Colony-stimulating factors and interferon-gamma differentially affect cell surface molecules shared by monocytes and neutrophils.
Monocytes and neutrophils share a common progenitor and perform many similar functions, as reflected in the expression of several shared membrane molecules. We show here that such molecules can be independently regulated by the cytokines interferon-gamma (IFN-gamma) and the colony-stimulating factors (CSF) in the context of the cell type on which they are present. Thus, IFN-gamma causes neutrophils to express the high-affinity receptor for IgG, Fc gamma RI, which has been considered to be a monocyte-specific receptor. Although neutrophil Fc gamma RI never reaches the levels present on monocytes, it is induced more rapidly and by lower amounts of IFN-gamma than monocyte Fc gamma RI. Of the CSF, only macrophage (M) CSF has an effect which is to cause a decrease in expression of monocyte Fc gamma RI. Secondly, after culture monocytes express Fc gamma RIII which is constitutively expressed by neutrophils. Although neutrophil Fc gamma RIII can be readily modulated by IFN-gamma, granulocyte (G) CSF and granulocyte-macrophage (GM) CSF, these cytokines do not alter the low levels of monocyte Fc gamma RIII. Thirdly, expression of the gp55 protein recognized by CD14 monoclonal antibodies is decreased after exposure of monocytes to IFN-gamma. Neutrophils express low levels of CD14 and, in this case, IFN-gamma causes an increase in the CD14 antigen on these cells. Of all the molecules investigated, only HLA class II is confined to monocytes, with increases in expression induced by IFN-gamma but not by the CSF.


Comparative pharmacokinetics of caffeine in young and elderly men.
The pharmacokinetic behavior of caffeine was compared in a group of eight healthy young men aged 20.5 +/- 2.0 years (mean +/- SD), and in a group of eight healthy, elderly men aged 71.2 +/- 3.9 years. Each subject was given a 5 mg/kg dose of caffeine as either an aqueous oral solution or an intravenous infusion over 30 min using a randomized crossover design. Plasma and urine samples were collected for 24 hr following each dose and analyzed for caffeine content using high-performance liquid chromatography. The peak times (tmax), peak concentrations (Cmax), and the percentage of the peroral dose systemically available, F(%), were essentially identical in both age groups, indicating that caffeine was absorbed rapidly and completely after peroral administration. These results also indicated that the first-pass metabolism observed in rats following the peroral administration of caffeine does not occur in either human group studied here. The elimination of caffeine during its terminal disposition phase was log-linear. Several between-group comparisons of other pharmacokinetic parameters were made. Although the average elimination rate constant was greater in the elderly, the difference did not reach statistical significance, possibly because of the considerable intersubject variability in the elimination rate of caffeine, with half-lives ranging from 2.27 to 9.87 hr. The average apparent volume of distribution was significantly lower in the elderly subjects while the clearances were slightly, but not significantly, larger in the elderly subjects. It appears that most aspects of the pharmacokinetic behavior of caffeine are very similar in young and elderly men.


Anti-platelet activity of panaxatriol saponins is mediated by suppression of intracellular calcium mobilization and ERK2/p38 activation.
Increased platelet aggregation is implicated in the pathogenesis of ischemic stroke and anti-platelet strategy may contribute to its therapy. Panaxatriol saponin (PTS), the main components extracted from Panax notoginseng, has been shown to be efficacious in the prevention and treatment of ischemic stroke in China. The aim of this study is to determine the anti-platelet activity and explore the underlying mechanisms. Inhibitory effect of PTS and its main ginsenosides on agonists-induced platelet aggregation was determined using rabbit or human platelets. Intracellular Ca(2+) concentration ([Ca(2+)]i) mobilization was detected with fura-2/AM probe. MAPKs phosphorylation was determined by Western blotting. Our results showed PTS inhibited the rabbit platelet aggregation induced by various agonists (collagen, thrombin and ADP). The three main ginsenosides (Rg1, Re and R1) existing in PTS also showed anti-platelet activity, while their combination exhibited no synergistic effect on rabbit platelet aggregation. Further study demonstrated that PTS and its main ginsenosides also exhibited inhibitory effect on human platelet aggregation. Mechanism study demonstrated that pre-treatment with PTS inhibited the agonists-induced intracellular calcium mobilization. Moreover, PTS significantly suppressed the activation of both ERK2 and p38 by the agonists via reducing the phosphorylation of ERK2 and p38. We proved that PTS is effective in anti-platelet aggregation, which may, at least in part, be related to the suppression of intracellular calcium mobilization and ERK2/p38 activation. This study may provide one reasonable explanation for the efficacy of PTS on the prevention and treatment of ischemic stroke.


Differential effects of mental load on proximal and distal arm muscle activity.
Work-related upper extremity disorders (WRUEDs) that result from keyboarding tasks are prevalent and costly. Although the precise mechanisms causing the disorder are not yet fully understood, several risk factors have been proposed. These include the repetitive nature of the motor task and the associated sustained static working postures, but also more psychological factors such as mental load. Epidemiological surveys have shown that WRUEDs are more prone to develop in the postural muscles of the neck/shoulder area than in the executive muscles controlling the hand. The present study investigated whether the activation patterns of these two muscle types are differentially affected by an additional mental load during the performance of a repetitive tapping task. Participants tapped various keying patterns with their dominant index finger at two prescribed tempi. Mental load was manipulated by means of an auditory short-term memory task. We recorded the EMG activity of two neck/shoulder muscles (trapezius and deltoid), two upper arm muscles (biceps and triceps), and four forearm muscles (flexor digitorum superficialis, extensor digitorum, extensor carpi radialis longus and extensor carpi ulnaris) and analyzed the kinematics and impact forces of the index finger. The results confirmed that the upper limb has two functions. Specifically, activity of the executive distal musculature was increased during tapping at the higher pace, while the activity of the postural upper limb musculature was elevated due to the memory task. We argue that continuously increased muscular activity can lead to fatigue and thus eventually cause musculoskeletal complaints. The results are discussed with respect to biomechanical adaptation strategies that deal with the consequences of increased noise in the neuromotor system due to enhanced mental processing.


Carotid artery revascularization through a radiated field.
Extracranial carotid stenosis is a complication of external head and neck irradiation. The safety and durability of carotid artery revascularization through a radiated field has been debated. We describe the immediate and long-term results in a series of 27 consecutive patients who received treatment over 12 years. From May 1990 to May 2002, 27 consecutive patients underwent 30 primary carotid artery revascularization procedures. All patients had received previous radiation therapy within a mean interval of 10 years (range, 1-26 years), with average radiation dose of 62 Gy (range, 50-70 Gy). Moderate to severe scarring of the skin or radiation fibrosis was present in three fourths of patients. Thirteen patients (48%) had undergone radical neck dissection, and 2 patients had a permanent tracheotomy. The indications for carotid surgery included high-grade (>70%) symptomatic stenosis in 18 patients (60%) and high-grade asymptomatic stenosis in 12 patients (40%). General anesthesia with systematic shunting was used in 18 patients (60%), and regional anesthesia with selective shunting was used in 12 patients (40%). Operations included standard carotid endarterectomy (n = 20), with patch angioplasty (n = 12) or direct closure (n = 8); carotid interposition bypass grafting (n = 7); and subclavian to carotid bypass grafting (n = 3). Primary closure of the surgical wound was performed in all procedures without any special muscular or skin flaps. All patients were followed up for a mean of 40 months (range, 3-99 months). There was one (3.3%) perioperative death, from massive intracerebral hemorrhage; and 1 patient had a transient ischemic attack. In-hospital complications included neck hematoma in 2 patients, which required surgical drainage in 1 patient. There was neither delayed wound healing nor infection. Twelve patients died during follow-up, of causes not related to treatment. None of the surviving patients had further stroke, and all remained asymptomatic. Follow-up duplex scans showed asymptomatic recurrent stenosis greater than 60% in 3 patients, 2 of whom with stenosis greater than 80% underwent repeat operation. Risk for recurrent stenosis greater than 60% at 18 months was 16.6%. Recurrent stenosis occurred in 2 of these patients after saphenous vein bypass, and in 1 patient after endarterectomy with vein patch angioplasty. The clinical results and sustained freedom from symptoms and stroke over 40-month follow-up suggests that carotid revascularization through a radiated field is a safe and durable procedure in patients at high surgical risk, despite a marked incidence of recurrent stenosis.


Pain model and fuzzy logic patient-controlled analgesia in shock-wave lithotripsy.
Pain control in conscious patients was investigated using a push-button, demand-driven supply of drugs. A fuzzy logic patient-controlled analgesia (PCA) algorithm was compared with a conventional algorithm, for alfentanil administration in extracorporeal shock-wave lithotripsy. The conventional PCA algorithm used an initial dose of 0.25mg, a fixed infusion rate of 60 mg h(-1) and a fixed bolus size of 0.2 mg with a 1 min lockout. The fuzzy logic PCA algorithm used an initial dose of 0.25 mg, a changeable infusion rate and a bolus size of 0.1 or 0.05 mg. The infusion rate was adjusted according to a look-up table that accepted the button-pressing history over the last three lockout intervals. The look-up table was designed using fuzzy logic. The bolus size was adjusted according to the button-pressing history over the past two lockout intervals. Twelve patients were treated using conventional PCA, and thirteen were treated with PCA + fuzzy logic control (FLC). PCA + FLC patients consumed 45% less drug. Also, PCA + FLC patients had a mean delivery/demand ratio of 82%, compared with 60% in conventional PCA. When the pain intensity scale was analysed, PCA + FLC patients had acceptable pain intensity at 62%, compared with 44% in conventional PCA.


Comprehensive genetic diversity and molecular evolutionary analysis of Theileria annulata isolates based on TAMS 1 gene.
Molecular epidemiological studies related to the phylogenetic characterization of Theileria annulata are important in delineating the evolutionary history of the parasite. In the current study, the Theileria annulata (T. annulata) merozoite surface antigen 1 (TAMS 1) gene from 14 bovine isolates of T. annulata originating from semi-arid zone of northern India were amplified and sequenced. TAMS 1 gene sequences (n= 337) reported from 16 countries were subsequently analyzed for haplotype network along with genetic diversity. A total of five haplotypes out of the 14 sequenced isolates and 92 haplotypes out of 337 worldwide sequences are documented in this study. Phylogenetic and molecular evolutionary analyses based on TAMS 1 gene sequences showed that T. annulata is dissipated across different countries and numerous strains are closely linked, even though they belong to different geographical locations. The nucleotide homology between 14 isolates from northern India varied between 91.3 and 100%, whereas it was between 31.5 and 100% when sequences across the globe were compared. Haplotype 14 was recognized as most widely distributed haplotype, with 46 isolates circulating in 10 countries. Globally, negligible genetic distance (FST˂0.15) and very high gene flow (Nm˃1) was found in the five populations of the world (South Asia, East Asia, West Asia, Europe and Africa), supporting the absence of clearly defined subgroups in the phylogenetic analysis. Significant negative values of neutrality tests; Tajima's D (D) and Fu and Li's F (F) provided evidence for recent population expansion through positive selection of advantageous variations.


