bacteria.


Clinical studies of psychoorganic syndromes among workers with exposure to solvents.
Exposure to organic solvents is common in industry. In Sweden, patients being evaluated for suspected solvent-related diseases now constitute the largest group of patients seen at many clinics of occupational medicine, largely replacing classical occupational disorders. The findings in 128 consecutive patients with solvent exposure have been reviewed for the period 1978-1981. The duration of exposure was 9 years or more for those with a diagnosis of psychoorganic syndrome (POS). "Incipient" POS was seen after a minimum exposure of 3 years duration. Patients with POS also had an increased frequency of polyneuropathy in comparison to those without any signs of POS. It was not possible to link these abnormalities with particular solvent exposure. Clinical chemistry tests were normal except for liver function tests in a few patients.


Antegrade transseptal coronary angiography: an alternative technique in severe vascular disease.
We report the case of a patient with severe vascular disease in whom retrograde access to the aortic root was not possible because of aortoiliac and axillary vascular disease. Antegrade coronary angiography was performed through the transseptal approach using standard catheters, although several technical difficulties were encountered.


Creating a Telemedicine Network of Specialists in Maternal-Fetal Medicine: A Prospective Cohort Study.
Background: Even before coronavirus disease 2019, integrating telemedicine into routine health care has become increasingly attractive. Evidence regarding the benefits of telemedicine in prenatal care is still inconclusive. As one of the largest sectors of preventive medicine with a relative paucity of specialists in maternal-fetal medicine (MFM), the implementation of telemedicine solutions into prenatal care is promising. Our objective aimed at establishing a telemedicine network of specialists in MFM for interprofessional exchange regarding high-risk pregnancies. Furthermore, the aims were to evaluate the providers' attitude toward the telemedicine solutions and to quantify the number of inpatient appointments that were avoided through interprofessional video consultations. Methods: This prospective trial was part of a larger telemedicine project funded by the European Regional Development Fund. MFM experts were brought together using the ELVI software. A questionnaire was designed for the evaluation of video consultations. The responses were analyzed by the exact McNemar-Bowker test to compare planned procedures before and after video consultation. Results: An interprofessional network of specialists in prenatal ultrasound was established with a total of 140 evaluations for statistical analysis. Interprofessional video communication was viewed favorably by providers. Overall, 47% (33/70) of the scheduled visits were avoided after video consultation. The providers' tendency to refrain from sending their patients to the University Hospital Münster was statistically noticeable (p = 0.048). Conclusions: Interprofessional exchange through video consultation holds great potential in the context of prenatal care. More prospective research is needed to clearly establish the most beneficial standard of care for both patients and providers. Clinical trial registration number: 2019-683-f-S.


Luteolin and its inhibitory effect on tumor growth in systemic malignancies.
Lamy et al have provided interesting data in their recent article in your esteemed journal. Luteolin augments apoptosis in a number of systemic malignancies. Luteolin reduces tumor growth in breast carcinomas. Luteolin mediates this effect by up-regulating the expression of Bax and down-regulating the expression of Bcl-xL. EGFR-induced MAPK activation is also attenuated. As a result there is increased G2/ M phase arrest. These effects have been seen both in vivo as well as in vitro. It also reduces ERα expression and causes inhibition of IGF-1 mediated PI3K-Akt pathway. Luteolin also activates p38 resulting in nuclear translocation of the apoptosis-inducing factor. Simultaneously it also activates ERK. As a result there is increased intra-tumoral apoptosis which is caspase dependent as well as caspase independent.


