Human postjunctional alpha-1 and alpha-2 adrenoceptors: differential distribution in arteries of the limbs.
Experiments were performed in order to characterize the post-junctional alpha adrenoceptors that mediate contraction in arteries of human limbs. Blood vessels were obtained from patients undergoing amputation of an extremity for reasons other than vascular disease. Proximal (dorsalis pedis and arcuate arteries of the foot, superficial palmer arch of the hand) and distal (digital arteries of the foot and hand) blood vessels were studied from each limb. The blood vessels were removed within 60 min of amputation and were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution. In proximal and distal arteries, alpha-1 adrenergic blockade with prazosin produced a nonparallel shift in the concentration-effect curve to high compared to low concentrations of the agonist. In contrast, alpha-2 adrenergic blockade with rauwolscine was more effective against responses evoked by low concentrations of norepinephrine. This suggests that the alpha-2 adrenergic component of the response to norepinephrine is a low-maximum effect compared to the alpha-1 adrenergic component. Prazosin was less potent and rauwolscine more potent in distal arteries, compared to proximal arteries which might indicate an increased alpha-2 adrenergic response in distal arteries. The selective alpha-1 adrenergic agonist, phenylephrine, produced similar responses in proximal and distal arteries. However, the selective alpha-2 adrenergic agonist, B-HT 920, caused greater contractile responses in distal arteries compared to proximal arteries. The results suggest that alpha-1 and alpha-2 adrenoceptors are present on the vascular smooth muscle of arteries of human limbs, and that alpha-2 adrenoceptors are more prominent on distal arteries. This may be related to an increased contribution of the distal arteries to thermoregulation.


[Cardiopulmonary exercise capacity before and after heart transplantation].
The aim of heart transplantation is to improve survival and exercise capacity of patients with endstage heart failure. Fifteen patients (1 female, 14 male) with a mean age of 48 years (ranging from 25-62) underwent cardiopulmonary exercise testing (CPX) before heart transplantation. 10/15 patients showed an oxygen uptake of < 4 ml/min/kg (Weber E) at the anaerobic threshold and 5/15 an oxygen uptake between 5 and 8 ml/min/kg (Weber D), so that a severe respectively very severe limitation of exercise capacity was documented before transplantation. Up to now 9/15 patients underwent heart transplantation. Cardiopulmonary exercise test could be repeated in 7 of these 9 patients, 12 up to 22 weeks following operation. Exercise capacity improved from former Weber-class E to class B in 2/5 patients, to class C in 2/5 patients, and to class D in 1/5 patient. Both patients with a preoperative class D improved to class C. Thus, in all cardiac recipients exercise capacity increased, whereas normal values were not reached. The denervation of cardiac allografts leads to a higher heart rate at rest, a delayed increase and diminished slope of exercise response and reduced heart rates at maximal effort. In 17 heart transplant recipients (3 female, 14 male) with a mean age of 53 years (ranging from 25-62), we investigated the exercise capacity with respect to the abnormal rate regulation of the donor heart, which was quantified by comparing the corresponding rate regulation of the remaining part of recipient's atrium driven by the sinus mode.(ABSTRACT TRUNCATED AT 250 WORDS)


Hip-Spine Discordance in Bone Mineral Densities in Patients Undergoing Dual Energy X-Ray Absorptiometry Scan in a Tertiary Care Centre: A Descriptive Cross-sectional Study.
The discordance in the diagnosis of osteoporosis is characterized by the variation in bone mineral density measurements at different skeletal sites. The presence of discordance significantly alters the treatment plan as different treatment is required for different skeletal sites. The aim of this study was to find out the prevalence of hip-spine discordance in bone mineral densities in patients undergoing dual-energy x-ray absorptiometry scans for suspected osteoporosis. A descriptive cross-sectional study was conducted among patients undergoing dual-energy x-ray absorptiometry scans from 1 December 2020 to 30 October 2022. Ethical approval was taken from the Institutional Review Committee (Reference number: IRC-2020-11-18-08). Patients undergoing dual-energy x-ray absorptiometry scans for suspected osteoporosis were included. Patients aged less than 50 years, already diagnosed and under treatment for osteoporosis, and incomplete information about T-scores of hips and spine were excluded. Convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Among 1028 patients, 602 (58.56%) (55.55-61.57, 95% Confidence Interval) had discordance in hip and spine bone mineral densities. The majority of them, 570 (94.68%) were female and 32 (5.71%) were male. Major discordance was observed in 101 (16.77%) patients and minor discordance was observed in 501 (83.22%) patients. The prevalence of discordance in hip and spine bone mineral densities in patients undergoing dual-energy x-ray absorptiometry scans was higher than that reported in other similar studies done in similar settings. bone density; osteoporosis; prevalence.


Cytotoxicity and antitumor activity of platinum (II) complexes of aromatic and cycloalkanecarboxylic acid hydrazides.
New platinum (II) complexes of cyclohexanecarboxylic acid hydrazide (chcah) were synthesized and characterized by elemental analysis, IR, and 1H NMR spectra. Their inhibitory effects on cell growth and macromolecular synthesis of Friend leukemia cells in culture as well as the in vivo antitumor activity towards L1210 leukemia in mice were compared with those of complexes containing differently substituted aromatic acid hydrazides. Some of the complexes exhibited antineoplastic activity. No correlation between the in vivo cytotoxicity and the in vivo antitumor activity was found. However, there was a relationship between the in vitro macromolecular synthesis inhibition profile and the in vivo antineoplastic effect, similar to that of cisplatin. On the other hand, only agents containing one amine ligand were active in vivo. The substitution of the aromatic ring by a cycloalkane residue increased significantly the antitumor effect, with [Pt(NH3)(chcah)Cl2] being the most active compound in this study.


Consumption of argan oil may have an antiatherogenic effect by improving paraoxonase activities and antioxidant status: Intervention study in healthy men.
Due to its high antioxidant and mono- and polyunsaturated fatty acid content virgin argan oil (VAO) could play a beneficial role in cardiovascular prevention. We were therefore interested in determining whether the consumption of VAO could improve plasma paraoxonase (PON1) activities and antioxidant status in healthy men. Sixty young men were included in this interventional study. They were given a controlled diet for 2 weeks as baseline and then received 25 g/day of butter. The group was randomised to two diet group periods of 3 weeks each. The VAO group received 25 ml/day of oil and the extra virgin olive oil (EVO) group received the same quantity of EVO as control group. Plasma PON1 activities, antioxidant vitamins and LDL susceptibility to oxidation were measured. The analysis of the results shows that PON1 activities increase significantly in both groups and that lipoperoxides and conjugated dienes formation decreases significantly in VAO and EVO groups compared to baseline values (P=0.001 and P=0.014, respectively). Vitamin E concentration increases significantly only in VAO group (P=0.007). Susceptibility of LDL to lipid peroxidation shows a significant increase in lag phase and a significant decrease in maximum diene production in VAO (P=0.005) and EVO groups (P=0.041 and P=0.005, respectively). Our findings confirm the beneficial effect of EVO on plasma antioxidant status and show for the first time the same effect for VAO supplementation in man. Thus, VAO offers an additional natural food supplement to reduce cardiovascular risk.


A prognostic biomarker NRG1 promotes U-87 MG glioblastoma cell malignancy by inhibiting autophagy via ERBB2/AKT/mTOR pathway.
Glioblastoma (GBM) is the most common and aggressive primary brain malignancy. Studies have shown that autophagy-related (ATG) genes play important roles in regulating GBM malignancy. However, the mechanism still needs to be fully elucidated. Based on clinical and gene expression information of GBM patients downloaded from The The Cancer Genome Atlas database, Kaplan-Meier, univariate Cox regression, least absolute shrinkage and selection operator regression and multivariate Cox regression were applied to construct a risk signature for GBM prognosis, followed by validation using receiver operating characteristic analysis. Next, Cell Counting Kit-8, wound healing assay, flow cytometry, monodansyl cadaverine autophagy staining assay, immunofluorescence staining and western blot, either in the absence or presence of ERBB2/AKT/mTOR inhibitors, were carried out in GBM U87 cell line to explore molecular pathway underlying GBM malignancy. A three-ATG-gene signature (HIF1A, ITGA3, and NGR1) was constructed for GBM prognosis with the greatest contribution from NRG1. In vitro experiments showed that NRG1 promoted U87 cell migration and proliferation by inhibiting autophagy, and ERBB2/AKT/mTOR is a downstream pathway that mediates the autophagy-inhibitory effects of NRG1. We constructed an ATG gene prognostic model for GBM and demonstrated that NRG1 inhibited autophagy by activating ERBB2/AKT/mTOR, promoting GBM malignancy, thus providing new insights into the molecular contribution of autophagy in GBM malignancy.


Oral Candida carriage and species prevalence in denture stomatitis patients with and without diabetes.
The objective of this study was to assess the oral Candida carriage and species prevalence in denture stomatitis (DS) patients with and without diabetes mellitus (DM). To address the focused question "In patients receiving dentures, how does having diabetes compared to no diabetes influences the carriage and species prevalence of oral Candida?" Indexed databases were explored without time or language restrictions up to and including February 2017. Nine studies were included. In these studies, the number of diabetics ranged between 14 patients and 405 individuals with mean ages ranging between 33 years and 66.4 years. In five studies, the percentage of hyperglycemic patients in the diabetic group ranged from 14.3% to 100%. In one study, all diabetic patients were normoglycemic. Seven studies reported Candida-associated DS to be significantly higher among diabetics than non-diabetics. Candida albicans was the most prevalent species isolated among diabetics and non-diabetics with DS. Denture-wearers with DM are more susceptible to Candida-associated DS as compared to non-diabetics.