Guidelines for capsule endoscopy: diagnoses will be missed.
Capsule endoscopy represents a significant advance in the investigation of intestinal disease. National Institute of Health and Clinical Excellence, European Society of Gastrointestinal Endoscopy and American Society for Gastrointestinal Endoscopy guidelines support capsule endoscopy in obscure GI bleeding, Crohn's disease and the evaluation of non-steroidal anti-inflammatory drug side-effects, polyposis syndromes and coeliac disease. To determine whether the application of guidelines leads to missed diagnoses that would have been made if less stringent indications were adopted. Retrospective analysis of 100 consecutive unselected capsule endoscopy examinations at Homerton Hospital, from October 2003 to November 2005. All referrals accepted following traditional investigations. Indications and findings were recorded. Comparison made as to whether diagnoses would have been missed if guidelines had been followed and capsule endoscopy not performed. Among the subjects 37 patients were children and 55 were male. Indications included recurrent bleeding and anaemia, assessment of Crohn's disease, 'others', i.e. assessment of coeliac disease, Peutz-Jehgers syndrome, Blue Rubber Bleb syndrome or non-specific abdominal pain. In patients with coeliac disease, widespread enteropathy was confirmed, with additional diagnoses of delayed gastric emptying and colitis. For those with abdominal pain findings included angiodysplasia, lymphoid hyperplasia and distal small bowel ulcers. Capsule endoscopy in patients with non-conventional indications yielded abnormal pathology, such as ulcers and inflammation. If published guidelines had been followed such diagnoses would have been missed.


Controlled clinical trial of prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission.
We conducted a randomised clinical trial on 211 patients with small-cell lung cancer in complete remission (CR). The aim of this trial was to evaluate the effect of prophylactic cranial irradiation (PCI) on overall survival. Eligible patients were randomly assigned to receive either PCI (100 patients) or no PCI (111 patients). Each centre was allowed to use its own PCI protocol as long as the total dose was within the range of 24-30 Gy and delivered in less than 3 weeks with fractions of 3 Gy or less. The mean follow-up is 5 years. The survival curves do not differ significantly (P = 0.25) between the two groups. The 4-year overall survival rate (95% confidence interval) is 22% [15-32%] in the PCI group versus 16% [10-25%] in the control group. The relative risk of death in the PCI group compared to the control group is 0.84 (95% CI = [0.62-1.13]). The incidence of brain metastasis is lower in the PCI group, but the difference is not statistically significant (P = 0.14). The 4-year cumulative rate of brain metastasis is 44% [32-57%] in the PCI group compared to 51% [38-63%] in the control group. In conclusion, in this study, which had to be closed prematurely, no significant difference was found in terms of the incidence of brain metastases nor in survival.


Electron Attachment and Electron Ionization of Formic Acid Clusters Embedded in Helium Nanodroplets.
We report the results of an experimental study of electron ionization of large helium nanodroplets doped with formic acid (FA). Several homologous series of cluster anions are observed, including [FAn-H]-, undissociated FAn-, and these ions complexed with one or more H2O. Some major features resemble those observed upon sputtering of frozen FA films but they differ significantly from results obtained by electron attachment to bare FA clusters in the gas phase. The FAn- and (H2O)[FAn-H]- series show abrupt onsets above n = 2 and 5, respectively. A prominent resonance in the anion yield occurs at 22.5 eV due to the formation of an intermediate He-*. Also observed are homologous series of [FA-H]- or [FA2-H]- complexed with helium. The cation chemistry is dominated by the production of protonated formic acid clusters, [FAnH]+, but various other homologous cluster ion series are observed as well. Graphical Abstract.


Continuous flow plasma exchange in the treatment of homozygous familial hypercholesterolemia.
We report the clinical and laboratory effects of continuous-flow plasma exchange in two patients suffering from homozygous familial hypercholesterolemia. In one (Case 1) plasmapheresis was performed at fortnightly intervals over a period of 18 months; in the other (Case 2) the necessity for surgical relief of an associated supravalvular aortic stenosis resulted in premature termination of the trial. The plasma cholesterol levels in both patients fell by 35 per cent from the mean before study in the course of treatment. In Case 1 this was associated with marked regression of the patient's xanthomas, disappearance of the S-T segment depression seen on effort electrocardiograms obtained prior to the introduction of plasmapheresis, possible widening of the stenosis present at the origin of the left anterior descending coronary artery, and a marked increase in exercise tolerance and diminished frequency of anginal attacks. Cessation of cholestyramine and clofibrate administration during this study did not in any way reverse the reduction of plasma cholesterol achieved by means of plasmapheresis combined with drug therapy. We conclude that plasmapheresis has a role to play in the management of patients with homozygous familial hypercholesterolemia.


Complications due to prolonged ventricular fluid pressure recording.
All complications in a consecutive series of 648 patients subjected to prolonged recording of the ventricular fluid pressure (VFP) during 1982-1986 were registered and analysed. The procedure did not cause permanent symptoms or deficits in any case except for one haemorrhagic complication. Definite infections caused by the VFP recording were found in 4.3% of the 540 patients (83%) surviving their disease or lesion, and in 1.9% in non-survivors. These infections were almost exclusively registered in patients treated with prolonged drainage of hemorrhagic ventricular fluid, while definite infections in other patients were found in only 1.3%. Most infections were caused by Staphylococcus epidermidis and all infections could be treated successfully. Infection did not cause or contribute to the lethal outcome in any case. In 60% of the cases with infectious complications laboratory signs of ventriculitis occurred after a surgical revision of the ventriculostomy. The duration of VFP recording was of subordinate importance for the development of infection. In 13 patients (1.9%) during the studied period a reliable VFP recording was not obtained, a fact that points to the need for alternative methods in a minority of patients with elevated intracranial pressure. It is concluded that complications caused by VFP recording can be kept at an acceptably low frequency in patients without haemorrhagic cerebrospinal fluid demanding long-term drainage.


Interference of sex-related factors in the response of liver cells to experimental mitotic stimuli.
Stimulation of liver cell multiplication was obtained under two different experimental conditions. (1) A single injection of casein solution resulted in (a) an identical synchronized mitotic wave response in 10-day old male and female rats and (b) a significantly lower response in adult male rats compared to females, a difference which was reduced by castration of males at birth but essentially maintained if animals were operated when 10 days old. (2) Partial hepatectomy shortly after puberty resulted in active hepatocyte multiplication occurring 3 hr earlier in females were ovariectomized at birth and significantly reduced when they were spayed at a later age. Hepatocytes of castrated females entered actively into S phase 2 hr later than the sham-operated controls. Unilateral ovariectomy on the other hand indicated that during compensatory and/or hypercompensatory activity of the single ovary there was a maximum difference between the male and female rate of [3H]thymidine uptake in liver nuclei 20 hr after hepatectomy. A further kinetic study (t = 25, 30,40, 65, 90 hr) indicated no significant sex-related difference in the number of S phases per 10,000 cells. The DNA content of regenerating versus control livers was comparable in both sexes at t = 22 and 90 hr but higher in females at t = 40 and 65 hr. A possible early postnatal interference of certain hormonal mechanisms in the receptivity to mitotic stimuli is postulated and discussed.


Sono-chemical synthesis of cellulose nanocrystals from wood sawdust using Acid hydrolysis.
Cellulose nanocrystal (CNC) is a unique material obtained from naturally occurring cellulose fibers. Owing to their mechanical, optical, chemical, and rheological properties, CNC gained significant interest. Herein, we investigate the potential of commercially non-recyclable wood waste, in particular, sawdust as a new resource for CNC. Isolation of CNC from sawdust was conducted as per acid hydrolysis which induced by ultrasonication technique. Thus, sawdust after being alkali delignified prior sodium chlorite bleaching, was subjected to sulfuric acid with concentration of 65% (w/w) at 60°C for 60min. After complete reaction, CNC were collected by centrifugation followed by dialyzing against water and finally dried via using lyophilization technique. The CNC yield attained values of 15% from purified sawdust. Acid hydrolysis mechanism exactly referred that, the amorphous regions along with thinner as well as shorter crystallites spreaded throughout the cellulose structure are digested by the acid leaving CNC suspension. The latter was freeze-dried to produce CNC powder. A thorough investigation pertaining to nanostructural characteristics of CNC was performed. These characteristics were monitored using TEM, SEM, AFM, XRD and FTIR spectra for following the changes in functionality. Based on the results obtained, the combination of sonication and chemical treatment was great effective in extraction of CNC with the average dimensions (diameter×length) of 35.2±7.4nm×238.7±81.2nm as confirmed from TEM. Whilst, the XRD study confirmed the crystal structure of CNC is obeyed cellulose type I with crystallinity index ∼90%. Cellulose nanocrystals are nominated as the best candidate within the range studied in the area of reinforcement by virtue of their salient textural features.


Enhancement of maturity of moral judgment by parent education.
Relationships between maturity of moral judgment of parents, role-taking opportunities in the home, roletaking ability in children and maturity of children's moral judgment were studied. A parent intervention program designed to increase role-taking opportunities in the home thought to lead to an increase in the maturity of moral judgment of children was utilized. Suggestive evidence for the claim that it is possible to accelerate rates of moral maturity of children through intervening indirectly to train their parents was found. Significant relationships were also found between maturity of moral judgment in children and role-taking AND OPPORTUNITIES FOR role-taking in the home. Maturity of moral judgment of parents was not found to be significantly related to maturity of moral judgment of their children.


Skeletal and dentoalveolar modifications in adults with different sagittal facial patterns after personalized miniscrew-assisted rapid palatal expansion: A prospective cone-beam computed tomography study.
This study aimed to compare the skeletal and dental modifications in adults with different sagittal facial patterns by a personalized miniscrew-assisted rapid palatal expander (pMARPE). Forty subjects (aged 18-28 years; 15 females and 25 males) with maxillary transverse deficiency were assigned to 1 of 3 groups (Class I, II, and III relationship) on the basis of their sagittal facial patterns. Each patient was treated with an individually customized expander. A similar expansion protocol was used for all patients. Cone-beam computed tomography scans were obtained before and after expansion. One-way analysis of variance was used to analyze differences among 3 groups in skeletal, dentoalveolar, and periodontal changes (P <0.05). The success rates of expansion were higher in patients with a Class I or II relationship than those with a Class III relationship. Patients with a Class I or II relationship had greater changes in the anterior nasal spine and maxillary basal bone widths. A more parallel sutural opening in the anteroposterior direction was seen in those with a Class II relationship. The tipping of the maxillary first molar increased, and the buccal alveolar bone thickness decreased in all groups after expansion, especially in patients with a Class III relationship. The pMARPE effectively split the midpalatal suture among adults. However, midpalatal suture expansion was more difficult, and there were more dentoalveolar side effects and fewer orthopedic effects in patients with a Class III relationship than in those with Class I or II relationships.