[A patient with thyroid cancer evaluated according to Response Evaluation Criteria in Solid Tumors during treatment for breast cancer recurrence in hepatic and cervical lymph nodes].
We describe a case of a 69-year-old woman who underwent left breast-preserving surgery and axillary dissection for left-sided breast cancer at 60 years of age. The histopathological diagnosis was papillotubular carcinoma, luminal A (pathological T1N0M0).In the eighth year after surgery, computed tomography (CT) revealed recurrence in the liver and cervical lymph node metastasis. The patient did not respond to 3 months of treatment with letrozole (progressive disease [PD]). Six courses of chemotherapy with epirubicin and cyclophosphamide (EC) were administered. Subsequently, the attending physician was replaced while the patient was receiving paclitaxel( PTX).After 4 courses of treatment with PTX, the liver metastasis disappeared (complete response [CR]).However, the cervical lymph nodes did not shrink (PD).The cytological diagnosis was papillary thyroid cancer with associated cervical lymph node metastasis. Total thyroidectomy and D3b cervical lymph node dissection were performed. The pathological diagnosis was pEx0T1bN1Mx, pStage IVA disease. Replacement of the attending physician is a critical turning point for patients. During chemotherapy or hormone therapy for breast cancer, each organ should be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST).In the case of our patient, thyroid cancer was diagnosed according to RECIST. Cancer specialists should bear in mind that the treatment policy may change dramatically depending on the results of RECIST assessment.


Theoretical and experimental studies on the performances of barbital-imprinted systems.
By using density functional theory, we studied the interaction process between barbital and 2-vinyl-4,6-diamino-1,3,5-triazine in acetonitrile at 333 K. Barbital and 2-vinyl-4,6-diamino-1,3,5-triazine were used as the template and functional monomer, respectively. The molecularly imprinted polymer microspheres containing barbital and 2-vinyl-4,6-diamino-1,3,5-triazine were synthesized through precipitation polymerization. After removing the template molecule barbital, the average diameter of the obtained molecularly imprinted polymers was 1.45 μm. By optimizing the molar ratio of barbital and the 2-vinyl-4,6-diamino-1,3,5-triazine, the resulting molecularly imprinted polymers showed the highest adsorption for the barbital. The analysis of the Scatchard plot revealed that the dissociation constant (Kd ) and apparent maximum adsorption quantity (Qmax ) of the molecularly imprinted polymers were 30.69 mg/L and 8.68 mg/g, respectively. The study of selective adsorption showed that molecularly imprinted polymers exhibited higher selectivity for barbtital than that for 1,3-dimethyl barbituric acid and pentobarbital. Herein, the studies can provide theoretical and experimental references for the barbital-imprinted system.


Early vulnerability in the development of the sense of maleness: Castration depression in the phallic-narcissistic phase.
This paper considers Brenner's (1975, 1979, 1982) modification of Freud's theory that anxiety is the only signal affect. Brenner introduced the notion that castration depressive affect also can trigger psychic conflict, defense, and symptom formation. Clinical material from the first year of treatment of a three-year-old boy who suffered a regression in daytime bladder control is presented. The focus is threefold: First, to show that the often cited but poorly studied symptom of regression in bladder control may be an indicator of the child 's struggle with the three calamities of childhood (object loss, loss of love, and castration); second, to present data that support the importance in early symptom formation of both anxiety and depressive affect tied to the ideation of castration as well as of object loss; third, to suggest that vulnerability to castration depression is a concept more pertinent to the stage presently labeled the phallic-narcissistic phase, rather than to the oedipal phase of development. The discussion addresses the importance of castration depressive affect as a concept in guiding therapeutic intervention. Vulnerability to castration depressive affect is postulated to be more prominent in the phallic-narcissistic phase because phallic self representation is not yet consolidated.