Investigation into the Adsorption of Methylene Blue and Methyl Orange by UiO-66-NO2 Nanoparticles.
In this work, the adsorptive removal of methylene blue and methyl orange by UiO-66-NO2 nanoparticles was studied. The influence of pH on the adsorption capacity was assessed. The kinetics of the adsorption process were investigated and compared with pseudo-first-order, pseudo-second-order, Elovich, and intraparticle models. The kinetics of the adsorption fits moderately with the pseudo-first-order, but perfectly fits with pseudo-second-order models, and has a very good fit with the Elovich and intraparticle models. The adsorption isotherms were measured and compared with the Langmuir and Freundlich models. The adsorption capacity of methyl orange (MO) on UiO-66-NO2 nanoparticles (142.9 mg/g) was over three times higher than that of methylene blue (MB) on the nanoparticles (41.7 mg/g). The discrepancy between these capacities was attributed to the presence of the -NO2 functional group, which caused a strong negative mesomeric effect in the metal-organic framework structure.


Correction: Passive particle transport using a transversely propelling polymer "sweeper".
Correction for 'Passive particle transport using a transversely propelling polymer "sweeper"* by K. R. Prathyusha, Soft Matter, 2023, 19, 4001-4010, https://doi.org/10.1039/d2sm01708c.


Epicardial Adipose Tissue Thickness and Carotid Intima-Media Thickness in Hemodialysis Patients.
It is well-known that cardiovascular risk and all-cause mortality is increased in hemodialysis patients. Epicardial fat thickness (EFT), which reflects visceral adiposity, has been suggested as a new cardiometabolic risk factor. The purpose of this study was to investigate EFT in hemodialysis patients. A total of 144 consecutive patients (60 hemodialysis patients and 84 controls) were enrolled into the study, and patients with diabetes mellitus and cardiovascular diseases (CVD) were excluded. EFT was measured on the free wall of the right ventricle at end-diastole from the parasternal long-axis view by standard transthorasic 2D echocardiography. The groups were similar in terms of sex distribution, age, blood pressure, heart rate and frequencies of CAD risk factors including smoking status, family history of CAD and hypertension. There were no significant differences between the hemodialysis patients and controls in 2D echocardiographic parameters, including ejection fraction and biochemical parameters except low-density lipoprotein, high-density lipoprotein and c- reactive protein. Despite having lower body mass index, EFT levels were significantly higher in hemodialysis patients compared to the controls (8.0 ± 2.2 mm vs. 5.8 ± 1.9 mm; p < 0.01). In multivariate linear regression analysis we determined that hemodialysis patient status was found to be an independent predictor for both EFT (β = 0. 700, p = 0.014) and carotid intima-media thickness (CIMT, β = 0. 614, p = 0.047). Hemodialysis patients are independently associated with high EFT and CIMT.


Complete nucleotide sequence and tissue-specific expression of the rat phenylethanolamine N-methyltransferase gene.
The rat phenylethanolamine N-methyltransferase (PNMT) gene was isolated from a genomic library by cross-hybridization with a bovine PNMT cDNA probe. Complete nucleotide sequence analysis of a genomic clone showed that this gene contained three exons and spanned about 2.8 kb in length. There were the acute-phase response element, TATA, SP1, and GRE sequences. The physicochemical properties of rat adrenal PNMT were different from those of the brainstem PNMT. However, northern blot and reverse transcription-polymerase chain reaction analysis showed that the rat PNMT gene may not express the multiple forms of mRNA. These results suggest that the rat PNMT gene might produce a single enzyme protein, whose activity may be differentially modulated by tissue-specific environment in the central and peripheral systems.


Analysis of neutral and basic pharmaceuticals in sewage treatment plants and in recipient rivers using solid phase extraction and liquid chromatography-tandem mass spectrometry detection.
Analytical method was developed which allowed for the detection of four beta blockers (acebutolol, atenolol, metoprolol and sotalol), an antiepileptic drug (carbamazepine) and three fluoroquinolone antibiotics (ciprofloxacin, ofloxacin and norfloxacin) with a single pre-treatment and chromatographic method. The method included an isolation and concentration procedure using solid phase extraction, a separation step using high performance liquid chromatography and a detection procedure applying triple quadrupole mass spectrometry, which was working in the multiple reaction monitoring mode. The method was validated for ground, surface and sewage influent and effluent waters. Due to ion suppression in the electrospray source, the signals monitored for the analytes were less intense in sewage waters compared to ground and surface waters. The limits of quantification were as low as 1 ng L(-1) in ground water and 3.5 ng L(-1) in sewage influent. The method was successfully applied to the determination of the target compounds in raw and treated sewages of three treatment plants in Finland and in their recipient rivers. The results showed that many of the studied compounds pose a moderate to high persistency in sewage treatment as well as in the recipient rivers. The analytical protocol presented may be used for more in-depth studies on the occurrence and fate of these commonly used pharmaceuticals in the sewage treatment plants and in the aquatic environment.


Bending-induced optical loss in random-hole optical fibers.
We present the experimentally determined optical bend loss for random hole optical fibers in the spectral range 1520 to 1570 nm induced by wrapping the optical fiber around a fixed diameter mandrel. The optical losses are compared to those obtained for a single-mode fiber and a multimode fiber using the same bending procedures. The bending induced optical losses in the random hole optical fibers were several orders of magnitude lower than for the single-mode fiber and were about 1 order of magnitude lower than for the multimode fiber.


Postwar changes in the income position of the aged.
Since the war the relative number of aged persons with income from employment has declined, while the proportion with income from social insurance benefits has increased. Despite the fact that social insurance benefits yield a lower average income than do earnings, the averaged aged person's income in 1952 was higher in both current dollars and dollars of stable purchasing power than it was in 1945. The improvement is the result of several factors, including larger earnings by aged workers, increased benefits paid retired workers and their aged survivors under social insurance and related programs higher old-age assistance payments and the rise in the relative number of persons with money income. The growth in the average aged person's income, however, has been at a rate lower than that of the average income of the population as a whole. As a result the average person has had a smaller share in total consumer income in each of the years since 1945 that he had in that year.


Supracrestal bone growth around partially inserted titanium implants in dogs. A pilot study.
8 titanium implants (Nobel Biocare, Göteborg, Sweden) were inserted into edentulous lower premolar areas of 4 dogs so that 6 threads of the implant protruded from the bone crest. Newly-developed perforated dome-shaped titanium space maintainers were fixed to the implant with cover screws. Autogenous bone fragments were placed under the space maintainers. On one side of the arch, the space maintainer was covered with a non resorbable cell occluding barrier. The implant/space maintainers were submerged under coronally positioned flaps. Following a 3-month healing period, there was a mean gain of new bone amounting to 2.5 mm for all specimens. A greater height of bone was found for those sites in which an ePTFE membrane was used; 3.1 mm vs. 1.9 mm (p < 0.05). This study demonstrated the potential of coronal bone growth of the alveolar bone in a protected space around crew implants with exposed treads when placed in the dog.


Psychophysiological effects of self-regulation method: EEG frequency analysis and contingent negative variations.
Experiments were conducted to investigate the psychophysiological effects of self-regulation method (SRM), a newly developed method of self-control, using EEG frequency analysis and contingent negative variations (CNV). The results of the EEG frequency analysis showed that there is a significant increase in the percentage (power) of the theta-band and a significant decrease in the percentage (power) of the beta-band during SRM. Moreover, the results of an identical experiment conducted on subjects in a drowsy state showed that the changes in EEG frequencies during SRM can be differentiated from those of a drowsy state. Furthermore, experiments using CNV showed that there is a significant reduction of CNV amplitude during SRM. Despite the reduced amplitude during SRM, the number of errors in a task to evoke the CNV was reduced significantly without significant delay of reaction time. When an identical experiment was conducted in a drowsy state, CNV amplitude was reduced significantly, but reaction time and errors increased. From these experiments, the state of vigilance during SRM was discussed as a state of 'relaxed alertness'.


Lignocellulosic Biomass: A Sustainable Bioenergy Source for the Future.
Increasing population and industrialization are continuously oppressing the existing energy resources and depleting the global fuel reservoirs. The elevated pollutions from the continuous consumption of non-renewable fossil fuels also seriously contaminating the surrounding environment. The use of alternate energy sources can be an environment-friendly solution to cope these challenges. Among the renewable energy sources biofuels (biomass-derived fuels) can serve as a better alternative to reduce the reliance on non-renewable fossil fuels. Bioethanol is one of the most widely consumed biofuels of today's world. The main objective of this review is to highlight the significance of lignocellulosic biomass as a potential source for the production of biofuels like bioethanol, biodiesel or biogas. We discuss the application of various methods for the bioconversion of lignocellulosic biomass to end products i.e. biofuels. The lignocellulosic biomass must be pretreated to disintegrate lignocellulosic complexes and to expose its chemical components for downstream processes. After pretreatment, the lignocellulosic biomass is then subjected to saccharification either via acidic or enzymatic hydrolysis. Thereafter, the monomeric sugars resulted from hydrolysis step are further processed into biofuel i.e. bioethanol, biodiesel or butanol etc. through the fermentation process. The fermented impure product is then purified through the distillation process to obtain pure biofuel. Renewable energy sources represent the potential fuel alternatives to overcome the global energy crises in a sustainable and eco-friendly manner. In future, biofuels may replenish the conventional non-renewable energy resources due to their renewability and several other advantages. Lignocellulosic biomass offers the most economical biomass to generate biofuels. However, extensive research is required for the commercial production of an efficient integrated biotransformation process for the production of lignocellulose mediated biofuels.