Similar effects of cis-diamminedichloroplatinum(II) and cis-diammine-1,1-cyclobutanedicarboxylatoplatinum(II) on sodium-coupled glucose uptake in renal brush-border membrane vesicles.
cis-Diamminedichloroplatinum(II) (cDDP) has been shown to interfere with reabsorption processes in renal tubular epithelia, leading to polyuria, magnesium and sodium wasting and glucosuria. cDDP inhibits the Na+-coupled uptake of methyl-alpha-D-glucopyranoside (MGP) in renal proximal tubular cells in primary culture. cis-Diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (CBDCA) produces tubular injury qualitatively similar to that of cDDP with a reduced severity. CBDCA inhibits Na+-coupled MGP uptake in renal proximal tubular cells in primary culture at concentrations 20- to 30-times higher than those of cDDP. The Na+/glucose cotransport protein possesses sulphydryl groups (SH) essential for its activity. Platinum complexes have strong affinity for SH groups. We compared the direct effects of cDDP (0.04-1.0 mM) and CBDCA (1-30 mM) on Na+-coupled MGP uptake in rabbit renal brush-border membrane (BBM) vesicles. cDDP and CBDCA inhibited Na+-coupled MGP uptake in a concentration-dependent manner, mainly through a decrease in Vmax of the cotransport protein. These effects were associated with platinum binding to BBM and decreases in protein-bound SH groups. CBDCA altered Na+-coupled MGP uptake at concentrations 30-times higher than those of cDDP. When BBM vesicles were preincubated with cDDP or CBDCA, diethyldithiocarbamate (an antidote against cDDP-induced nephrotoxicity) partly restored Na+-coupled MGP uptake and reduced the amount of platinum bound to BBM, but did not restore protein-bound SH groups. These findings strongly suggest that the inhibition of Na+-coupled MGP uptake by cDDP and CBDCA is mainly mediated by direct chemical binding of platinum to essential SH groups of the cotransport protein but may also involve other nucleophilic groups, such as the SCH3 group of methionine residues.


Generation of an iPSC line (SDQLCHi015-A) from peripheral blood mononuclear cells of a patient with mental retardation type 15 carrying c.1007_1011del, p.(Ile336fs) in CUL4B gene.
CUL4B gene mutation can cause intelligence deficiency 15, a syndromic form of X-linked mental retardation characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, speech delay and impairment, tremor and gait ataxia. Here, we generated iPSCs from a Chinese patient with c.1007_1011del (p.(Ile336fs)) in CUL4B gene by reprogramming peripheral blood mononuclear cells with non-integrating vectors. The generated iPSC line (SDQLCHi015-A) expresses pluripotency markers, presents a normal karyotype and is able to differentiate into three germ layers.


Alteration of DNA primase activity by phosphorylation and de-phosphorylation of histone H1.
To investigate the effect of histone H1 on DNA primase activity, partially purified DNA primase from mouse FM3A cells was used. It was found that histone H1 dose dependently inhibited DNA primase. Interestingly phosphorylation of histone H1 reduced the inhibitory activity of the histone. However, de-phosphorylation of the phosphorylated histone H1 resumed the inhibitory activity of DNA primase. These findings lead us to the assumption that phosphorylation and de-phosphorylation of histone may regulate the cell cycle by controlling DNA synthesis through reverse inhibition of DNA primase.


Association of CD44 Gene Polymorphism with Survival of NSCLC and Risk of Bone Metastasis.
Previous studies have reported CD44 expression played an important role in the development and progression of tumor. The aim of study was to investigate whether single nucleotide polymorphisms (SNPs) of CD44 gene were associated with risk of non-small cell lung cancer (NSCLC), survival and occurrence rate of bone metastasis in patients with NSCLC. A total of 234 patients with NSCLC between 2003 and 2010 were enrolled in this study and 468 healthy persons were used as controls. Two polymorphisms, rs13347 and rs187115, in the CD44 gene were genotyped using DNA from blood lymphocytes. For statistical analysis we used the chi-square test, Fisher's exact test, Kaplan-Meier method, and log-rank test. CD44 gene rs13347 polymorphism was not associated with NSCLC risk. For rs187115, the association with NSCLC risk was observed (P<0.001). Allele G carriers had significantly higher occurrence rates of bone metastasis (OR=0.4, 95%CI: 0.20-0.64, P<0.001) and more advanced tumor stage (OR=2.6, 95%CI: 1.50-4.45, P=0.001) compared to carriers of allele A. The survival rates for patients with AA genotype were significantly higher than for patients with the AG+GG genotypes (P<0.001). In multivariate analysis of survival in NSCLC patients, significant predictors were CD44 gene (AG+GG) (RR=0.48, 95%CI: 0.34-0.68, P<0.001), tumor stage (RR=0.45, 95%CI: 0. 0.31-0.65, P<0.001), and bone metastasis (RR=1.52, 95%CI: 1.05-2.21, P=0.027). CD44 gene rs187115 polymorphism is a potential predictive marker of survival in NSCLC patients, and is significantly correlated with bone metastasis and tumor stage.


Attracting Users to Online Health Communities: Analysis of LungCancer.net's Facebook Advertisement Campaign Data.
With growing numbers of adults turning to the internet to get answers for health-related questions, online communities provide platforms with participatory networks to deliver health information and social support. However, to optimize the benefits of these online communities, these platforms must market effectively to attract new members and promote community growth. The aim of this study was to assess the engagement results of Facebook advertisements designed to increase membership in the LungCancer.net online community. In the fall of 2017, a series of 5 weeklong Facebook advertisement campaigns were launched targeting adults over the age of 18 years with an interest in lung cancer to increase opt ins to the LungCancer.net community (ie, the number of people who provided their email to join the site). The advertisements released during this campaign had a sum reach of 91,835 people, and 863 new members opted into the LungCancer.net community by providing their email address. Females aged 55 to 64 years were the largest population reached by the campaign (31,401/91,835; 34.29%), whereas females aged 65 and older were the largest population who opted into the LungCancer.net community (307/863; 35.57%). A total of US $1742 was invested in the Facebook campaigns, and 863 people opted into LungCancer.net, resulting in a cost of US $2.02 per new member. This research demonstrates the feasibility of using Facebook advertising to promote and grow online health communities. More research is needed to compare the effectiveness of various advertising approaches. Public health professionals should consider Facebook campaigns to effectively connect intended audiences to health information and support.


Cell Division: Switching On ECT2 in a Non-Canonical Fashion.
Determining the site of cell cleavage is crucial for cytokinesis and involves precise activation of the RhoGEF ECT2. A new study demonstrates how a non-canonical interaction of ECT2 with centralspindlin underlies cytokinesis in animal cells, solving a mechanistic conundrum.


Patterns and determinants of wood physical and mechanical properties across major tree species in China.
The physical and mechanical properties of wood affect the growth and development of trees, and also act as the main criteria when determining wood usage. Our understanding on patterns and controls of wood physical and mechanical properties could provide benefits for forestry management and bases for wood application and forest tree breeding. However, current studies on wood properties mainly focus on wood density and ignore other wood physical properties. In this study, we established a comprehensive database of wood physical properties across major tree species in China. Based on this database, we explored spatial patterns and driving factors of wood properties across major tree species in China. Our results showed that (i) compared with wood density, air-dried density, tangential shrinkage coefficient and resilience provide more accuracy and higher explanation power when used as the evaluation index of wood physical properties. (ii) Among life form, climatic and edaphic variables, life form is the dominant factor shaping spatial patterns of wood physical properties, climatic factors the next, and edaphic factors have the least effects, suggesting that the effects of climatic factors on spatial variations of wood properties are indirectly induced by their effects on species distribution.


Central mucoepidermoid carcinoma of maxilla with radiographic appearance of mixed radiopaque-radiolucent lesion: a case report.
Mucoepidermoid carcinoma is the most common primary malignancy of the salivary glands. Central mucoepidermoid carcinomas are extremely rare in the jaws. Here we report a case of a 19-year-old central mucoepidermoid carcinoma in a young female patient which was asymptomatic throughout her history and which radiographically simulated a fibro-osseous lesion; both features misled the clinical diagnosis. A radiographic picture of mixed radiopaque-radiolucent appearance in central mucoepidermoid carcinoma is extremely rare. The long duration is also uncommon for a malignant lesion. This case report adds a new dimension to the clinical and radiographic picture a central mucoepidermoid carcinoma can reveal.


Long-Term Stable 1-butyl-3-methylimidazolium Hexafluorophosphate/Ag Metal Composite Membranes for Facilitated Olefin Transport.
For the preparation of long-term stable ionic liquid/Ag nanoparticles composites, we compared the separation performance of 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM+BF4-)/Ag, and 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM+PF6-)/Ag composite membranes with time. Separation performance showed that the BMIM+PF6-/Ag metal composite membrane was more stable than the BMIM+BF4-/Ag metal composite membrane for more than 160 h. These differences in long-term stability in BMIM+PF6-/Ag and BMIM+BF4-/Ag metal composite membranes was attributable to the phase separation between ionic liquid and nanoparticles. In particular, the phase separation between ionic liquid and silver nanoparticles was not observed with time in hydrophobic ionic liquid BMIM+PF6-, confirmed by X-ray photoelectron spectroscopy.


Education in infection control: A need for European certification.
Healthcare-associated infections are common adverse events in acute-care medicine, causing significant morbidity and mortality. There has been a significant increase in the commitment to infection prevention and control (IPC) among European countries in recent years. However, there is still heterogeneity in training opportunities and IPC qualifications. The European Union promotes the harmonization of IPC strategies among member states. The European Centre for Disease Prevention and Control (ECDC)-commissioned Training in Infection Control in Europe project sets the stage for harmonization of IPC activities in Europe by issuing a list of core competencies for IPC professionals. European certification of IPC training and professionals would be the next logical step, which must be achieved by close collaboration between different stakeholders in Europe such as the ECDC, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the European Union of Medical Specialities, and the national IPC societies. Therefore, the ESCMID has launched the new European Committee on Infection Control to take the lead in the implementation of a European (board) certificate for IPC professionals.


Fetal surgery and general anesthesia: a case report and review.
Fetal surgery, in utero, is now a viable option for some congenital conditions due to recent advances in ultrasound and microsurgical technology. Previous reports of anesthesia for such procedures have focused on spinal or epidural conduction techniques. General endotracheal anesthesia may have several advantages in this setting. In addition to maternal anesthesia, general anesthesia can provide fetal neuromuscular block (without direct fetal injection of blocking agents) and uterine relaxation. It may also blunt fetal response to surgical stimulation.