A Multidisciplinary Program Reduces Over 24 Hours of Physical Restraint in Neurological Intensive Care Unit.
Physical restraint (PR) has to be performed in a well-organized, structured, and careful manner. The safety and effectiveness of the PR procedure in clinical practice are crucial to patient care. The aim of this study was to examine the effect in neurological intensive care units of a multidisciplinary PR reduction program on the overall incidence rate of PR, the monthly rate of PR, and the monthly rate of PR of more than and less than 24 hours, respectively, after controlling for associated factors. A before-and-after study design was conducted in three neurological intensive care units (total of 45 beds) of a medical center in northern Taiwan. A multidisciplinary PR reduction program was implemented, with four phases of data collection. Data on the number and duration of PR were extracted from a database. In the first preintervention phase, data on the rate (number or frequency) and duration of PR were collected for 12 months before program implementation. The next three data collection phases were 1 month (introduction), 3 months (intermediate), and 6 months (maintenance) after program implementation. The chi-square test, one-way analysis of variance with Scheffe's post hoc tests, and logistic regression method were used for data analysis. The results showed that PR was used 72.8 mean times per month before program implementation. After implementation, the mean times per month fell to 40 after the first postimplementation month (introduction), 53.3 after 3 months (intermediate), and 36.2 after 6 months (maintenance). Implementation of the PR reduction program resulted in a decreased incidence rate of PR from 6.1% to 3.2% (event/total patient day) and a decrease in the percentage of patients who were restrained for more than 24 hours from 69.6% to 34.1%. The results of the logistic regression model showed that PR of more than 24 hours was significantly less in the postintervention phases: introduction phase (odds ratio [OR] = 0.31), intermediate phase (OR = 0.16), and maintenance phase (OR = 0.18). Moreover, PR of more than 24 hours was significantly higher in patients with endotracheal intubation (OR = 1.51) and nasogastric intubation (OR = 2.16) and with Glasgow Coma Scale scores of 6-8 (OR = 2.36), 9-12 (OR = 2.40), and 13-15 (OR = 2.15). The results support that a multidisciplinary collaborative program has the potential to decrease the incidence of PR in neurological intensive care units. A standardized protocol and policies are essential for healthcare professionals to effectively use PR as well as to effectively improve the quality of care that is provided to intensive care patients.


Universal versus targeted additional contact precautions for multidrug-resistant organism carriage for patients admitted to an intensive care unit.
Although additional contact precautions (ACPs) are routinely used to reduce cross-transmission of multidrug-resistant organisms (MDROs), the relevance of isolation precautions remains debated. We hypothesized that the collection of recognized risk factors for MDRO carriage on intensive care unit (ICU) admission might be helpful to target ACPs without increasing MDRO acquisition during ICU stays, compared with universal ACPs. This is a sequential single-center observational study performed in consecutive patients admitted to a French medical and surgical ICU. During the first 6-month period, screening for MDRO carriage and ACPs were performed in all patients. During the second 6-month period, screening was maintained, but ACP use was guided by the presence of at least 1 defined risk factor for MDRO. During both periods, 33 (10%) and 30 (10%) among 327 and 297 admissions were, respectively, associated with a positive admission MDRO carriage. During both periods, a second screening was performed in 147 (45%) and 127 (43%) patients. Altogether, the rate of acquired MDRO (positive screening or clinical specimen) was similar during both periods (10% [n = 15] and 11.8% [n = 15], respectively; P = .66). The results of our study contribute to support the safety of an isolation-targeted screening policy on ICU admission compared with universal screening and isolation regarding the rate of ICU-acquired MDRO colonization or infection.


Nonaqueous and halide-free route to crystalline BaTiO3, SrTiO3, and (Ba,Sr)TiO3 nanoparticles via a mechanism involving C-C bond formation.
A novel nonaqueous route for the preparation of nanocrystalline BaTiO(3), SrTiO(3), and (Ba,Sr)TiO(3) has been developed. In a simple one-pot reaction process, the elemental alkaline earth metals are directly dissolved in benzyl alcohol at slightly elevated temperatures. After the addition of Ti(O(i)Pr)(4), the reaction mixture is heated to 200 degrees C, resulting in the formation of a white precipitate. XRD measurements prove the exclusive presence of the perovskite phase without any other crystalline byproducts such as BaCO(3) or TiO(2). TEM investigations reveal that the BaTiO(3) nanoparticles are nearly spherical in shape with diameters ranging from 4 to 5 nm. The SrTiO(3) particles display less uniform particle shapes, and the size varies between 5 and 10 nm. Lattice fringes observed in HRTEM measurements further prove the high crystallinity of the nanoparticles. Surprisingly, GC-MS analysis of the reaction solution after hydrothermal treatment shows that hardly any ether formation occurs during the BaTiO(3) synthesis. Instead, the presence of 4-phenyl-2-butanol in stoichiometric amounts gives evidence that the formation mechanism proceeds mainly via a novel pathway involving C-C bond formation between benzyl alcohol and the isopropanolate ligand.