Centrifugal continuous-flow left ventricular assist device in patients with hypertrophic cardiomyopathy: a case series.
Left ventricular assist device (LVAD) therapy has been used primarily in patients with end-stage dilated cardiomyopathy (DCM), and patients with hypertrophic cardiomyopathy (HCM) are generally excluded. We compared outcomes in 3 HCM patients with 36 DCM patients. While HCM patients had smaller left ventricular end-diastolic dimensions, average pump flows for the two groups were similar. All patients had marked improvement in mean pulmonary arterial pressures and cardiac index at 5 months. This analysis shows that patients with end-stage heart failure resulting from HCM do benefit from centrifugal cfLVAD therapy in the short to medium term.


Surgical anatomy of the petrous apex as it relates to the enlarged middle cranial fossa approaches.
This work was designed to study the surgical anatomy of the petrous apex as it relates to the enlarged middle cranial fossa approaches, on 25 temporal bones. In this study we suggest dividing the petrous apex into two topographic areas: an anterior triangular and a posterior quadrangular area with respect to the posterior border of the Gasserian ganglion. Anatomic descriptions endorsed by relevant measurements of these areas are provided in this study.


Improvement of KinectTM sensor capabilities by fusion with laser sensing data using octree.
To enhance sensor capabilities, sensor data readings from different modalities must be fused. The main contribution of this paper is to present a sensor data fusion approach that can reduce Kinect(TM) sensor limitations. This approach involves combining laser with Kinect(TM) sensors. Sensor data is modelled in a 3D environment based on octrees using a probabilistic occupancy estimation. The Bayesian method, which takes into account the uncertainty inherent in the sensor measurements, is used to fuse the sensor information and update the 3D octree map. The sensor fusion yields a significant increase of the field of view of the Kinect(TM) sensor that can be used for robot tasks.


Sphincter preservation with chemoradiation in anal canal carcinoma: abdominoperineal resection in selected cases?
This study contained herein assessed long-term results, toxicity, and prognostic variables following combined modality therapy of patients with International Union Against (Cancer Classification T1-4, N0-3, M0 squamous-cell carcinoma of the anal canal. Between 1985 and 1996, 62 patients completed treatment with combined modality therapy. A median total dose of 50 Gy was given to the primary, perirectal, presacral, and inguinal nodes followed by a local boost in selected cases. 5-Fluorouracil was scheduled as a continuous infusion of 1,000 mg/m2 per 24 hours on days 1 to 5 and 29 to 33 and mitomycin C as a bolus of 10 mg/m2 on days 1 and 29. Routinely processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferating cell nuclear antigen and MIB1 (Ki-67) antigen to determine the labeling index. In addition, DNA ploidy was assessed after Feulgen staining. Actuarial cancer-related survival, no evidence of disease survival, and colostomy-free survival rates at five years were 81, 76, and 86 percent, respectively. In univariate analysis, T category (T1/2 vs. T3/4) was predictive for no evidence of disease survival (87 vs. 59 percent; P = 0.03) and colostomy-free survival (94 vs. 73 percent; P = 0.05). N category (N0 vs. N1-3) influenced actuarial cancer-related survival (85 vs. 58 percent; P = 0.002) and no evidence of disease survival (80 vs. 53 percent; P = 0.02). A higher proliferative potential as measured by the MIB1 labeling index was associated with a better colostomy-free survival (90 vs. 50 percent; P = 0.04). In multivariate analysis, actuarial cancer-related survival was only influenced by the N category (P = 0.03) and no evidence of disease survival by N category (P = 0.03) and mitomycin C dose (P = 0.04). Salvage abdominoperineal resection achieved long-term control in only four of seven patients with local failures. Treatment with a combination of radiotherapy and chemotherapy is safe and effective for patients with anal canal carcinoma. Abdominoperineal resection is indicated as a salvage procedure in nonresponding and recurrent lesions and may be of benefit in a small subgroup of patients with poor prognostic factors.


Stabilization of transcobalamins against heating on sephadex G-50.
The human serum stabilized on Sephadex G-50 did not show any changes in the distribution of radioactive vitamin B12 bound to transcobalamins during incubation at 56 degrees C (30 and 120 min.) and 80 degrees C (20 min.), whereas, in the non-stabilized serum, heating increased the vitamin 57CoB12 in transcobalamin I and III fraction and decreased or completely abolished the amount of radioactive vitamin B12 bound to transcobalamin II.


Process Analytical Utility of Raman Microspectroscopy in the Directed Differentiation of Human Pancreatic Insulin-Positive Cells.
Continued advances toward cell-based therapies for human disease generate a growing need for unbiased and label-free monitoring of cellular characteristics. We used Raman microspectroscopy to characterize four important stages in the 26-day directed differentiation of human embryonic stem cells (hESCs) to insulin-positive cells. The extent to which the cells retained spectroscopic features of pluripotent cells or developed spectroscopic features suggestive of pancreatic endocrine cells, as well as assessing the homogeneity of the cell populations at these developmental stages, were of particular interest. Such information could have implications for the utility of Raman microspectroscopy process analysis for the generation of insulin-positive cells from hESCs. Because hESC seeding density influences the subsequent pancreatic development, three different seeding density cultures were analyzed. Transcription factor and other marker analyses assessed the progress of the cells through the relevant developmental stages. Increases in the Raman protein-to-nucleic acid band ratios were observed at the final endocrine stage analyzed, but this increase was less than expected. Also, high glycogen band intensities, somewhat unexpected in pancreatic endocrine cells, suggested the presence of a substantial number of glycogen containing cells. We discuss the potential process analytical technology application of these findings and their importance for cell manufacturing.


Perioperative systemic chemotherapy for peritoneal mucinous appendiceal carcinomas treated with cytoreductive surgery & HIPEC.
To identify the role of systemic chemotherapy in the management of appendiceal malignancies. Over a 10-year period (2005 -2014), 52 patients with appendiceal neoplasms were treated at our Peritoneal Surface Malignancy Unit [14 (26.9%) disseminated peritoneal adenomucinosis (DPAM), 30 (57.7%) peritoneal mucinous carcinomatosis of appendiceal origin (PMCA) and 8 (15.4%) PMCA-I]. All patients (100%) underwent cytoreductive surgery (CRS) & hyperthermic intraperitoneal chemotherapy (HIPEC), while 20 (38.5%) of them also received perioperative systemic chemotherapy. Mean peritoneal cancer index (PCI) was 23.6. Completeness of cytoreduction score (CC-S) was: CC-0 in 26 patients (50%), CC-1 in 20 patients (38.5%) and CC-2 in 6 patients (11.5%). High grade malignancy was reported in 27 patients (51.9%) and low grade malignancy in 25 patients (48.1%). More than half of the patients developed recurrence (n=36, 69.2%), while death was reported in 40.4% (n=21). Median overall survival (OS) in all histologic groups was 24 months for patients who received perioperative systemic chemotherapy and 14 months for patients who did not (p=0.048). Median disease free survival (DFS) in all histologic groups was 19 months for patients who received perioperative systemic chemotherapy and 10 months for patients who did not (p=0.034). We suggest that perioperative systemic chemotherapy serves as a helpful therapeutic tool in the management of peritoneal mucinous appendiceal carcinomas treated with cytoreductive surgery & HIPEC.


Current Knowledge and Computational Techniques for Grapevine Meta-Omics Analysis.
Growing grapevine (Vitis vinifera) is a key contribution to the economy of many countries. Tools provided by genomics and bioinformatics did help researchers in obtaining biological knowledge about the different cultivars. Several genetic markers for common diseases were identified. Recently, the impact of microbiome has been proved to be of fundamental importance both in humans and in plants for its ability to confer protection or induce diseases. In this review we report current knowledge about grapevine microbiome, together with a description of the available computational methodologies for meta-omics analysis.


Seizures in tramadol overdoses reported in the ToxIC registry: predisposing factors and the role of naloxone.
Importance: Tramadol prescriptions have increased as fewer schedule II and III drugs are prescribed. There has been a concomitant increase in overdoses and adverse events recorded in the National Poison Data System. Seizure activity after tramadol overdose or therapeutic use is a well-documented adverse event. The primary objective is to evaluate the characteristics associated with seizures following single agent tramadol ingestion. Secondarily we aim to compare the rate of seizures in individuals treated, and not treated, with naloxone. Methods: We searched the Toxicology Investigators Consortium data registry for all cases of single agent tramadol ingestions from 01/01/2014 through 12/31/2017. Descriptive statistics were used to evaluate characteristics associated with increased risk of seizures. Binary logistic regressions were used to evaluate the associations between seizures and age, race, acuity, intent, toxidromes, symptoms, and treatments. Results: There were 80 single ingestion tramadol cases entered into the registry. Seizures developed in 42 (52.5%) patients. Asian patients (OR = 7.2, 95% CI: 1.9-27.3, p = .004) and patients abusing or misusing tramadol (OR = 3.2, 95% CI: 1.2-8.3, p = .02) more likely to develop seizures. Patients exhibiting an opioid toxidrome were significantly less likely to develop seizures (OR = 0.12, 95% CI: 0.03-0.60). Ingestion of tramadol as a means of self-harm and age were not associated with an increased risk of seizures. There was no significant association between naloxone administration and seizures (OR = 0.30, 95% CI 0.07-1.25). Conclusions: Based on data from the ToxIC registry, tramadol induced seizures are more likely in Asian patients and those abusing or misusing the medication. There was no association found between the development of seizures and the use of naloxone.