Improved imaging of the carotid artery in the short-axis plane by a mechanical scanning ultrasonic probe.
To image the intima-media complex of the carotid artery in a wider region, a method for measuring cross-sectional images in the arterial short-axis plane is presented. Using the proposed mechanical scanning system for an ultrasonic probe, cross-sectional images of a silicon rubber tube and a human carotid artery are measured in basic experiments and in in vivo experiments, respectively. These experiments show that this method successfully images the short-axis cross sections. Using the method proposed in this article, B-mode images in the short-axis plane can be accurately measured in a wider region than is possible with conventional methods.


Misdiagnosis of persistent left superior vena cava with unroofed coronary sinus as a coronary sinus-type atrial septal defect.
Awareness of persistent left superior vena cava (PLSVC) with unroofed coronary sinus is crucial. Pre- and perioperative evaluation of this association is necessary for surgical plan. Creating an intra-atrial tunnel to divert LSVC to right atrium without obstructing the mitral valve or the pulmonary veins is the safe surgical approach. Unroofed coronary sinus syndrome is a rare congenital heart defect representing less than 1% of all atrial septal defect (ASD) types, and may be associated with persistent left superior vena cava (PLSVC) which may be missed during preoperative diagnosis. Herein, we present a case of a 2-year-old patient who underwent an operation for repair of a coronary sinus-type ASD; however, PLSVC was detected intraoperatively. An antra-atrial tunnel has created to divert the flow of PLSVC into the right atrium along with the repair of the ASD.


Hydrogel-based microsensors for wireless chemical monitoring.
We report fabrication and characterization of a new hydrogel-based microsensor for wireless chemical monitoring. The basic device structure is a high-sensitivity capacitive pressure sensor coupled to a stimuli-sensitive hydrogel that is confined between a stiff porous membrane and a thin glass diaphragm. As small molecules pass through the porous membrane, the hydrogel swells and deflects the diaphragm which is also the movable plate of the variable capacitor in an LC resonator. The resulting change in resonant frequency can be remotely detected by the phase-dip technique. Prior to hydrogel loading, the sensitivity of the pressure sensor to applied air pressure was measured to be 222 kHz/kPa over the range of 41.9-51.1 MHz. With a pH-sensitive hydrogel, the sensor displayed a sensitivity of 1.16 MHz/pH for pH 3.0-6.5, and a response time of 45 minutes.


Electrocoagulation study for the removal of arsenic and chromium from aqueous solution.
This study was undertaken to investigate the removal of arsenic (As) and chromium (Cr) from aqueous solution using electrocoagulation (EC) technique. Batch EC studies were performed using iron electrodes to evaluate the influence of various experimental parameters on the removal of metal ions. The parameters were initial pH (pH(0)), electrolysis time (t), initial concentration (C(0)), electrode gap (g), stirring rate (r) and current density (j). Effect of pH(0) was studied in the range 2.0 to 8.0 while C(0) was varied from 10 to 100 mg/L. As and Cr removal by EC was governed by the chemical dissolution of iron, and the formation of metal-hydrous ferric oxide complexes, which in turn was strongly, influenced by pH(0) and j. Optimum value of pH(0) and j for As and Cr removal were found to be 4.0 and 2.0; and 75 and 50 A/m(2), respectively. Removal efficiency increased with decrease in the value of C(0) and g. The r value of 100 rpm produced sufficient agitation for the proper agglomeration of flocs and optimum removal of ions.


Chemical shift assignments of calmodulin bound to a C-terminal site (residues 1120-1147) in the β-subunit of a retinal cyclic nucleotide-gated channel (CNGB1).
Retinal cyclic nucleotide-gated (CNG) channels consist of two protein subunits (CNGA1 and CNGB1). Calmodulin (CaM) binds to two separate sites within the cytosolic region of CNGB1: CaM binding to an N-terminal site (human CNGB1 residues 565-587, called CaM1) decreases the open probability of CNG channels at elevated Ca2+ levels in dark-adapted photoreceptors, whereas CaM binding to a separate C-terminal site (CNGB1 residues 1120-1147, called CaM2) may increase channel open probability in light activated photoreceptors. We recently reported NMR chemical shift assignments of Ca2+-saturated CaM bound to the CaM1 site of CNGB1 (BMRB no. 51222). Here, we report complete NMR chemical shift assignments of Ca2+-saturated CaM bound to the C-terminal CaM2 site of CNGB1 (BMRB no. 51447).


Immunoglobulin protein and gene transcripts in sea bream (Sparus aurata L.) oocytes.
Cellular mechanisms of Ig transfer to Sparus aurata developing oocytes were analysed. Homologous serum Ig was purified and used to raise the rabbit polyclonal antiserum ORa. Immunohistochemistry revealed an active role of both follicular cells (already at a pre-vitellogenetic stage) and oocytes in the Ig uptake. Early vitellogenetic oocytes (lipid vesicle stages) had ORa staining of outer cortex and oolemma as well as of their follicular cells. In protein yolk granule oocytes, ORa staining was notably found in the pore canals crossing the egg envelope and at the periphery of yolk platelets. A transfer of Ig from the blood to the follicles appears likely. In addition, RT-PCR using specific primers for the constant region of sea bream Ig L chain detected Ig mRNA in released eggs and no signal in post-hatching larvae. These findings show that a significant level of Ig gene transcription in the oocyte and/or a transfer of transcripts may also occur.


Balanced fertigation and improved sustainability of June bearing strawberry cultivated three years in open polytunnel.
Improved precision fertilization by introducing sensors and remote control to secure fruit yield and reduce nutrient leaching in soil culture. We broadcasted before bedding and mulching 50 g m-2 of a multi-mineral fertilizer. Beds had two plant rows 20 cm apart, with plant distance of 25 cm. Experimental design was split plot with three replications and three treatments. Treatments: fertigation in large plots, cultivar in small plots and year. Plant development in the establishing year had no benefit of fertigation in addition to fertilizer given before bedding. When the yield is 3 kg m-2 a nutrient solution of 6 g N m-2 gave highest yield, using 4 g m-2 from two weeks before harvest and during harvest. 'Florence' and 'Sonata' developed well; however, 'Florence' had mildew on fruits in the last cropping year. 'Korona' presented well the first cropping year, but grew small fruits heavily infested by mildew in the last cropping year. Fertilization had effect on fruit yield. It is discussed how a fertilization schedule for the establishment year and cropping years can be adapted to plant development stages. Mildew infestation on fruits was dependent of cultivar and fertilization. Introducing sensors for recording of growth factors and in situ ion-levels of soil water nutrients, proved valuable.


Bovine mastitis in northeastern Brazil: Occurrence of emergent bacteria and their phenotypic and genotypic profile of antimicrobial resistance.
The aim of this study was to identify emergent pathogens associated with bovine mastitis in northeastern Brazil and to characterize them for phenotypic and genotypic resistance to antimicrobials. A total of 321 milk samples from cows with subclinical mastitis were collected, and the isolates obtained in culture were identified using matrix-associated laser desorption-ionization - time of flight mass spectrometry. Phenotypic and genotypic antimicrobial resistance tests were performed. We identified 72 bacteria considered emergent in the study region: Enterococcus faecalis (26.3%; 19/72), Streptococcus agalactiae (22.2%; 16/72), Enterococcus faecium (20.0%; 15/72), Escherichia coli (6.9%; 5/72), 6.9% (5/72) Lactococcus garvieae (6.9%; 5/72), Acinetobacter baumannii (5.5%; 4/72), Bacillus subtilis (1.3%; 1/72), Kocuria marina (1.3%; 1/72), Macrococcus caseolyticus (1.3%; 1/72), Microbacterium resistens (1.3%; 1/72), Micrococcus luteus (1.3%; 1/72), Streptococcus dysgalactiae (1.3%; 1/72), Streptococcus hyovaginalis (1.3%; 1/72) and Streptococcus pluranimalium (1.3%; 1/72). The antibiogram revealed the following resistance profiles: ampicillin (77.7%; 56/72), cefoxitin (69.4%; 50/72), erythromycin (61.1%; 44/72), oxacillin (63.8%; 46/72), penicillin (79.1%; 57/72), tetracycline (63.8%; 46/72), gentamicin (25.0%; 18/72), and vancomycin (20.8%; 15/72). Of the isolates, 83.4% (60/72) showed multiple resistance to antimicrobials. The tetM gene was identified in 43.0% (31/72) of the isolates, followed by tetL (31.9%; 23/72), and blaZ (26.3%; 19/72). 83.4% (60/72) of the isolates presented a multiple antimicrobial resistance index higher than 0,2. Emergent bacteria with zoonotic and multiresistant potential occur in cows with mastitis in northeastern Brazil. It is necessary to monitor the occurrence of these and other bacteria in livestock environments and develop control strategies to prevent their spread.


Osteoma of external auditory canal associated with external auditory canal cholesteatoma and exuberant granulation tissue in mastoid air cell system: a rare association.
Osteoma of EAC is a rare tumour. Cholesteatoma of EAC associated with osteoma is consequence of osteoma of EAC. Its incidence is rare and very few cases have been reported in the literature. Its association with exuberant granulation tissue in the mastoid air cell system without extension of Cholesteatoma into middle ear cleft is even rare. This association has been reported for the first time as evident from review of literature.


[Analysis about the results of allergy screen in 134 cases of allergic rhinitis].
To analyze the results of serum in allergic rhinitis and investigate the specific clinic allergen and serum immunoglobulin E (IgE) levels. Allergy Screen method was used to detect the specific allergen and total serum IgE level of 134 cases of Allergic rhinitis. The dust mite was the most common allergen in inhalation group in 134 cases of allergic rhinitis, the positive rates was 90%; then were donly, feline and scurfy fungus, the positive rates were 16%, 9%. The positive rates of total IgE was 54%. The serum IgE levels between 100 to 200 kU/L, there was 21 cases together, but there existed 7 negative cases. There were 51 cases' IgE levels more than 200 kU/L, the rates was 70.8%, but there still existed 4 negative cases. Allergy screen method can find relevant allergen and provide basis for the prevention and treatment of allergic disease.


Ethanol modifies the actin cytoskeleton in rat pancreatic acinar cells--comparison with effects of CCK.
One of the early events leading to alcoholic pancreatitis seems to be the effect of ethanol on stimulus-secretion coupling. This study examines ethanol-induced modifications of filamentous actin (F-actin) content and localization in acini, the resulting alpha-amylase secretion and the role of protein kinase C (PKC) activity in these processes. Freshly isolated acini were treated with different concentrations of ethanol or cholecystokinin octapeptide (CCK-8) for different periods. F-actin was localized by confocal laser scanning microscopy; its quantity was determined fluorometrically, and the alpha-amylase secretion was measured. Ethanol caused F-actin reorganization resembling the effects of supramaximal CCK-8 stimulation and of direct PKC activation by phorbol-12-myristate-13-acetate. The polyphasic time course of the F-actin content also resembled that under supramaximal CCK-8 stimulation and was counteracted by inhibition of PKC. The PKC inhibitor bisindolylmaleimide I did not increase the ethanol- induced alpha-amylase secretion, but the suboptimally CCK-8-stimulated secretion via high-affinity receptors. Ethanol, like supramaximal CCK-8 concentrations, inhibits acinar secretion by reorganization of the actin cytoskeleton via PKC activation. This effect is suggested to be mediated by low-affinity CCK-A receptors. Together with the ethanol-induced stimulation of early steps of stimulus-secretion coupling, this may be a pancreas-damaging mechanism resembling that in experimental hyperstimulation pancreatitis.