Effects of Regular Treadmill Exercise on a DNA Oxidative-Damage Marker and Total Antioxidant Capacity in Rat Hippocampal Tissue.
Regular exercise can result in changes in the levels of oxidative stress in the hippocampus; however, little attention has been paid to physical-activity-induced neuronal protection to exposure to lead compounds. This study investigated the effects of regular treadmill exercise on a DNA oxidative-damage marker [8-hydroxy-2'-deoxyguanosine (8-OHdG)] and the total antioxidant capacity (TAC) of hippocampal tissue in lead-acetate exposed rats. This study investigated the effects of 8 weeks of regular treadmill exercise on 8-OHdG and the TAC of hippocampal tissue in lead-acetate-exposed rats. Wistar rats were randomly divided into four groups: baseline, sham (control), lead, and exercise+lead. The exercise program involved running on a treadmill with increasing intensity five times a week for 8 weeks. Animals in the lead and exercise+lead groups received lead acetate at 20 mg/kg body weight intraperitoneally three times weekly for 8 weeks. Animals in the sham group received solvent (ethyl oleate) at 30 mg/kg body weight three times weekly for 8 weeks. TAC and 8-OHdG were measured by spectrophotometric and ELISA techniques, respectively. Data were analyzed by ANOVA and Tukey's post-hoc test with a significance cutoff of p≤0.05. The level of 8-OHdG and the TAC were significantly higher and lower, respectively, in the lead group than in the baseline and sham groups (p<0.01). However, the 8-OHdG level and TAC value in hippocampal tissue were significantly decreased and increased, respectively, in the exercise+lead group relative to the lead group (p<0.05). The TAC of hippocampal tissue may be directly associated with neural protection mechanisms of exercise following lead acetate injection, and the beneficial effects of regular exercise in preventing hippocampal neuronal damage could be due to decreased hippocampal oxidative stress such as reflected by a lower 8-OHdG level and increased TAC.


[Cervical lymphoma from the pediatric viewpoint].
On the background of the immunological maturation of the child, the enlargement of the lymphatic organs are discussed according to their occurrence . Space occupying lesions of the anterior and posterior neck triangles are differentiated facing the favoured occurrence of malignous diseases in the posterior neck triangle. Malignous diseases are found in 15 percent of patient with lymph node swelling. The following tumors of the neck are found in children: Thyreoglossus cysts 26,2%, branchiogenic cysts 23,2%, lymphangioma 10,2%, nonspecific lymphadenopathy 9,8%, tuberculous lymphadenitis including cases caused by mycobacterium avium strains 6,7%, neural tumours 4,1%, thyroid tumours 4,1%, lymphoma and Hodgkins disease 7%, other nonmalignous tumours 6,7%, tumours of the parotid gland 1,5%. Important diseases in differential diagnosis of generalized lymphadenopathy are discussed, as well as prognosis and therapeutical implications.


The AURORA of a New Way to Value Myeloid Immunosuppression in Cancer.
Inhibiting myeloid-derived suppressor cells (MDSC) might be the ultimate barrier to break down tumor defenses and recover the preexisting T-cell immunity required to respond to immunotherapy. However, selectively intercepting MDSCs to prove their etiologic role in cancer progression is not an easy task. In this issue of Cancer Research, Yin and colleagues demonstrate unequivocally that the Aurora A kinase inhibitor, alisertib, specifically neutralizes MDSCs and triggers the rapid accrual of cytotoxic T cells, with consequent tumor clearance potentiated by PD-L1 blockade. Translating this approach into the clinic might rescue tumor immunity in immune-desert landscapes.See related article by Yin et al., p. 3431.