Applicability of the PRECISE-DAPT score in elderly patients with myocardial infarction.
Elderly patients with acute coronary syndromes (ACS) are at higher risk both for ischemic and bleeding complications. Current guidelines recommend the PRECISE-DAPT score for bleeding risk stratification in this setting, but no study assessed its applicability in elderly patients. This study aimed to assess the performance of the PRECISE-DAPT score in a series of non-selected elderly patients with ACS from routine clinical practice. The IFFANIAM registry included prospectively patients aged ≥ 75 years with ST segment elevation myocardial infarction (STEMI). Main outcome measured was the incidence of relevant bleeding after discharge (bleeding leading to hospital readmission, need for transfusion, intervention, stop of antithrombotic drugs or death). Bleeding risk was classified: (A) according to PRECISE-DAPT values above or not the recommended cut-off point (≥ 25); and (B) according to the quartiles of PRECISE-DAPT values observed in the IFFANIAM series (Q1: < 30; Q2: 30-35; Q3: 36-44; Q4: ≥ 45). A total of 208 patients were included. Mean age was 81.9 ± 4.5 years. Most patients (92.6%) had a PRECISE-DAPT value > 25. A total of 25 patients (12.0%) had bleeding events and 49 patients (23.6%) died. No significant differences regarding the incidence of bleeding were observed according to the recommended cutt of point ≥ 25. However, a progressive increase in the incidence of bleeding was observed across PRECISE-DAPT quartiles observed in this series (P = 0.038). The vast majority of elderly patients have PRECISE-DAPT values above the recommended cut-off point for bleeding risk. Using different cut-off points could be a more rational approach for predicting bleeding risk in these complex patients.


A Rapid Diagnostic Technique to Discriminate between Two Pests of Palms, Brontispa longissima and Octodonta nipae (Coleoptera: Chrysomelidae), for Quarantine Applications.
Octodonta nipae (Maulik) is morphologically and biologically similar to Brontispa longissima (Gestro), one of the most damaging pests of coconut. The two species share several palm hosts and produce similar symptoms. They are easily confused when they invade a new area, and without professional taxonomic expertise accurate identification is arduous and time-consuming. Thus, a method of rapidly distinguishing these two invasive insects rapidly is critical for quarantine. Based on the first internal transcribed spacer and the mitochondrial cytochrome oxidase I gene, two pairs of special primers and corresponding polymerase chain reaction processes have been developed to enhance a single objective band only from the O. nipae DNA template. This will quickly discriminate between these two species. The present results provide a rapid method of distinguishing O. nipae from B. longissima to help avoid misidentification, and furthermore, to facilitate rapid and appropriate quarantine decisions and effective treatments to the pest.


Testicular Dislocation After Unstable Pelvic Ring Injury.
Reproductive and genitourinary complications following pelvic ring injuries have been described; however, testicular dislocation is rare and can cause significant morbidity if not managed appropriately. We describe a case of testicular dislocation after pelvic ring injury and outline the subsequent management and outcome, and seek to identify areas of improvement to ensure expedient and appropriate care in the setting of these injuries. Our case describes a 29-year-old male who presented to a level-one trauma center following a motorcycle collision. An anteroposterior compression type II rotationally unstable pelvic ring was identified on imaging. He was hemodynamically unstable and computed tomography (CT) with angiography was ordered. Arterial extravasation was noted from the bilateral anterior internal iliac arteries, which were subsequently embolized by interventional radiology. However, no concomitant genitourinary injury was identified at the time of CT. After resuscitation, the pelvis was stabilized with an anterior symphyseal plate and bilateral sacroiliac screws. During the anterior pelvic approach, the patient's dislocated testicle was surprisingly discovered inferior to the pubis. Urology was consulted intra-operatively, and the testicle was successfully relocated. At the final follow-up, the pelvic ring was healed without any noticeable urogenital complication. While testicular dislocation has been reported in the setting of pelvic ring injury, a paucity of information exists regarding management, implications, and areas for improvement in the identification of these injuries. Therefore, in cases of pelvic ring injury with significant trauma, radiologists, traumatologists, and orthopedic surgeons should adopt a multi-disciplinary approach in diligently attempting to rule out testicular dislocation pre-operatively. Intra-operatively, examination under anesthesia and careful operative technique are important in preventing iatrogenic injury.


Anaerobic bacteria, the colon and colitis.
Anaerobic bacteria constitute more than 90% of the bacteria in the colon. An anaerobic environment is needed to maintain their growth and the production of short-chain fatty acids by these bacteria from carbohydrates. Short-chain fatty acids are rapidly absorbed and essential for metabolic as well as functional welfare of the colonic mucosa. The importance of these acids in water absorption and in the patogenesis of colitis is discussed in relation to the concept of "energy deficiency diseases" of the colonic mucosa.


Identification of Nepsilon-(carboxymethyl)lysine-positive cells in astroglia-rich primary cultures.
Astroglia-rich primary cultures from rat brain were used to investigate the presence in glial cells of Nepsilon-(carboxymethyl)lysine (CML), an advanced glycation endproduct. Westernblot analysis of homogenates of rat brain as well as of astroglia-rich cultures demonstrated the presence of CML-modified proteins in these samples. Immunocytochemical staining of astroglia-rich cultures revealed that only a minority of the cells in these cultures were intensively stained for CML. The staining intensity of CML-positive cells was strongly reduced, if the cells were not permeabilized, indicating that intracellular proteins were CML-modified. The CML-positive cells were identified as astrocytes and oligodendrocytes by double-labelling immunocytochemical staining for CML and the cellular markers galactocerebroside, myelin basic protein and glial fibrillary acidic protein. In contrast to other glial cells, microglial cells in astroglia-rich cultures were CML-negative. The finding that only a minority of cells in astroglia-rich cultures contains high amounts of intracellular CML-modified proteins indicates that specific properties of these CML-positive cells are responsible for the CML-formation in these cells.


Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis.
Microarray analysis of multiple sclerosis (MS) lesions obtained at autopsy revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin-6 and -17, interferon-gamma and associated downstream pathways. Comparison of two poles of MS pathology--acute lesions with inflammation versus 'silent' lesions without inflammation--revealed differentially transcribed genes. Some products of these genes were chosen as targets for therapy of experimental autoimmune encephalomyelitis (EAE) in mice. Granulocyte colony-stimulating factor is upregulated in acute, but not in chronic, MS lesions, and the effect on ameliorating EAE is more pronounced in the acute phase, in contrast to knocking out the immunoglobulin Fc receptor common gamma chain where the effect is greatest on chronic disease. These results in EAE corroborate the microarray studies on MS lesions. Large-scale analysis of transcripts in MS lesions elucidates new aspects of pathology and opens possibilities for therapy.


Transplantation of neuronal and glial restricted precursors into contused spinal cord improves bladder and motor functions, decreases thermal hypersensitivity, and modifies intraspinal circuitry.
Transplanting neuronal and glial restricted precursors (NRP/GRP) into a midthoracic injury 9 d after contusion improved bladder and motor function, diminished thermal hypersensitivity, and modified lumbosacral circuitry compared with operated controls (OP-controls). Histological analysis showed that NRP/GRP survived, filled the lesion site, differentiated into neurons and glia, and migrated selectively. Volume of spinal cord spared was increased in NRP/GRP recipients, suggesting local protection. Bladder areflexia developed in both operated groups, but NRP/GRP recipients exhibited an accelerated recovery, with decreased micturition pressure and fewer episodes of detrusor hyperreflexia. Because noradrenergic receptors proliferate after spinal injury and descending noradrenergic pathways contribute to regulation of bladder control, we examined the effects of administering an alpha-1A-adrenergic antagonist, Tamsulosin, on urodynamics. This improved all cystometric parameters in both operated groups, and micturition pressure in NRP/GRP rats recovered to normal levels. Both operated groups initially showed increased sensitivity to a thermal stimulus applied to the tail; the NRP/GRP rats showed significant improvement over time. NRP/GRP grafts also produced greater recovery of hindlimb function in several tests, although both groups showed persistent and similar deficits in locomotion on a grid. Because bladder, hindlimb, and tail sensory and motor functions are organized through lumbosacral cord, we examined descending and primary afferent projections at L6-S1. The density of serotonergic, noradrenergic, and corticotrophin releasing factor-positive fibers increased in the NRP/GRP group compared with OP-controls, suggesting some sparing and/or sprouting of these modulatory pathways. Immunocytochemical staining density of dorsal root axons in the dorsal horn increased in the OP-controls but appeared normal in the NRP/GRP group. Synaptophysin immunoreactivity in the lumbosacral dorsal horn was similar among groups, consistent with restoration of synaptic density in both groups of operated animals but by different pathways. We suggest that local protection provided by NRP/GRP resulted in increased sparing/sprouting of descending pathways, which prevented sprouting by dorsal root axons, and that this modification in lumbosacral circuitry contributes to the recovery of function.


Reversible basal plane hydrogenation of graphene.
We report the chemical reaction of single-layer graphene with hydrogen atoms, generated in situ by electron-induced dissociation of hydrogen silsesquioxane (HSQ). Hydrogenation, forming sp3 C--H functionality on the basal plane of graphene, proceeds at a higher rate for single than for double layers, demonstrating the enhanced chemical reactivity of single sheet graphene. The net H atom sticking probability on single layers at 300 K is at least 0.03, which exceeds that of double layers by at least a factor of 15. Chemisorbed hydrogen atoms, which give rise to a prominent Raman D band, can be detached by thermal annealing at 100-200 degrees C. The resulting dehydrogenated graphene is "activated" when photothermally heated it reversibly binds ambient oxygen, leading to hole doping of the graphene. This functionalization of graphene can be exploited to manipulate electronic and charge transport properties of graphene devices.