Modulation of spontaneous hippocampal synaptic events with 5-hydroxyindole, 4OH-GTS-21, and rAAV-mediated alpha7 nicotinic receptor gene transfer.
One approach to treatment of negative cognitive effects associated with Alzheimer's disease and schizophrenia may involve activation of neuronal alpha7 nicotinic acetylcholine receptors (nAChRs). We used the alpha7-selective partial agonist 3-(4-hydroxy, 2-methoxy-benzylidene)anabaseine (4OH-GTS-21), the alpha7 modulator 5-hydroxyindole (5-HI), and recombinant adeno-associated virus (rAAV)-mediated alpha7 gene transfer in order to test the hypothesis whether combining these strategies would significantly increase indirect measures of alpha7 nAChR function, including measures of spontaneous synaptic events in CA1 pyramidal cells. 5-HI (1 mM), and 5-HI (1 mM)+4OH-GTS-21 (5 microM) increased the frequency of APV- and NBQX-sensitive currents, while 5-HI+4OH-GTS-21 increased the frequency and amplitude of bicuculline-sensitive currents. Effects on EPSCs were blocked with tetrodotoxin (TTX) (1 microM), but not by methyllycaconitine (MLA) (50 nM). Neither TTX nor MLA reduced the potentiation of IPSC frequencies. However, TTX blocked, and in some cases MLA reduced, the potentiation of IPSC amplitudes. These data suggest that effects of 5-HI+4OH-GTS-21 on EPSC frequency were associated with action potential-dependent transmitter release produced by 5HI, and that potentiation of IPSC amplitudes resulted at least in part, from activation of alpha7 nAChRs. Finally, rAAV-mediated alpha7 gene transfer did not alter the magnitude of effects produced by 5-HI or 5-HI+4OH-GTS-21. Thus, although we previously showed that direct measures of alpha7 nAChR function were enhanced by alpha7 gene transfer, indirect measures of alpha7 nAChRs function were not significantly enhanced by combining alpha7 gene transfer with either agonist activation or positive allosteric modulation of alpha7 nAChRs.


Self-stigma in patients with schizophrenia: a multicentric study from three Latin-America countries.
The aim of this study was to describe the degree of self-stigma in patients with schizophrenia across three Latin-Americans countries (Bolivia, Chile and Peru). The study included 253 outpatients that were assessed using the Internalized Stigma of Mental Illness Scale (ISMI). The results show that 48.7% of patients from Bolivia report high internalized stigma compared to 38.6% from Chile and 28.6% from Peru. There were no statistically significant differences in ISMI mean total scores for country (p = 0.057), however, there were significant differences on two subscales: alienation and social withdrawal for which Bolivia had the highest scores. In conclusion, even though these countries share several common cultural characteristics, there are also some differences between them on patients' self-stigma.


Effect of methacrylic acid beads on the sonic hedgehog signaling pathway and macrophage polarization in a subcutaneous injection mouse model.
Poly(methacrylic acid-co-methyl methacrylate) (MAA) beads promote a vascular regenerative response when used in diabetic wound healing. Previous studies reported that MAA beads modulated the expression of sonic hedgehog (Shh) and inflammation related genes in diabetic wounds. The aim of this work was to follow up on these observations in a subcutaneous injection model to study the host response in the absence of the confounding factors of diabetic wound healing. In this model, MAA beads improved vascularization in healthy mice of both sexes compared to control poly(methyl methacrylate) (MM) beads, with a stronger effect seen in males than females. MAA-induced vessels were perfusable, as evidenced from the CLARITY-processed images. In Shh-Cre-eGFP/Ptch1-LacZ non-diabetic transgenic mice, the increased vessel formation was accompanied by a higher density of cells expressing GFP (Shh) and β-Gal (patched 1, Ptch1) suggesting MAA enhanced the activation of the Shh pathway. Ptch1 is the Shh receptor and a target of the pathway. MAA beads also modulated the inflammatory cell infiltrate in CD1 mice: more neutrophils and more macrophages were noted with MAA relative to MM beads at days 1 and 7, respectively. In addition, MAA beads biased macrophages towards a MHCII-CD206+ ("M2") polarization state. This study suggests that the Shh pathway and an altered inflammatory response are two elements of the complex mechanism whereby MAA-based biomaterials effect vascular regeneration.


Name change among offender patients: an English high security hospital sample.
There is scant literature on change of name among psychiatric patients but a more substantial amount on the use of aliases among offenders. No one to our knowledge has explored name changes among offender patients. This study was undertaken to establish the prevalence of name change among high security hospital patients and to compare those who changed name with those who did not. It was hypothesized that name change would be associated with male gender, repeated offending and a diagnosis of personality disorder. The clinical records of all patients resident in one high security hospital on 31 January 2000 were searched. As all such patients are compulsorily detained, all name changes must be recorded. Any change prior to that date was also noted, together with basic demographic and diagnostic information; supplementary data were obtained from the special hospitals' case register. Seventy-one patients (17%) of the resident population changed names (exclusive of a woman changing her surname on marriage). Name changing was associated with disrupted upbringing. Patients with personality disorder were more likely to change names than those with psychosis, regardless of sex, age or ethnic group. Those with psychosis were more likely to select unusual or symbolic names. On the evidence of previous literature, people from this serious offender patient population were more likely to change names than other psychiatric patients but less likely than non-mentally-disordered offenders. Changes by people with psychosis seemed related to their illness, whereas changes by those with personality disorder might reflect childhood disruptions in rearing patterns.


Evaluation of the reconstruction of brachytherapy implants in three-dimensions from stereo radiographs.
The precision and the accuracy of the stereo-shift method for reconstruction of brachytherapy implants were evaluated. Analysis of shift films was performed by measuring the coordinates of the seeds in an experimental set-up in the laboratory, by manually calculating the coordinates of the seeds from the projection distances on the stereo-shift radiographs, and by using a computer-aided treatment planning system. The resultant reconstructed coordinates agreed well with each other. The uncertainties in precision for the coordinates were expressed as the standard deviation of the measurements. The standard deviation of the computer and manual measurements agreed well with predicted values by an analysis of the random uncertainties in the reconstruction parameters. The uncertainties were within 0.2 mm for the coordinates parallel to the plan of the film and were within 0.4 mm for the coordinate perpendicular to the plane of the shift film. The uncertainties in the accuracy of the reconstruction were compared with the values obtained in clinical practice as well as with the values reported in the literature. Suggestions are made to improve the accuracy.


How I Do It: Hybrid Laparoscopic and Robotic Pancreaticoduodenectomy.
Minimally invasive pancreatic resections remain technically challenging. Distal pancreatectomy has been embraced at multiple centers as an acceptable minimally invasive technique in selected patients. In contrast, minimally invasive pancreaticoduodenectomy has not achieved broad acceptance, partly due to technical challenges. We detail a minimally invasive technique that utilizes both laparoscopic and robotic approaches which capitalizes on the advantages of each. Our early results have encouraged the continued development of this minimally invasive pancreatic surgery program. This hybrid technique may be an approach that is useful for surgeons striving to adopt the advantages of minimally invasive surgery for their patients.


Effects of 5-fluorouracil and mitomycin C on cultured rabbit subconjunctival fibroblasts.
The authors investigated effects of two antimetabolites, 5-fluorouracil (5-FU) and mitomycin C (MMC), on proliferation and motility of cultured rabbit subconjunctival fibroblasts. Both drugs caused dose-dependent inhibition of fibroblast proliferation. These effects were reversible at lower doses (0.33 mg/l of 5-FU, 1.0 X 10(-3) mg/l of MMC) and at an early stage of treatment, but became irreversible at higher doses or after longer treatment times. The degree of growth inhibition reached a plateau after 7 days of treatment. Neither drug altered fibroblast migration in the agarose droplet motility assay or on the intra-cytoplasmic actin distribution by epifluorescent-light microscopy. These results indicate that 5-FU and MMC inhibit subconjunctival fibroblast function predominantly by their effect on cell proliferation rather than on cell motility. The clinical implications of these results may possibly support the use of a much lower total dose of subconjunctival antimetabolite than used in the 5-FU clinical trial.


Protothecosis in Dogs and Cats-New Research Directions.
Protothecosis refers to disease of humans and animals caused by infection with fungus-like, colourless microalgae of the genus Prototheca. Although protothecosis remains an uncommon infection, increasing numbers of human and animal cases are being diagnosed worldwide. This review summarises major new findings in basic science (sequencing analyses of sterol 14α-demethylase (CYP51/ERG11) genes and organelle genomes of Prototheca wickerhamii) to elucidate taxonomic features of this pathogen. Furthermore, this review updates and summarises the clinical features, diagnosis and treatment of protothecosis in dogs and cats. This content of this review is based on information presented at the medical phycology symposium held in the 20th Congress of the International Society for Human and Animal Mycology ( https://www.isham.org/ ).


Selective CO2 Capture and High Proton Conductivity of a Functional Star-of-David Catenane Metal-Organic Framework.
Network structures based on Star-of-David catenanes with multiple superior functionalities have been so far elusive, although numerous topologically interesting networks are synthesized. Here, a metal-organic framework featuring fused Star-of-David catenanes is reported. Two triangular metallacycles with opposite handedness are triply intertwined forming a Star-of-David catenane. Each catenane fuses with its six neighbors to generate a porous twofold intercatenated gyroid framework. The compound possesses exceptional stability and exhibits multiple functionalities including highly selective CO2 capture, high proton conductivity, and coexistence of slow magnetic relaxation and long-range ordering.