Enhancing the validity of foster care follow-up studies through multiple alumni location strategies.
While family-based placement prevention services, family reunification programs, subsidized guardianship, and aggressive adoption programs are reducing the numbers of children spending long periods of time in substitute care, a significant number of America's children will come of age in foster care. Agencies and policymakers should use research and evaluation to assess the effectiveness of foster care in nurturing healthy adults and to explore ways to improve services. Outcome studies that have focused on locating and interviewing young or middle-aged adults emancipated from foster care have been hampered by modest response rates, limiting the field's ability to evaluate the efficacy of foster care programs. This article describes a set of strategies that were used to achieve higher response rates in two recent follow-up studies.


Dealing with paralogy in RADseq data: in silico detection and single nucleotide polymorphism validation in Robinia pseudoacacia L.
The RADseq technology allows researchers to efficiently develop thousands of polymorphic loci across multiple individuals with little or no prior information on the genome. However, many questions remain about the biases inherent to this technology. Notably, sequence misalignments arising from paralogy may affect the development of single nucleotide polymorphism (SNP) markers and the estimation of genetic diversity. We evaluated the impact of putative paralog loci on genetic diversity estimation during the development of SNPs from a RADseq dataset for the nonmodel tree species Robinia pseudoacacia L. We sequenced nine genotypes and analyzed the frequency of putative paralogous RAD loci as a function of both the depth of coverage and the mismatch threshold allowed between loci. Putative paralogy was detected in a very variable number of loci, from 1% to more than 20%, with the depth of coverage having a major influence on the result. Putative paralogy artificially increased the observed degree of polymorphism and resulting estimates of diversity. The choice of the depth of coverage also affected diversity estimation and SNP validation: A low threshold decreased the chances of detecting minor alleles while a high threshold increased allelic dropout. SNP validation was better for the low threshold (4×) than for the high threshold (18×) we tested. Using the strategy developed here, we were able to validate more than 80% of the SNPs tested by means of individual genotyping, resulting in a readily usable set of 330 SNPs, suitable for use in population genetics applications.


Sequential immunophenotypic analysis of mast cells in a case of systemic mast cell disease evolving to a mast cell leukemia.
The immunophenotypic characteristics of both bone marrow (BM) and peripheral blood (PB) mast cells (MC), from a patient suffering from an aggressive systemic mast cell disease (SMCD), were sequentially analyzed by flow cytometry using direct immunofluorescence. Analysis was carried out at diagnosis, during clinical response induced by interferon alfa-2h/prednisone therapy, and later at relapse. Our results show that together with the CD117 and IgE characteristic markers, at diagnosis BM MC showed strong expression of CD11c, CD13, CD29, CD33, CD44, CD45, CD63, and CD71, and they were also positive for CD2, CD22, CD25, and CD54 although at a lower level. PB MC displayed similar immunophenotypic characteristics although they had a lower expression of CD11c, CD25, CD33, CD63, CD69, and CD71 with a higher reactivity for CD117. Unlike BM MC, PB MC were weakly positive for CD41a and CD61. Sequential studies showed decreased numbers of both BM and PB MC during clinical response associated with a higher expression of the CD29 and CD54 adhesion molecules. In turn, clinical relapse was related to increased numbers of PB and BM MC together with lower CD2, CD11c, CD45, and and CD54 expression and a higher reactivity for the CD117 and CD25 antigens. CD2 had become negative at the last follow-up study. In addition, an increased proportion of S-phase MC was observed at relapse. These findings suggest that the assessment of the quantitative expression of cell-adhesion molecules and growth-factor receptors together with cell cycle studies of mast cells could be of value for monitoring therapy and predicting clinical outcome in aggressive SMCD.