Kinetics and mechanism of the manganese(II) catalysed Calmagite dye oxidation using in situ generated hydrogen peroxide.
The kinetics and mechanism for the bleaching of Calmagite (H3CAL, 3-hydroxy-4-(2-hydroxy-5-methylphenylazo)naphthalene-1-sulfonic acid) in aqueous solution at pH 8.00 and 23 ± 1 °C using in situ generated H2O2 is described. Complete mineralisation of H3CAL results with turnover frequencies (TOF = moles of H3CAL bleached per mole of manganese per hour) of 40 h(-1). The monohydroxy azo dyes Me-H2CAL, Orange G and Orange II are not bleached which indicates that a requirement of dye bleaching is the coordination of the dye to the Mn centre. Spectroscopic studies show the formation of Mn(CAL)2 and Mn(CAL) species but in the presence of Tiron (1,2-dihydroxybenzene-3,5-disulfonate, disodium salt, monohydrate, Na2TH2·H2O), [Mn(CAL)(T)] is formed. It is proposed that a Mn(III)-hydroperoxide species is generated, [Mn(O2H)(CAL)(TQ)] from the in situ generated H2O2, where TQ represents the o-quinone form of Tiron, and this is the active species in the bleaching of coordinated CAL; the formation of this hydroperoxide species is supported by UV/VIS and ESI-MS data. The formation of a Mn(III) species is supported by EPR studies which also show some evidence for the presence of a labile d(5) Mn(II) species in the presence of the reducing substrate hydroxylamine (NH2OH). This would enable rapid ligand exchange for both in situ H2O2 generation and dye bleaching to occur; there is no evidence for the presence of Mn(IV)=O species. The virtue of low local concentrations of in situ generated H2O2 is shown to be important in preventing over oxidation of the catalyst and thus contributing to a robust catalytic system.


Time-Domain and Spectral-Domain Optical Coherence Tomography of Retinal Nerve Fiber Layer in MS Patients and Healthy Controls.
Objective. The aim of this study was to compare retinal nerve fiber layer thickness (RNFLT) between spectral-domain (SD-) and time-domain optical coherence tomography (TD-OCT) in MS patients and healthy controls (HC). Furthermore, RNFLT between MS eyes with and without optic neuritis (ON) and HC should be explored. Finally, the relationship between RNFLT, disease duration, EDSS, and disease modifying therapy (DMT) should be established. Design. Prospective, cross-sectional study. Participants. 28 MS patients and 35 HC. Methods. Both groups underwent TD- and SD-OCT measurements. RFNLT was correlated between the two machines and between MS eyes with and without ON and HC. Furthermore, RNFLT was correlated to disease duration, EDSS and DMT. Results. A strong correlation (Pearson's r = 0.921, P < 0.001), but a statistically significant difference of 2 μm (P < 0.001), was found between the two devices. RNFLT was significantly different between MS eyes with history of ON (mean RFNLT (SD) 72.21 μm (15.83 μm)), MS eyes without history of ON 93.03 μm (14.25 μm), and HC 99.07 μm (7.23 μm) (P < 0.001). Conclusions. The measurements between different generation of OCT machines are not interchangeable, which should be taken into account if comparing results between different machines and switching OCT machine in longitudinal studies.


Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution.
Increased brain size, relative to body mass, is a primary characteristic distinguishing the mammalian lineage. This greater encephalization has come with increased behavioral complexity and, accordingly, it has been suggested that selection on behavioral traits has been a significant factor leading to the evolution of larger whole-brain mass. In addition, brains may evolve in a mosaic fashion, with functional components having some freedom to evolve independently from other components, irrespective of, or in addition to, changes in size of the whole brain. We tested whether long-term selective breeding for high voluntary wheel running in laboratory house mice results in changes in brain size, and whether those changes have occurred in a concerted or mosaic fashion. We measured wet and dry brain mass via dissections and brain volume with ex vivo magnetic resonance imaging of brains that distinguished the caudate-putamen, hippocampus, midbrain, cerebellum and forebrain. Adjusting for body mass as a covariate, mice from the four replicate high-runner (HR) lines had statistically larger non-cerebellar wet and dry brain masses than those from four non-selected control lines, with no differences in cerebellum wet or dry mass or volume. Moreover, the midbrain volume in HR mice was ~13% larger (P<0.05), while volumes of the caudate-putamen, hippocampus, cerebellum and forebrain did not differ statistically between HR and control lines. We hypothesize that the enlarged midbrain of HR mice is related to altered neurophysiological function in their dopaminergic system. To our knowledge, this is the first example in which selection for a particular mammalian behavior has been shown to result in a change in size of a specific brain region.


Needles to promote ventricular blood into the ischemic myocardium applied in a rat heart transplant model: an acute observation [corrected].
Two needles were designed in order to revascularize an ischemic myocardium in the event of left coronary artery occlusion. This study was conducted by performing the Lee modified Fox-Montorsi heart-lung transplant on 25 San Diego Microsurgical Institute-bred Sprague Dawley rats that were subjected to left coronary artery ligation in each case. Of these 25 rats, a straight-porous (SP) needling procedure was applied to 9 heterotopically transplanted rat hearts, and a distinct horseshoe (HS)-shaped needle application was performed on the remaining 16 heterotopically transplanted rat hearts. This report represents an acute study on the efficiency of these two needles to transmit oxygen-rich blood from the left ventricle into the ischemic myocardium. Doppler readings for male vs. female transplants showed that the control peak (PK) and mean (MN) kHz values are on the average of 0.20 kHz higher in males than in females. However, control heart rate values in both sexes are approximately equal. Ligation of the left coronary artery caused a dramatic decrease of PK and MN kHz values in both sexes, while heart rate showed no significant decrease from the original control values in response to ischemia. Application of the SP needle showed only a slight return of PK and MN values in both sexes, but heart rate values increased to levels higher than the original control values. The HS needling procedure was able to recover approximately 80% of the control PK and MN kHz values in both sexes. Thus, these data indicate that the HS needle can successfully transmit left ventricular blood into the myocardium.


[Seasonal Variation and Sources Identification of Dissolved Sulfate in a Typical Karst Subterranean Stream Basin Using Sulfur and Oxygen Isotopes].
Karst water, which provides approximately 25% of the world's drinking water, is especially vulnerable to anthropogenic pollutants. To determine the variations between high and low flow periods and the sources of dissolved sulfate (SO42-) in small karst basins, SO42- concentrations, stable sulfur and oxygen isotopes (δ34S-SO4 and δ18O-SO4), and oxygen isotopes of water (δ18O-H2O) were investigated in surface and groundwaters, during the high and low flow seasons, within the Babu subterranean stream basin. Analysis showed that: ① the water samples that were directly impacted by acid mine drainage exhibited high SO42- concentrations (≥250 mg·L-1) and significant seasonal variation, while the seasonal variation of non-AMD-impacted water with low SO42- concentrations was not significant. ② During the high flow season, the mean δ34S-SO4 and δ18O-SO4 values of surface water were -10.5‰ and 4.7‰, respectively, and -11.5‰ and 1.3‰ during the low flow period; the mean values of δ34S-SO4 and δ18O-SO4 in groundwater samples were -2.9‰ and 7.1‰ during the high flow period, respectively, and -3.2‰ and 6.2‰ during the low flow period. Both surface and groundwater samples exhibited higher δ34S-SO4 and δ18O-SO4 values during the high flow period than during the low flow period. ③ The values of δ34S-SO4 in the surface and groundwater samples were relatively stable, indicating that the sources of SO42- at specific sampling sites were stable.④ The main sources of SO42- in surface and groundwaters were rain, sulfide, and gypsum, accounting for 13%, 40%, and 47%, respectively, of SO42- in samples taken from the basin outlet during the high flow season, and 18%, 39%, and 43%, respectively, in samples obtained during the low flow season.


Combinatorial microRNA target predictions.
MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3' untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript. Different combinations of microRNAs are expressed in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published microRNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results suggest widespread coordinate control executed by microRNAs. In particular, we experimentally validate common regulation of Mtpn by miR-375, miR-124 and let-7b and thus provide evidence for coordinate microRNA control in mammals.


Direct test of the "quantum vampire's" shadow absence with use of thermal light.
The counterintuitive nature of quantum physics leads to a number of paradoxes. One of them is a "quantum vampire" effect [Fedorov et al., Optica2, 112 (2015)OPTIC82334-253610.1364/OPTICA.2.000112], which means that the photon annihilation in a part of a large beam does not change the shape of the beam profile (i.e., does not cast a shadow), but it may change the total beam intensity. Previously, this effect was demonstrated just in a simplified double-mode regime [Fedorov et al., Optica2, 112 (2015), OPTIC82334-253610.1364/OPTICA.2.000112 Katamadze et al., Optica5, 723 (2018)OPTIC82334-253610.1364/OPTICA.5.000723]. In this Letter, a direct test of shadow absence after the photon annihilation was performed using the thermal state of light at the input.