Anti-GAD65 reactive peripheral blood mononuclear cells in the pathogenesis of cystic fibrosis related diabetes mellitus.
A role of autoreactive T cells for type 1 diabetes pathogenesis is considered crucial. In our pilot study we addressed if autoreactive mononuclear cells are present also in peripheral blood of patients with other specific forms of diabetes as cystic fibrosis related diabetes (CFRD). Cellular immune responses to a known beta-cell autoantigen (GAD65 and GAD65 derived peptides) were analysed by ELISPOT (IFN-gamma) and by protein microarray analysis in four patients suffering from CFRD, in four cystic fibrosis (CF) patients without diabetes, in eight type 1 diabetes patients (without CF) and in four healthy controls. Response to the autoantigen GAD65 (protein and peptides) was observed in 7/8 patients suffering from CF and in all type 1 diabetes patients. Post-stimulation production of Th1 cytokines (IFN-gamma, TNF-beta) was observed in 2/4 CFRD, 1/4 CF patients and in 7/8 type 1 diabetes patients. All these patients carry prodiabetogenic HLA-DQ genotype. Th2- and Th3 type of cytokine pattern was observed in 2/4 CF patients. Production of IL-8 was observed in the third CFRD as well as in the third CF patient and in 1/8 type 1 diabetes patient and borderline production of this chemokine was also observed in 2/4 healthy controls. No reaction was observed in the other 2/4 healthy controls and in the fourth CFRD patient who carried a strongly protective genotype and did not produce autoantibodies. The most potent peptide of GAD65 was amino acids 509-528. We consider our observations as a sign of a reaction directed against the self-antigen GAD65 that are closely connected to type 1 diabetes. In CF patients who do not develop diabetes autoreactive mechanisms are very probably efficiently suppressed by immune self-tolerance mechanisms. CFRD patients are a heterogenic group. To disclose those who may display features of autoimmune diabetes could have an impact for their therapy and prognosis.


From infinite one-dimensional helix to discrete Cu(II)15 cluster along with in situ S(N)2 ring-cleavage of cis-epoxysuccinic acid: pH-controlled assemblies, crystal structures, and properties.
Two Cu(II) coordination complexes {[Cu(ces)(H(2)O)(2)](H(2)O)(0.5)}(n) (1) and [Cu(15)(dhs)(6)(OH)(6)(H(2)O)(10)](H(2)O)(20) (2) have been synthesized from cis-epoxysuccinic acid (cis-H(2)ces) and Cu(II) perchlorate under different pH conditions (ces = cis-epoxysuccinate and dhs = 2,3-dihydroxysuccinate), and fully characterized by IR spectra, elemental analyses, as well as single crystal and powder X-ray diffraction techniques. Notably, when the reaction was performed at pH above about 7.4, a one-dimensional (1-D) helical chain complex 1 is formed, whereas a neutral isolated Cu(15) nanocluster 2 is generated when the pH value is decreased to the range of about 6.6-7.3, being concomitant with in situ S(N)2 ring-cleavage reaction of cis-H(2)ces to form (2S,3S)- and (2R,3R)-H(4)dhs. Further, extended supramolecular architectures are constructed via secondary interactions in both structures. The magnetic properties of 1 and 2 have also been studied in detail, showing that 1 is an antiferromagnetic helical chain of S = 1/2 spins and 2 possesses an S = 3/2 spin ground state.


Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state.
Sir2 is a NAD(+)-dependent histone deacetylase that controls gene silencing, cell cycle, DNA damage repair, and life span. Prompted by the observation that the [NAD(+)]/[NADH] ratio is subjected to dynamic fluctuations in skeletal muscle, we have tested whether Sir2 regulates muscle gene expression and differentiation. Sir2 forms a complex with the acetyltransferase PCAF and MyoD and, when overexpressed, retards muscle differentiation. Conversely, cells with decreased Sir2 differentiate prematurely. To inhibit myogenesis, Sir2 requires its NAD(+)-dependent deacetylase activity. The [NAD(+)]/[NADH] ratio decreases as muscle cells differentiate, while an increased [NAD(+)]/[NADH] ratio inhibits muscle gene expression. Cells with reduced Sir2 levels are less sensitive to the inhibition imposed by an elevated [NAD(+)]/[NADH] ratio. These results indicate that Sir2 regulates muscle gene expression and differentiation by possibly functioning as a redox sensor. In response to exercise, food intake, and starvation, Sir2 may sense modifications of the redox state and promptly modulate gene expression.


Impaired parasympathetic control of heart rate after myocardial infarction.
We measured the variation in heart rate during deep breathing, a sensitive non-invasive measure of cardiac parasympathetic activity, in 95 patients 3 weeks after myocardial infarction and in 40 asymptomatic healthy controls. The variation in rate was significantly lower (11.6 +/- 6.1 vs 17.6 +/- 7.3 beats/min, P less than 0.001) in patients with myocardial infarction than in controls. Forty-nine patients (52%) and 5 controls (13%) were considered to have diminished (less than or equal to 10 beats/min) variation of rate. The diminution in this variation was not related to the type or location of myocardial infarction, to maximum release of CK-MB or to cardiovascular medication. Our results suggest that impairment of vagal control of heart rate is common after myocardial infarction. The impairment cannot be predicted by any specific feature of the disease.


A case of Stevens-Johnson syndrome possibly induced by amifostine during radiotherapy.
Skin reactions to amifostine are considered to be rare. Here we describe the case of a patient who developed a severe skin eruption (Stevens-Johnson syndrome) during radiotherapy probably due to amifostine. As in most of the patients described so far, the worst lesions were located in the skin areas previously treated with radiotherapy.


Simple advice on lifestyle habits and long-term changes in biomarkers of inflammation and vascular adhesion in healthy middle-aged men.
Lifestyle habits, vascular function and inflammation are components in the development of cardiovascular disease (CVD). We investigated whether simple advice on dietary and exercise habits given (at a single time point) to hypercholesterolemic men affects circulating biomarkers of inflammation and vascular adhesion. In total, 157 men (age 46±5 years) with mild hypercholesterolemia were randomized to four intervention groups, diet (D, n=40), exercise (E, n=39), diet and exercise (DE, n=39) or controls (C, n=39) and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble E-selectin (sE-selectin) were quantified at baseline and after a 6-month intervention period. The intervention applied in this study, that is, simple advice on lifestyle changes given at a single time point, had a modest effect on inflammatory biomarkers and soluble vascular adhesion molecules. The most apparent alterations were found for individuals in group DE, who responded with significant reductions in sICAM-1, -28 (-41 to -14 μg/l) and sE-selectin, -3.6 (-6.9 to -0.3 μg/l) after 6 months. None of the groups had altered their concentrations of sVCAM-1, CRP or IL-6 significantly after the intervention. In all individuals combined, we found changes in apolipoprotein B (apoB) to predict alterations in sICAM-1 (β=0.21) and sE-selectin (β=0.26), independently of changes in inflammation and other adhesion molecules. These observations indicate that even small efforts to improve diet and physical activity can influence biomarkers of vascular function in individuals at increased risk for CVD. ApoB was identified as an important determinant of this improvement, which adds further support to the notion of apoB as a critical target in cardiovascular prevention.


A phased array echoplanar imaging system for fMRI.
A fully parallel, simultaneous sampling phased array receiver system for a clinical echoplanar imaging system is described and evaluated for BOLD activation and relative cerebral blood volume (rCBV) experiments. A 4-coil array curved around the occipital lobe improved SNR by factors of 1.5 in the visual cortex and 3.1 in the visual association cortex relative to a 13-cm diameter surface coil, improving the statistical significance and coverage of visual activation maps. A 4-coil bilateral array increased SNR throughout the head relative to a quadrature head coil by up to a factor of 5 in much of the cortex, with proportional improvement in the SNR of rCBV maps.


Marine fish and benthic biota before the 2019 oil spill: A baseline dataset for monitoring programs and impact assessments at Rio Grande Norte state, Northeastern Brazil.
In 2019 an oil spill spread over more than 4000 km of the Brazilian coastline. Monitoring programs that allow for the evaluation of potential impacts on communities and ecosystems and their recovery through time are needed and rely on baseline information previous to the oil spill. Here we compiled qualitative and quantitative data available from 8 studies on fish and benthic species from different habitats of Rio Grande do Norte (RN) from 2007 to 2018. We assessed the number of species from different locations and compiled information on conservation status and human use. We mapped the study areas and habitats and overlapped them with those affected by the oil spill. The RN state has a high diversity of fish (175 species) and benthic species (285 species), of which more than half of fish (52%) and 2% of benthic species are threatened and 72,8% of fish and 7,9% of benthic species are of commercial interest. Information of most habitats is still poorly known (i.e.majority ofthe available data are from unique and punctual sampling), which may weaken future evaluations of the real impact of the oil spill. Nonetheless, it is possible to design reliable monitoring based on our dataset, persistent contamination and future loss of diversity.


Radial forearm osteocutaneous free flap in maxillofacial and oromandibular reconstructions.
The radial forearm osteocutaneous free flap is an excellent reconstructive modality for oromandibular and maxillofacial reconstruction in certain well-defined circumstances. The initial concern over donor site morbidity and the ability of the bone to reconstruct mandibular defects have led to only a few published series. Retrospective study of the experience of two tertiary medical centers with radial forearm osteocutaneous free flap. Retrospectively, 52 patients were studied who underwent radial forearm osteocutaneous free flap reconstruction for cancer (49 cases) and trauma (3 cases). Bone length and skin paddle harvested, general morbidity (hematoma, wound infection, and dehiscence), recipient site morbidity (nonunion of neomandible, flap failure, and bone or plate exposure), and donor site morbidity (radius bone fracture, plate exposure, and skin graft failure) were reviewed. The average skin paddle size was 55.1 cm (range, 15-112 cm). The average radius bone harvest length was 6.3 cm (range, 2.5-11 cm). Donor site complications included tendon exposure (3 cases), radius bone fracture (1 case), and exposure of the plate (0). Recipient site complications included nonunion of the mandible (4), exposed mandible (1), exposed mandibular plates (2), exposed maxillary plates or bone (0), venous compromise (1), and flap failure (1). Two patients had perioperative deaths. Radial forearm osteocutaneous free flap is a valuable and viable option for oromandibular and maxillofacial reconstruction.


In situfabrication of S-type BiOIxBryheterojunction with metallic Bi for boosting photocatalytic activity for CO2reduction.
Heterojunction construction and morphology control have always been considered effective ways to promote the capability of photocatalysts. In this work, BiOIxBry, S-type heterojunction photocatalysts with metallic Bi nanoparticles, were synthesizedin situusing a solvothermal method, and the influence of reaction temperature (180 °C-220 °C) and dopant doping amount on the catalysts' microscopic morphology, structure, and catalytic properties were researched. Study results revealed the 1:1 BiOIxBrysynthesized at 200 °C exhibited the optimum behavior in CO2reduction. Its catalytic CO2reduction to CH3OH was 932.88μmol gcat-1and C2H5OH was 324.46μmol gcat-1under the analog light source for 8 h, which was approximately 1.92 and 1.49 times higher than that of BiOI-200 °C, respectively. The reinforced catalytic properties are probably attributed to the synergistic effect between metallic Bi nanoparticles and BiOIxBryheterojunction. Thanks to the SPR effect ofin situmetallic Bi, the catalysts' photocarrier separation efficiency is facilitated. Additionally, the heterojunction formation contributes to that trend and more importantly, preserves the charge carriers with strong redox capacity in BiOIxBry, proving product selectivity. We also present a potential electron transfer mechanism involved in the BiOIxBryphotocatalytic CO2reduction based on the characterization analysis and experimental results.