Contribution of individual Ebp Pilus subunits of Enterococcus faecalis OG1RF to pilus biogenesis, biofilm formation and urinary tract infection.
The endocarditis and biofilm-associated pilus (Ebp) operon is a component of the core genome of Enterococcus faecalis that has been shown to be important for biofilm formation, adherence to host fibrinogen, collagen and platelets, and in experimental endocarditis and urinary tract infection models. Here, we created single and double deletion mutants of the pilus subunits and sortases; next, by combining western blotting, immunoelectron microscopy, and using ebpR in trans to increase pilus production, we identified EbpA as the tip pilin and EbpB as anchor at the pilus base, the latter attached to cell wall by the housekeeping sortase, SrtA. We also confirmed EbpC and Bps as the major pilin and pilin-specific sortase, respectively, both required for pilus polymerization. Interestingly, pilus length was increased and the number of pili decreased by deleting ebpA, while control overexpression of ebpA in trans restored wild-type levels, suggesting a dual role for EbpA in both initiation and termination of pilus polymerization. We next investigated the contribution of each pilin subunit to biofilm formation and UTI. Significant reduction in biofilm formation was observed with deletion of ebpA or ebpC (P<0.001) while ebpB was found to be dispensable; a similar result was seen in kidney CFUs in experimental UTI (ΔebpA, ΔebpC, P≤0.0093; ΔebpB, non-significant, each vs. OG1RF). Hence, our data provide important structural and functional information about these ubiquitous E. faecalis pili and, based on their demonstrated importance in biofilm and infection, suggest EbpA and EbpC as potential targets for antibody-based therapeutic approaches.


Development of language and arithmetic skills: risk and protective factors. Comparative cross-sectional study.
In a literate society, linguistic/arithmetic performance is highly valued. Based on defined risk factors, strategies for promotion of better performance can be developed. To ascertain the risk and protective factors relating to development of language and arithmetic. Observational comparative cross-sectional study at a public elementary school in Ribeirão Preto (SP), Brazil. A total of 66 children (41% females) attending first to fifth grades participated in this study. They were divided into two groups: G1, children classified as presenting language or arithmetic deficits; G2, average performance. Language (oral and written) and arithmetic skills were assessed through standardized tests. Variables relating to social skills, home environment resources and behavioral problems were assessed through standardized scales. Data on other variables (pre, peri and postnatal complications, maternal variables and others) were collected through interviews. The logistic regression technique with LASSO was used (α = 0.05). Teenage pregnancy and consumption of psychoactive substances during pregnancy or complications during pregnancy were risk factors for performance regarding arithmetic and language. Higher schooling level for the mother was a protective factor in the development of arithmetic and language. Being female and having a history of otitis were risk factors for language. Altered social skills (responsibility and civility) and complaints of inattention were risk factor for arithmetic. Adequate linguistic development was a protective factor for the development of arithmetic. The risk/protective factors included variables relating to the gestational period, mother's age when pregnant, mother's schooling, social skills, behavior and development issues.


DNA damaging and biochemical effects of potassium tetraborate.
Potassium tetraborate (PTB) is a product resulting from the controlled reaction of potassium hydroxide, water and boric acid (BA). It is used in many areas of industry such as disinfectant, detergent and treatment of contact lenses. PTB is one of the boron compounds which is most commonly used in many areas of industry although very limited information is available concerning its toxicity. Therefore, in this study, it is aimed to determine genetic and biochemical effects of PTB in human blood cell cultures (n=4). PTB was added into culture tubes at various concentrations (0-1280 µg/ml). Micronucleus (MN) and chromosomal aberration (CA) tests were performed for genotoxic damage influences estimation. In addition, biochemical parameters (total antioxidant capacity (TAC) and total oxidative status (TOS) were examined to determine oxidative effects. The results indicated that all tested concentrations of PTB were found to be non-genotoxic. In addition, low concentrations (1.25, 2.5 and 5 µg/ml) of PTB caused increases of TAC levels. Furthermore, all concentrations of PTB were not changed the TOS levels in cultured human blood cells. Based on these results, in this study it has been reported for the first time that PTB is not genotoxic and it increases the antioxidant capacity in human peripheral blood lymphocytes.