Efficacy of Dressing with Absorbent Foam versus Dressing with Gauze in Prevention of Tracheostomy Site Infection.
Tracheostomy site infection can cause numerous problems. Absorbent foam dressing may be able to prevent proliferation of infectious microorganisms by absorbing the tracheostomy stoma exudate. This study aimed to compare the efficacy of absorbent foam with gauze dressing for prevention of tracheostomy site infection. In this double-blind randomized clinical trial, 80 patients (18 to 60 years) hospitalized in the intensive care unit (ICU) due to severe head injury were randomly divided into two groups and early tracheostomy was done for them during the first 2 days. In the first group, gauze was used as tracheostomy site dressing, while in the second, absorbent foam, was placed. Tracheostomy site was checked daily for any sign of infection and samples were taken from the stoma for culture in case of presence of any sign of infection. Of a total of 80, 11 had tracheostomy site infection (13.75%), including 7 (17.5%) in the gauze group and 4 (10%) in the foam group. The difference in this regard between the two groups was not significant (P=0.051). Also, the dominant strains in the culture of gauze group were hospital-acquired Gram-negative bacteria (particularly Acinetobacter), while in the foam group, Gram-positives and more commonly Staphylococcus epidermidis were found. Absorbent foam dressing is not superior to gauze dressings for prevention of tracheostomy site infection.


CT-guided liver biopsy with electromagnetic tracking: results from a single-center prospective randomized controlled trial.
The purpose of this study is to evaluate the effectiveness of electromagnetic tracking in assisting CT-guided liver biopsies. This was a single-center prospective randomized controlled trial comparing nonfluoroscopic CT-guided liver biopsy using an advance-and-scan technique with and without electromagnetic tracking. Fifty patients with a liver lesion referred for biopsy (women, 52%; mean age, 59.7 years; mean lesion size, 3.6 cm) were enrolled in the study and were randomly assigned to either arm. The primary and secondary objectives were to assess and quantify differences in the number of intraprocedural scans, cumulative effective radiation dose, number of needle manipulations, and procedure time from skin-stick to the target lesion with and without assistance. Electromagnetic tracking significantly decreased the number of scans, effective radiation dose, number of manipulations per procedure, and time from skin-stick to the target lesion. The ratio of the number of scans (electromagnetic tracking to control) was 0.55 (95% CI, 0.42-0.73; p<0.0001). The mean difference in effective radiation dose (electromagnetic tracking-control) was -4.7 mSv (95% CI, -7.01 to -2.44 mSv; p=0.0001), and the median difference was -5.1 mSv (95% CI, -7.01 to -3.56 mSv; p<0.0001). The ratio of the number of manipulations (electromagnetic tracking to control) was 0.36 (95% CI, 0.24-0.54; p<0.0001). The mean difference for the time from skin-stick to the target lesion was -247.6 seconds (95% CI, -394.34 to -100.83 seconds; p=0.0014) and the median difference was -253.0 seconds (95% CI, -325.00 to -124.00 seconds; p=0.0001). Electromagnetic tracking assistance has the potential to decrease the number of intraprocedural CT scans and needle manipulations and to reduce patient radiation dose during CT-guided liver biopsy.


Adult children's socioeconomic resources and mothers' survival after a breast cancer diagnosis: a Swedish population-based cohort study.
Socioeconomic inequalities in survival after breast cancer persist worldwide. We aim to determine whether adult offspring's socioeconomic resources contribute to inequalities in mothers' survival after breast cancer. 14 231 women, aged 65-79 years, with a child aged ≥30 years and a first primary diagnosis of breast cancer in the National Cancer Register between 2001 and 2010 were followed until death, 10 years after diagnosis, or end of study (December 2015). Relative survival proportions and excess mortality within 10 years of diagnosis by strata of offspring's education level and disposable income were estimated using flexible parametric models accounting for measures of mothers' socioeconomic position and expected mortality in the general population. 4292 women died during 102 236 person-years of follow-up. Crude 10-year relative survival proportions for mothers of children with >14, 12-14 and <12 years of education were 0.89 (0.87 to 0.91), 0.87 (0.85 to 0.89) and 0.79 (0.76 to 0.81), respectively. Compared with mothers of children with >14 years of education, mothers of children with <12 or 12-14 years of education had substantially higher excess mortality (excess HR 1.69 (1.38 to 2.07) and 1.22 (1.00 to 1.48), respectively). Higher mortality did not differ between tertiles of offspring's disposable income. Adult offspring's education level may contribute to inequalities in mothers' survival after breast cancer. Clinicians should be aware of the educational context beyond the individual and women with less educated offsprings may require extra support. This should be considered in future research, policy frameworks and interventions aimed at reducing survival inequalities.


Influence of different culture solutions on osteoblastic differentiation in cord blood and bone marrow derived progenitor cells.
Mesenchymal progenitor cells derived from cord blood (unrestringated somatic stem cells, USSC) and bone marrow (mesenchymal stem cells, MSC) are able to differentiate under defined culture conditions into at least bone, cartilage, adipose and muscle cells in vitro. The culture media and other in vitro conditions influence the osteogenic differentiation potency of both cell types. To increase and expand the number of osteoblasts in vitro an optimization of culture conditions is required. The aim of this study was to evaluate different culture media toward their osteogenic promoting capacity on human USSCs and MSCs in vitro. Immunohistochemical stainings against osteonectin (ON), osteopontin (OP) served as markers for an osteoblastic differentiation. Cellular morphology was analysed by light microscopy technique. We found significant differences between bone marrow and cord blood derived stem cells towards an osteoblastic differentiation. Considering the number of osteoblasts MesenCult seems to have advantages in bone marrow progenitor cells, whereas low glucose DMEM and HAMS-F12 promoted an osteoblastic differentiation in cord blood derived cells more than other tested media.


Tissue expansion for the treatment of myelomeningocele. Case report.
A baby boy who had been born with a large myelomeningocele had a ventriculoperitoneal shunt inserted at the age of 6 months. Two months later it was revised, after which he developed satisfactorily both mentally and physically. He presented at the age of 13 months because the epithelialisation of the myelomeningocele was both fragile and incomplete. Enough soft tissue was obtained to cover the defect, which was 13 x 10 cm, by the use of two 600 ml expanders placed subcutaneously one on either side of the deformity.


Zoledronic acid-associated symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): report of baboon syndrome in a woman with recurrent metastatic breast cancer after receiving zoledronic acid.
Baboon syndrome is a distinctive skin reaction in which the patient typically develops erythematous buttocks that appear similar to those of a baboon. The non-contact allergenic variant of baboon syndrome is also referred to as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). Zoledronic acid is a bisphosphonate that is used in patients with metastatic cancer to prevent bone complications. Zoledronic acid-associated baboon syndrome is described in a woman with recurrent metastatic breast cancer. PubMed was used to search the following terms, separately and in combination: baboon syndrome, breast cancer, symmetrical drug-related intertriginous and flexural exanthema, and zoledronic acid. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated. Zoledronic acid has infrequently been associated with mucocutaneous adverse reactions. However, baboon syndrome has not previously been observed in patients receiving zoledronic acid. The reported woman developed baboon syndrome after her initial exposure to zoledronic acid. Non-contact allergenic drug-induced baboon syndrome has most commonly been associated with antibiotics such as beta-lactams and penicillins. Zoledronic acid-associated baboon syndrome has not previously been observed in cancer patients. Baboon syndrome (SDRIFE variant) was observed in a woman with recurrent metastatic breast cancer after her first exposure to zoledronic acid. In summary, SDRIFE can occur in oncology patients receiving zoledronic acid and zoledronic acid should be added to the list of medications associated with the potential to cause non-contact allergenic drug-induced baboon syndrome.


Impacts of spruce budworm defoliation on the habitat of woodland caribou, moose, and their main predators.
Forest logging has contributed to the decline of several woodland caribou populations by causing the fragmentation of mature coniferous stands. Such habitat alterations could be worsened by spruce budworm (SBW) outbreaks. Using 6201 vegetation plots from provincial inventories conducted after the last SBW outbreak (1968-1992) in boreal forests of Québec (Canada), we investigated the influence of SBW-caused tree defoliation and mortality on understory vegetation layers relevant to woodland caribou and its main predators. We found a positive association between severe outbreaks and the cover of most groups of understory plant species, especially in stands that were dominated by balsam fir before the outbreak, where a high canopy openness particularly benefited relatively fast-growing deciduous plants. Such increases in early successional vegetation could provide high-quality forage for moose, which is likely to promote higher wolf densities and increase predation pressure on caribou. SBW outbreaks may thus negatively affect woodland caribou by increasing predation risk, the main factor limiting caribou populations in managed forests. For the near future, we recommend updating the criteria used to define critical caribou habitat to consider the potential impacts of spruce budworm defoliation.


Severe open tibial fractures: a study protocol.
A prospective randomized study of severe open tibial fractures (Type II and III) was performed. Individual fractures were randomized to treatment groups according to initial antibiotic therapy: One consisted of a first-generation cephalosporin, and the other consisted of a third-generation cephalosporin. Initial antibiotic therapy was given in all patients for 48 h and then specific antibiotic treatment was used as indicated by culture. The purpose of this study was to determine whether or not additional gram-negative coverage had an effect on the overall infection rate or the type of infection in severe open tibial fractures. Additional factors, such as the timing of bone grafts and soft tissue coverage, were evaluated in this study as well. Although there was no statistical difference in the rate of infection with the use of a first- versus a third-generation cephalosporin, there was a trend toward a decreased infection rate as well as toward less morbid infections with the use of a third-generation cephalosporin. The study also confirms that early bone graft should not be performed prior to 6 weeks post injury or after successful soft tissue coverage has been achieved. On the other hand, soft tissue coverage procedures should be performed at the earliest possible date to decrease the overall infection rate.