Purification and characterization of two forms of antigen 5 from polybia scutellaris venom.
Two polypeptides from the venom of Polybia scutellaris were purified to homogeneity by RP-HPLC. They differ very slightly in mol. wt (both are about 23,000) and hydrophobicity, and have isoelectric points greater than 9. Amino acid analyzes show close similarity between them and with antigen 5 of vespids from different species. The two polypeptides have an identical N-terminal sequence (18 amino acids) which shows a high degree of homology with those of other vespids. Owing to the fact that the venom of this species is non-allergenic, the data for the mol. wt, isoelectric point, amino acid composition and N-terminal sequence allow us to identify the isolated polypeptides as two forms of antigen 5. Amino acids at positions 5 and 11 in P. scutellaris antigen 5 differ from those of the previously known sequences for antigen 5, suggesting that one or other might be responsible for the lack of allergenicity of the P. scutellaris venom.


Chitosan nanogel aqueous treatment improved blood biochemicals, antioxidant capacity, immune response, immune-related gene expression and infection resistance of Nile tilapia.
Candida albicans is a pathogenic yeast recently associated with diverse diseases in aquaculture. The present study investigated the efficacy of chitosan nanogel (CNG) in ameliorating effects of C. albicans on Nile tilapia (Oreochromis niloticus). Fish were randomly distributed into four groups (control, waterborne CNG at 75 μg/L, intraperitoneally challenged with C. albicans (1.8 × 107 CFU/mL), and waterborne CNG at 75 μg/L + C. albicans at 1.8 × 107 CFU/mL). Results showed that C. albicans infection reduced survival rate (57.5%) and caused marked clinical symptoms in fish among all infected groups. Substantial declines in immunological (complement 3, lysozyme, and immunoglobulin M), protein (total protein and non-albumin protein), and antioxidant (catalase, glutathione peroxidase, and superoxide dismutase) biochemical endpoints were exhibited, The C. albicans infected group also showed marked down-regulation in the expression of immune-related genes, including toll-like receptor 2 (TLR-2), transforming growth factor beta2, tumor necrosis factor alpha, interleukins (IL-1β, IL-6, and IL-10), and antiapoptotic gene (B-cell lymphoma, BCL-2). The expression of the apoptotic gene (Bcl-2 associated X protein, BAX) was up-regulated in fish challenged by C. albicans. The application of waterborne CNG to fish challenged with C. albicans infection improved fish survival (79.5%) and all other measured parameters. The main finding of this work was that CNG is a nanotechnology with potential for preventing degraded health status by C. albicans infection in tilapia, and thus has promise as an intervention in aquaculture settings.


Respiratory tract rather than cutaneous atopic allergy inversely associate with multiple sclerosis: a case-control study.
It has been previously shown that genetic or environmental factors, which promote susceptibility to allergic conditions, prevent the development of Th1-mediated inflammatory disease of multiple sclerosis (MS). To investigate the prediction value of lifetime atopic allergy in development of the future MS, a case-control study was designed. Cases and controls were interviewed between December 2007 and April 2008 and they were asked if they had symptoms or diagnosis of allergies (including respiratory tract allergy, RTA; coetaneous allergy, CA; food/drug allergy, FDA) before MS diagnosis. Of 390 participants (195 controls and 195 cases), 125 healthy controls (64.1%) and 105 cases (53.8%) reported history of at least one type of atopic allergy (P=0.04). A positive history of RTA (OR 0.43; 95% CI 0.28-0.66) or FDA (OR 0.24; 95% CI 0.13-0.43) was inversely associated with the risk of MS. No statistically significant association was found between the history of CA and MS. There is a significant inverse association between RTA and MS that is compatible with a Th1/Th2 imbalance. History of RTA can be considered as a clinically useful risk reducing factor of MS.


Monoclonal antibody BrE-3 participation in a multivariate prognostic model for infiltrating ductal carcinoma of the breast.
Monoclonal antibody (MoAb) BrE-3, an anti-human milk fat globule (HMFG) MoAb, is used here as a novel prognostic indicator for survival and relapse time in patients with infiltrating ductal carcinoma of the breast. A scoring system (4-Score method) was developed to this effect that measured, in a statistically reliable fashion, the level of expression of the epitope for MoAb BrE-3 in the cytoplasm and membranes of breast carcinoma cells in paraffin-embedded sections. In univariate analysis, data obtained by the 4-Score Method as well as data from traditional prognostic indicators (tumor size, axillary node status, and grade of differentiation) were found to be associated with patient survival and relapse. In multivariate analysis, using a Cox proportional hazards regression model, levels of expression of BrE-3 epitope plus tumor size and axillary node status were weighted and combined in an Individual Linear Composite Prognostic Score (ILCPS) that had a high level of association with survival and relapse time in this sample model of patients with infiltrating ductal carcinoma of the breast. This level of association was found to be higher than the level of association for any other combination of traditional or 4-Score method variables. The level of expression of BrE-3 significantly adds to the prognostic capacity of traditional prognostic markers for infiltrating ductal carcinoma of the breast.


Sleep quality and temperament in association with autism spectrum disorder among infants in Japan.
Sleep problems and irritable temperaments are common among infants with autism spectrum disorder (ASD). The prospective association between such sleep problems and irritable temperaments and ASDs needs to be determined for elucidating the mechanism and exploring the future intervention study. Thus, in this study, we investigated whether sleep quality and temperament in 1-month-old infants are associated with the onset of ASD in 3-year-old children. We also assessed its sex-stratified associations. We conducted a longitudinal study using data from 69,751 mothers and infants from a large-cohort study, the Japan Environment and Children's Study. We examined the prospective association between infant sleep quality and temperament at 1 month of age and ASD diagnosis by 3 years of age. Here we show infants with longer daytime sleep have a higher risk of later ASD than those with shorter daytime sleep (risk ratio [RR]: 1.33, 95% confidence interval [CI]: 1.01-1.75). Infants who experienced intense crying have a higher risk of ASD than those who did not (RR: 1.31, 95% CI: 1.00-1.72). There is a difference in sex in the association between a bad mood and later ASD. In particular, female infants experiencing bad moods have a higher risk of ASD than others (RR: 3.59, 95% CI: 1.91-6.75). The study findings provide important information for future intervention to reduce the risk of future ASD.


[69 year-old patient with opaque hemithorax on the right side].
Liposarcomas are the most common sarcomas in adults. Mediastinal occurrence is very rare. We report on a 69 year-old man with a huge tumor in the right pleural cavity leading to a complete atelectasis of the right lung. The tumor could be completely resected. Histology showed a well-differentiated liposarcoma of the mediastinum. One year after resection there was no evidence for local recurrence or metastatic spread.


Nanocellulose/polypyrrole aerogel electrodes with higher conductivity via adding vapor grown nano-carbon fibers as conducting networks for supercapacitor application.
Nanocellulose-based conductive materials have been widely used as supercapacitor electrodes. Herein, electrode materials with higher conductivity were prepared by in situ polymerization of polypyrrole (PPy) on cellulose nanofibrils (CNF) and vapor grown carbon fiber (VGCF) hybrid aerogels. With increase in VGCF content, the conductivities of CNF/VGCF aerogel films and CNF/VGCF/PPy aerogel films increased. The CNF/VGCF2/PPy aerogel films exhibited a maximum value of 11.25 S cm-1, which is beneficial for electron transfer and to reduce interior resistance. In addition, the capacitance of the electrode materials was improved because of synergistic effects between the double-layer capacitance of VGCF and pseudocapacitance of PPy in the CNF/VGCF/PPy aerogels. Therefore, the CNF/VGCF/PPy aerogel electrode showed capacitances of 8.61 F cm-2 at 1 mV s-1 (specific area capacitance) and 678.66 F g-1 at 1.875 mA cm-2 (specific gravimetric capacitance) and retained 91.38% of its initial capacitance after 2000 cycles. Furthermore, an all-solid-state supercapacitor fabricated by the above electrode materials exhibited maximum energy and power densities of 15.08 W h Kg-1, respectively. These electrochemical properties provide great potential for supercapacitors or other electronic devices with good electrochemical properties.


Female infertility is associated with an altered expression of the neurokinin B/neurokinin B receptor and kisspeptin/kisspeptin receptor systems in ovarian granulosa and cumulus cells.
To analyze and compare the expression profile of TAC3, TACR3, KISS1, and KISS1R in mural granulosa and cumulus cells from healthy oocyte donors and patients with different infertility etiologies, including advanced maternal age, endometriosis, and low ovarian response. Genetic association study. Private fertility clinic and public research laboratory. Healthy oocyte donors and infertile women undergoing in vitro fertilization (IVF) treatment. IVF. Gene expression levels of KISS1, KISS1R, TAC3, and TACR3 in human mural granulosa and cumulus cells. Infertile women showed statistically significantly altered expression levels of KISS1 (-2.57 ± 2.30 vs. -1.37 ± 2.11), TAC3 (-1.21 ± 1.40 vs. -1.49 ± 1.98), and TACR3 (-0.77 ± 1.36 vs. -0.03 ± 0.56) when compared with healthy oocyte donors. Advanced maternal age patients, endometriosis patients, and low responders showed specific and altered expression profiles in comparison with oocyte donors. Abnormal expression levels of KISS1/KISS1R and TAC3/TACR3 systems in granulosa cells might be involved in the decreased fertility associated to advanced maternal age, endometriosis, and low ovarian response.


Enhanced Neonatal Brain Responses To Sung Streams Predict Vocabulary Outcomes By Age 18 Months.
Words and melodies are some of the basic elements infants are able to extract early in life from the auditory input. Whether melodic cues contained in songs can facilitate word-form extraction immediately after birth remained unexplored. Here, we provided converging neural and computational evidence of the early benefit of melodies for language acquisition. Twenty-eight neonates were tested on their ability to extract word-forms from continuous flows of sung and spoken syllabic sequences. We found different brain dynamics for sung and spoken streams and observed successful detection of word-form violations in the sung condition only. Furthermore, neonatal brain responses for sung streams predicted expressive vocabulary at 18 months as demonstrated by multiple regression and cross-validation analyses. These findings suggest that early neural individual differences in prosodic speech processing might be a good indicator of later language outcomes and could be considered as a relevant factor in the development of infants' language skills.