Therapeutic angiogenesis of adipose-derived stem cells for ischemic diseases.
Ischemic diseases, the leading cause of disability and death, are caused by the stenosis or obstruction of arterioles/capillaries that is not compensated for by vessel dilatation or collateral circulation. Angiogenesis is a complex process leading to new blood vessel formation and is triggered by ischemic conditions. Adequate angiogenesis, as a compensatory mechanism in response to ischemia, may increase oxygen and nutrient supplies to tissues and protect their function. Therapeutic angiogenesis has been the most promising therapy for treating ischemic diseases. In recent years, stem cell transplantation has been recognized as a new technique with therapeutic angiogenic effects on ischemic diseases. Adipose-derived stem cells, characterized by their ease of acquisition, high yields, proliferative growth, and low immunogenicity, are an ideal cell source. In this review, the characterization of adipose-derived stem cells and the role of angiogenesis in ischemic attack are summarized. The angiogenic effects of adipose-derived stem cells are discussed from the perspectives of in-vitro, in-vivo, and clinical trial studies for the treatment of ischemic diseases, including ischemic cardiac, cerebral, and peripheral vascular diseases and wound healing. The microvesicles/exosomes released from adipose-derived stem cells are also presented as a novel therapeutic prospect for treating ischemic diseases.


Steam reforming of tar model compound using Pd catalyst on alumina tube.
Gasification processing of biomass as a renewable energy source generates tar in the product gas. Tar leads to foul-up of the process equipment by corrosion and deposit formation. Catalytic elimination of tars is a crucial step to improve fuel gas quality from the process. In this study, a palladium catalyst on alumina (Pd/Al2O3) was used in steam reforming of benzene as a biomass gasification tar model compound. The reaction was carried out in a laboratory-scale tube reactor made of stainless steel to study the effect of reaction temperature, catalyst loading, quantity of palladium catalyst tubes, steam to carbon ratio (S/C), and residence time on catalytic performance and stability. Pd/Al2O3 showed high efficiency ofbenzene decomposition and enhanced the formation of fuel gas. Hydrogen and carbon conversions increased with reaction temperature. Although the benzene concentration increased from 2000 to 5000 mg/l, the catalytic performance at 600 degrees C and 800 degrees C was similar. 1.0 wt% Pd/Al2O3 showed excellent catalytic activity with the highest hydrogen and carbon conversions of 83% and 81%, respectively at 800 degrees C. This result is attributed to the smooth surface of the palladium, as noted from scanning electron microscopy imaging. An S/C of 2 provided the highest conversion. The addition of catalyst from four and seven tubes did not result in any great difference in terms of benzene cracking efficiency. The fourth cyclic usage of 1.0 wt% Pd/Al2O3 exhibited a higher conversion than that of 0.5 wt%.


Predicted structures of cAMP binding domains of type I and II regulatory subunits of cAMP-dependent protein kinase.
The mammalian cAMP-dependent protein kinases have regulatory (R) subunits that show substantial homology in amino acid sequence with the catabolite gene activator protein (CAP), a cAMP-dependent gene regulatory protein from Escherichia coli. Each R subunit has two in-tandem cAMP binding domains, and the structure of each of these domains has been modeled by analogy with the crystal structure of CAP. Both the type I and II regulatory subunits have been considered, so that four cAMP binding domains have been modeled. The binding of cAMP in general is analogous in all the structures and has been correlated with previous results based on photolabeling and binding of cAMP analogues. The model predicts that the first cAMP binding domain correlates with the previously defined fast dissociation site, which preferentially binds N6-substituted analogues of cAMP. The second domain corresponds to the slow dissociation site, which has a preference for C8-substituted analogues. The model also is consistent with cAMP binding in the syn conformation in both sites. Finally, this model has targeted specific regions that are likely to be involved in interdomain contacts. This includes contacts between the two cAMP binding domains as well as contacts with the amino-terminal region of the R subunit and with the catalytic subunit.


Classification of intervertebral disk degeneration with axial T2 mapping.
The aim of this study was to establish an MRI classification system for intervertebral disks using axial T2 mapping, with a special focus on evaluating early degenerative intervertebral disks. Twenty-nine healthy volunteers (19 men, 10 women; age range, 20-44 years; mean age, 31.8 years) were studied, and axial T2 mapping was performed for the L3-L4, L4-L5, and L5-S1 intervertebral disks. Grading was performed using three classification systems for degenerative disks: our system using axial T2 mapping and two other conventional classification systems that focused on the signal intensity of the nucleus pulposus or the structural morphology in sagittal T2-weighted MR images. We analyzed the relationship between T2, which is known to correlate with change in composition of intervertebral disks, and degenerative grade determined using the three classification systems. With axial T2 mapping, differences in T2 between grades I and II were smaller and those between grades II and III, and between grades III and IV, were larger than those with the other grading systems. The ratio of intervertebral disks classified as grade I was higher with the conventional classification systems than that with axial T2 mapping. In contrast, the ratio of intervertebral disks classified as grade II or III was higher with axial T2 mapping than that with the conventional classification systems. Axial T2 mapping provides a more T2-based classification. The new system may be able to detect early degenerative changes before the conventional classification systems can.


Italian experience of pediatric liver transplantation.
The SIGENP Group has created an Italian Liver Transplantation database. The study considers all patients under 18 yr of age on the waiting list or transplanted between 1984 and 2005. Demographic and clinical data were collected and a descriptive analysis was conducted. Kaplan-Meier survival curves were calculated and Cox's proportional-hazards regression analysis were performed to identify predictors of death after transplantation. Twenty-two Italian centers took part and data were collected on 622 cases: only 53.8% of the transplants performed up until 1998 were carried out in Italy, while this was true of 97.7% of the operations performed between 1999 and 2005. Recipient survival curve analysis revealed one-, two- and five-yr survival rates of 88, 87 and 84%, respectively, and a significant improvement in survival after 1998 (p = 0.0322). Cox's analysis identified the following risk factors for death after liver transplantation, i.e. transplantation before 1998, neoplasms or fulminant hepatic failure as indications, being in intensive care at the time of transplantation and retransplantation. The center where the transplant is performed also revealed an influence on patient survival. Thanks to a better patient follow-up and more cooperation between specialists, the mean survival after liver transplantation is improving and Italian children can be transplanted in Italy.


MiR-17-5p and MKL-1 modulate stem cell characteristics of gastric cancer cells.
Effectively targeting cancer stem cells to treat cancer has great therapeutic prospects. However, the effect of microRNA miR-17/MKL-1 on gastric cancer stem cells has not been studied yet. This study preliminarily explored the mechanism of miR-17/MKL-1 in gastric cancer stem cells. Many previous reports have indicated that microRNA and EMT regulated cancer stem cell characteristics, and miR-17 and MKL-1 were involved as a critical gene in migration and invasion in the EMT pathway. Through RT-PCR, Western Blot, flow cytometry, immunofluorescence, sphere formation xenograft tumor assays and drug resistance, the role of miR-17-5p and MKL-1 on promoting stem cell-like properties of gastric cancer were verified in vivo and vitro. Next, MKL-1 targets CD44, EpCAM, and miR -17-5p promoter verified by luciferase assay and ChIP. Besides, the TCGA database analysis found that both miR-17-5p and MKL-1 increased in gastric cancer, and the prognostic survival of the MKL-1 high expression group was reduced. It is found that MKL-1 promotes expression by targeting miR-17, CD44 and EpCAM promoters. Besides, the TCGA database analysis found that both miR-17-5p and MKL-1 increased in gastric cancer, and the prognostic survival of the MKL-1 high expression group was reduced. These findings reveal new regulatory signaling pathways for gastric cancer stem cells, thus it give new insights on potential early diagnosis and/or molecular therapy for gastric cancer.


Endometrial expression and secretion of interleukin-6 throughout the menstrual cycle.
Previous findings revealing reduced endometrial interleukin-6 (IL-6) mRNA expression in patients with recurrent early abortions gave rise to the analysis of IL-6 synthesis in the human endometrium, and how it relates to concentrations in uterine secretions. Endometrial tissues and uterine secretions were collected from patients undergoing hysterectomy. Expression of IL-6 receptor and gp130 mRNA (n = 28) in total endometrium, of IL-6 mRNA in endometrial epithelial and stromal cells, and CD45-positive leukocytes were investigated by RNAase protection assay throughout the cycle. IL-6 protein was assessed in endometrial tissue by immunohistochemistry (n = 32) and in uterine secretions by enzyme-linked immunosorbent assay (ELISA) (n = 33). IL-6 mRNA was expressed at low levels in the proliferative phase, and expression increased progressively in the secretory phase. The increase was attributed to epithelial and stromal cells and leukocytes. Concentrations of IL-6 protein in endometrial glands and in uterine secretions were low in the proliferative phase, and increased 5-10-fold in the mid- to late secretory phase. mRNA expression of IL-6 receptor and gp130 remained constant in total endometrium throughout the menstrual cycle. High concentrations of IL-6 in the mid-secretory phase, the putative implantation window, and a further increase in the late secretory phase, the premenstrual period, support a role of IL-6 in the regulation of endometrial functions.


TLR9 activation induces normal neutrophil responses in a child with IRAK-4 deficiency: involvement of the direct PI3K pathway.
Polymorphonuclear neutrophils (PMN) play a key role in innate immunity. Their activation and survival are tightly regulated by microbial products via pattern recognition receptors such as TLRs, which mediate recruitment of the IL-1R-associated kinase (IRAK) complex. We describe a new inherited IRAK-4 deficiency in a child with recurrent pyogenic bacterial infections. Analysis of the IRAK4 gene showed compound heterozygosity with two mutations: a missense mutation in the death domain of the protein (pArg12Cys) associated in cis-with a predicted benign variant (pArg391His); and a splice site mutation in intron 7 that led to the skipping of exon 7. A nontruncated IRAK-4 protein was detected by Western blotting. The patient's functional deficiency of IRAK-4 protein was confirmed by the absence of IRAK-1 phosphorylation after stimulation with all TLR agonists tested. The patient's PMNs showed strongly impaired responses (L-selectin and CD11b expression, oxidative burst, cytokine production, cell survival) to TLR agonists which engage TLR1/2, TLR2/6, TLR4, and TLR7/8; in contrast, the patient's PMN responses to CpG-DNA (TLR9) were normal, except for cytokine production. The surprisingly normal effect of CpG-DNA on PMN functions and apoptosis disappeared after pretreatment with PI3K inhibitors. Together, these results suggest the existence of an IRAK-4-independent TLR9-induced transduction pathway leading to PI3K activation. This alternative pathway may play a key role in PMN control of infections by microorganisms other than pyogenic bacteria in inherited IRAK-4 deficiency.