Complete response in anaplastic lymphoma kinase-rearranged oncocytic thyroid cancer: A case report and review of literature.
Oncocytic carcinoma of the thyroid is a rare disease, characterized by a poor prognosis and low response rate to radioiodine therapy. Crizotinib is a specific anaplastic lymphoma kinase (ALK) inhibitor, which was initially developed in non-small cell lung cancer. Other solid tumors harboring a translocation in ALK have been described, such as renal carcinoma, thyroid, colorectal, ovarian cancers, and spitzoid melanoma. The research of ALK rearrangements in thyroid tumor is a promising therapeutic track, and treatments need to be explored. We report the case of a 76-year-old woman with a history of multinodular goiter, who was hospitalized for impairment of her general condition. She was diagnosed with metastatic oncocytic thyroid cancer. Synchrone metastases were found: Multiple mediastinal lymphadenopathies, lytic bone lesions and bilateral mammary lumps. Fluorescence in situ hybridization analysis revealed an ALK rearrangement in 61% of cells. No other mutation was found. A tumor board discussion based on molecular characteristics of the tumor suggested initiating a daily treatment by crizotinib, a specific ALK inhibitor. A positron emission tomography scan performed 4 mo after the initiation of crizotinib showed a complete metabolic response. This case highlights an unexpected efficacy of crizotinib in an ALK-rearranged thyroid tumor, and the need of further assessments.


The mismatch negativity in cognitive and clinical neuroscience: theoretical and methodological considerations.
Mismatch negativity (MMN) component of the event-related brain potentials has become popular in cognitive and clinical brain research during the recent years. It is an early response to a violation of an auditory rule such as an infrequent change in the physical feature of a repetitive sound. There is a lot of evidence on the association of the MMN parameters and behavioral discrimination ability, although this relationship is not always straight-forward. Since the MMN reflects sound discrimination accuracy, it can be used for probing how well different groups of individuals perceive sound differences, and how training or remediation affects this ability. In the present review, we first introduce some of the essential MMN findings in probing sound discrimination, memory, and their deficits. Thereafter, issues which need to be taken into account in MMN investigations as well as new improved recording paradigms are discussed.


A new stilbene glycoside from Dryopteris sublaeta.
To study the chemical constituents of Dryopteris sublaeta Ching et Hsu. Fresh plant of Dryopteris sublaeta ching et hsu was extracted twice with boiling water, concentrated to small volume under reduced pressure at 50 degrees C. The concentrated material was partitioned with ether, ethyl acetate, and n-butanol. The fraction of ethyl acetate extract was chromatographed over macroporous adsorption resin (Diaion HP-20) eluted with a mixture of H2O and MeOH in increasing MeOH content. Their fractions from resin were repeatedly chromatographed over Toyopearl HW-40, Sephadex LH-20 and silica gel column chromatography. The compounds were identified on the basis of their physiochemical and spectral data. Four compounds were obtained and identified as 3,5-dihydroxy-stilbene-3-O-neohesperidoside (1), 3,5-dihydroxy-stilbene-3-O-beta-D-glucoside (2), polydotin peceid (3) and 3,5,4'-trihydroxy-bibenzyl-3-O-beta-D-glucoside (4). Compound 1 is a new compound, the others were isolated from Dryopteris for the first time.


The use of 99mTc-DTPA for detection and localization of site of acute gastrointestinal bleeding.
Intravenously injected 99mTc-DTPA was evaluated in 64 patients for its efficiency in detecting and localizing sites of acute upper and lower gastrointestinal (G.I.) bleeding. These studies were correlated with endoscopic and surgical findings. There were 34 bleeders and 30 non bleeders giving a sensitivity of 90%, specificity of 82% and accuracy of 86%. Of these, 49 were upper G.I. studies (stomach 21 and duodenum 28) and 15 were lower G.I. studies (small intestine 8, large bowel 7). Of the 49 upper G.I. studies, 27 showed active bleeding while 22 showed no bleeding at the time of the study resulting in a sensitivity of 87.5%, specificity of 76% and accuracy of 82%. Of the 15 lower G.I. studies, 7 were bleeders while 8 were non bleeders. All the lower G.I. bleeding sites were accurately localized with the 99mTc-DTPA. An incidental finding of these studies was the localization of 99mTc-DTPA in the site of inflammatory and malignant lesions of the G.I. tract. Of the 64 studies, 18 inflammatory and malignant lesions were detected with the IV injected 99mTc-DTPA; 10 were bleeders while 8 were non bleeders. Image subtraction of early from delayed images was helpful to differentiate bleeding from non bleeding cases in this last group of studies.


Cutaneous manifestations of gastrointestinal disease.
Numerous diseases affect the skin and gut simultaneously. The early recognition and treatment of both components is often essential to decrease morbidity and even prevent death precipitated by gastrointestinal crises. A number of the diseases affecting both the skin and gut are discussed, with particular emphasis on recent developments.


Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD.
Neuropsychiatric disorders classically lack defining brain pathologies, but recent work has demonstrated dysregulation at the molecular level, characterized by transcriptomic and epigenetic alterations1-3. In autism spectrum disorder (ASD), this molecular pathology involves the upregulation of microglial, astrocyte and neural-immune genes, the downregulation of synaptic genes, and attenuation of gene-expression gradients in cortex1,2,4-6. However, whether these changes are limited to cortical association regions or are more widespread remains unknown. To address this issue, we performed RNA-sequencing analysis of 725 brain samples spanning 11 cortical areas from 112 post-mortem samples from individuals with ASD and neurotypical controls. We find widespread transcriptomic changes across the cortex in ASD, exhibiting an anterior-to-posterior gradient, with the greatest differences in primary visual cortex, coincident with an attenuation of the typical transcriptomic differences between cortical regions. Single-nucleus RNA-sequencing and methylation profiling demonstrate that this robust molecular signature reflects changes in cell-type-specific gene expression, particularly affecting excitatory neurons and glia. Both rare and common ASD-associated genetic variation converge within a downregulated co-expression module involving synaptic signalling, and common variation alone is enriched within a module of upregulated protein chaperone genes. These results highlight widespread molecular changes across the cerebral cortex in ASD, extending beyond association cortex to broadly involve primary sensory regions.


[Effect of compatibilities and proportions of shuanglong formula on acute myocardial infarction in rats].
To verify the rational of Chinese medicine Shuanglong formula. Rat models of acute myocardial ischemia were induced by hydrochloride isoproterenol. ECG J point change, myocardial infarction area and cellular enzyme (CK, LDH, SOD and MDA) levels were observed and detected to show protective effect of treatment groups. The single drug prescriptions and compatibilities both could improve ECG performance, decrease levels of CK, LDH, SOD and MDA in serum, and reduce a certain myocardial infarct size. The Shuanglong formula at the high dose of 3:7 was proved to be more effective on myocardial ischemia.


Characteristics of Metacordyceps yongmunensis, a New Species from Korea.
Metacordyceps yongmunensis is a newly reported species from Korea, which is very similar to Cordyceps species in morphological characters. It grows on large lepidopteran pupa, and numerous white stromata grow on a single host. Mycelial growth characteristics of M. yongmunensis isolates were studied in different media and at different temperatures. Also, different carbon sources, nitrogen sources, and mineral salts were tested for mycelial growth of M. yongmunensis. Schizophyllum (mushroom) genetics complete medium plus yeast extract, Schizophyllum (mushroom) genetics minimal medium, and Martin's peptone dextrose agar produced longer colony diameters and more compact mycelial density than other media. The optimum temperature for mycelial growth was 25℃. Carbon sources such as sucrose, soluble starch, dextrose, glucose, dextrin, maltose, and fructose showed better mycelial growth, whereas peptone, yeast extract and tryptone resulted in the best mycelial growth of all of the nitrogen sources tested. All of the mineral salts tested showed similar growth as the control, except K2HPO4 which showed longer colony diameter and more compact mycelial density. The compact colonies were white and cottony with a greenish margin. The results showed that M. yongmunensis is an easy fungus to growas it grew from 30 to more than 50 mm in 2 wk.


The proto-oncogene c-kit is expressed in leiomyosarcomas of the uterus.
The proto-oncogene c-kit encodes for a 145-kDa transmembrane tyrosine kinase receptor. Interaction with its ligand, stem cell factor, is essential in the development of hematopoietic stem cells, mast cells, gametocytes, melanocytes, and interstitial cells of Cajal. C-kit expression has been identified in a number of different neoplasms that includes mastocytosis/mast cell leukemia, acute myeloblastic leukemia, seminoma/dysgerminoma, and gastrointestinal stromal tumors. This study examines c-kit expression in uterine endometrial stromal sarcomas, leiomyomas, and leiomyosarcomas using immunohistochemistry. Archival tissue from 38 patients with the uterine mesenchymal tumors (16 leiomyosarcomas, 8 leiomyomas, 11 low-grade endometrial stromal sarcomas, and 3 high-grade endometrial stromal sarcomas) was stained with polyclonal antibody for c-kit. Modified avidin biotin (ABC) immunoperoxidase method was employed for antibody detection. Individual tumors were considered positive if more than 10% of the cells comprising the neoplasm displayed immunoreactive staining. Staining intensity was graded 1+ to 3+ and distribution graded as focal (10-30% of the cells), intermediate (30-60% of the cells), or diffuse (>60% of the cells). C-kit was positive in 12 (75%) of the 16 leiomyosarcomas. The staining was 3+ and diffuse in the majority of the positive tumors. C-kit expression was not detected in any of the 8 leiomyomas. Two of the 3 high-grade endometrial stromal sarcomas displayed c-kit positivity. Staining was diffuse and 3+ in both of these tumors. Expression of c-kit was observed in only 3 of the 11 low-grade endometrial stromal sarcomas. C-kit is expressed in uterine leiomyosarcomas and endometrial stromal sarcomas. Adjunctive diagnostic studies using c-kit may be useful in distinguishing leiomyosarcomas from benign leiomyomas in uterine tumors that offer uncharacteristic features. Furthermore, studies should investigate the prospect of treating these malignant tumors with tyrosine kinase inhibitors.


Radiosynthesis of 6-[C-11]-D-glucose.
Availability of 6-[C-11]-D-glucose will permit positron emission tomography (PET) investigations of glucose utilization derived from the pentose shunt which supports biosynthesis in tissues. The first radiosynthesis of 6-[C-11]-D-glucose is described. As much as 1 mCi of 6-[C-11]-D-glucose, sufficient for animal studies, is obtained from [C-11]CO2 after 100 min with a 16% radiochemical yield (EOB). The radiosynthesis has many attractive features. The method uses [C-11]CH3I and combines a Wittig reaction and a stereoselective OsO4 catalyzed alkene hydroxylation. The OsO4 hydroxylation of the [C-11]-labeled alkene (9) is accomplished in less than 10 min with high stereoselectivity (94:6) in favor of the 6-[C-11]-D-gluco-isomer. HPLC purification (C-18) of the protected labeled sugar removes the undesired 6-[C-11]-L-ido-sugar at an early stage and avoids the use of an expensive low-capacity ion-exchange HPLC column. OsO4, a highly toxic reagent, is removed in the process by adsorption and inactivation on polymer-bound triphenylphosphine.