[Philosophical aspects. Why the embryo is a issue].
How raising the embryo's issue today ? Far from evidences and certainties, we have to face the confrontations to understand them. Embryo's issue crystalise all cultural and human tensions. Beyond ontological disagrement on the embryo being what can we expect for mankind today and tomorrow ? Through an anthropological thinking, embryo's issue challenges us in our common capability of decision.


Change in muscle strength and muscle mass in older hospitalized patients: A systematic review and meta-analysis.
Hospitalization may induce a decrease of muscle strength and muscle mass in older patients due to physical inactivity, malnutrition and diseases, negatively affecting health outcome. We aimed to examine the literature on change in muscle strength and muscle mass in older patients during hospitalization. A literature search was performed in major electronic databases from inception to March 2016. Studies including hospitalized patients with a mean age≥65years, describing change of hand grip strength and/or muscle mass were found eligible. Extracted data were divided in hand grip strength or muscle mass and stratified by elective or acute admission. Meta-analysis was conducted using Comprehensive Meta-analysis. Twenty-five studies were included, describing a total of 1789 patients with a mean age range of 65 to 85.8years and an overall median length of stay of 14.7days. Pooled hand grip strength and muscle mass were found to significantly decrease in electively admitted older patients during hospitalization (standardized mean difference (95% confidence interval): -0.42 (-0.66, -0.17) and -0.44 (-0.61, -0.27)), but not in acutely admitted older patients (standardized mean difference (95% confidence interval): 0.18 (-0.02, 0.37) and -0.25 (-0.58, 0.09)). In conclusion, decrease in muscle strength and muscle mass in older patients is dependent on the type of admission.


[Analysis of complexity in Chinese meteria medica industrial chain].
Chinese meteria medica (CMM) chain is a long-span chain covering agriculture which mainly depends on the forces of nature as well as high-tech CMM industry, CMM expertise industry and fast developing CMM circulation industry. Imbalance among the development of these industries produces bottlenecks and hinders the operation of the entire production chain. After analyzing the structure of Chinese meteria medica industrial chain from the perspective of national economy industry, three industry classifications and differentiation of factor intensity, we conclude that the complex structure of CMM industry chain is attributable to these three aspects. And the complexity is mainly shown at complex industry, varied product types, different coordination of various industrial sections and different technical growth speed of varied industry. We propose that structural complexity is the natural property of the chain, which is the main reason of industry sector development imbalance and bottleneck. Results of this research could provide theoretical analysis for future research on the coordination of industrial chain and the efficiency of resource allocation.


Kinetics of Leptospira interrogans infection in hamsters after intradermal and subcutaneous challenge.
Leptospirosis is a zoonosis caused by highly motile, helically shaped bacteria that penetrate the skin and mucous membranes through lesions or abrasions, and rapidly disseminate throughout the body. Although the intraperitoneal route of infection is widely used to experimentally inoculate hamsters, this challenge route does not represent a natural route of infection. Here we describe the kinetics of disease and infection in hamster model of leptospirosis after subcutaneous and intradermal inoculation of Leptospira interrogans serovar Copenhageni, strain Fiocruz L1-130. Histopathologic changes in and around the kidney, including glomerular and tubular damage and interstitial inflammatory changes, began on day 5, and preceded deterioration in renal function as measured by serum creatinine. Weight loss, hemoconcentration, increased absolute neutrophil counts (ANC) in the blood and hepatic dysfunction were first noted on day 6. Vascular endothelial growth factor, a serum marker of sepsis severity, became elevated during the later stages of infection. The burden of infection, as measured by quantitative PCR, was highest in the kidney and peaked on day 5 after intradermal challenge and on day 6 after subcutaneous challenge. Compared to subcutaneous challenge, intradermal challenge resulted in a lower burden of infection in both the kidney and liver on day 6, lower ANC and less weight loss on day 7. The intradermal and subcutaneous challenge routes result in significant differences in the kinetics of dissemination and disease after challenge with L. interrogans serovar Copenhageni strain Fiocruz L1-130 at an experimental dose of 2×106 leptospires. These results provide new information regarding infection kinetics in the hamster model of leptospirosis.


Inhibition of Kinesin-5, a microtubule-based motor protein, as a strategy for enhancing regeneration of adult axons.
Developing neurons express a motor protein called kinesin-5 (also called kif11 or Eg5) which acts as a 'brake' on the advance of the microtubule array during axonal growth. Pharmacological inhibition of kinesin-5 causes the developing axon to grow at a faster rate, retract less and grow past cues that would otherwise cause it to turn. Here we demonstrate that kinesin-5 is also expressed in adult neurons, albeit at lower levels than during development. We hypothesized that inhibiting kinesin-5 might enable adult axons to regenerate better and to overcome repulsive molecules associated with injury. Using adult mouse dorsal root ganglion neurons, we found that anti-kinesin-5 drugs cause axons to grow faster and to cross with higher frequency onto inhibitory chondroitin sulfate proteoglycans. These effects may be due in part to changes in the efficiency of microtubule transport along the axonal shaft as well as enhanced microtubule entry into the distal tip of the axon. Effects observed with the drugs are further enhanced in some cases when they are used in combination with other treatments known to enhance axonal regeneration. Collectively, these results indicate that anti-kinesin-5 drugs may be a useful addition to the arsenal of tools used to treat nerve injury.


Synthesis of Glycosyl Amides Using Selenocarboxylates as Traceless Reagents for Amide Bond Formation.
Carbohydrate-derived amides were successfully prepared in good yields from a broad range of substrates, including furanosyl and pyranosyl derivatives. The methodology successfully relied on the in situ generation of lithium selenocarboxylates from Se/LiEt3BH and acyl chlorides or carboxylic acids and their reaction with sugar azides. A key aspect of the present protocol is that we start from elemental selenium; isolation and handling of all reactive and sensitive selenium-containing intermediates is avoided, therefore providing the selenocarboxylate the status of a traceless reagent.


Implementation of mechanism of action biology-driven early drug development for children with cancer.
An urgent need remains for new paediatric oncology drugs to cure children who die from cancer and to reduce drug-related sequelae in survivors. In 2007, the European Paediatric Regulation came into law requiring industry to create paediatric drug (all types of medicinal products) development programmes alongside those for adults. Unfortunately, paediatric drug development is still largely centred on adult conditions and not a mechanism of action (MoA)-based model, even though this would be more logical for childhood tumours as these have much fewer non-synonymous coding mutations than adult malignancies. Recent large-scale sequencing by International Genome Consortium and Paediatric Cancer Genome Project has further shown that the genetic and epigenetic repertoire of driver mutations in specific childhood malignancies differs from more common adult-type malignancies. To bring about much needed change, a Paediatric Platform, ACCELERATE, was proposed in 2013 by the Cancer Drug Development Forum, Innovative Therapies for Children with Cancer, the European Network for Cancer Research in Children and Adolescents and the European Society for Paediatric Oncology. The Platform, comprising multiple stakeholders in paediatric oncology, has three working groups, one with responsibility for promoting and developing high-quality MoA-informed paediatric drug development programmes, including specific measures for adolescents. Key is the establishment of a freely accessible aggregated database of paediatric biological tumour drug targets to be aligned with an aggregated pipeline of drugs. This will enable prioritisation and conduct of early phase clinical paediatric trials to evaluate these drugs against promising therapeutic targets and to generate clinical paediatric efficacy and safety data in an accelerated time frame. Through this work, the Platform seeks to ensure that potentially effective drugs, where the MoA is known and thought to be relevant to paediatric malignancies, are evaluated in early phase clinical trials, and that this approach to generate pre-clinical and clinical data is systematically pursued by academia, sponsors, industry, and regulatory bodies to bring new paediatric oncology drugs to front-line therapy more rapidly.


Effect of Gender on Postoperative Morbidity and Mortality Outcomes: A Retrospective Cohort Study.
Full extent of gender differences on postoperative outcomes has never been studied on large scale, specifically postoperative complications. This study aims to assess the effect of gender on 30-day morbidity and mortality after major surgery. A retrospective cohort study was carried out using data of patients undergoing major surgeries from the American College of Surgeons' National Surgical Quality Improvement Program database between 2008 and 2011. Demographics, pre- and perioperative risk factors, as well as 30-day morbidities, both overall and specific, were reviewed. The 30-day mortality data were also assessed. Multivariate logistic regression analyses, basic (Adj1) and extended (Adj2), were used to assess the association between gender and outcomes. Out of 1,409,131 patients, 57.2 per cent were females. Females had lower prevalence of most system-specific risk variables. Overall morbidities were also lower in females versus males, even after adjustment for variables [total overall morbidity: ORadj2 = 0.9 (0.89-0.92), P < 0.0001] except in some cases such as after cardiac surgeries [ORadj2 = 1.29 (1.14-1.44), P < 0.0001] and vascular surgeries [ORadj2 = 1.14 (1.10-1.18), P < 0.0001], where overall morbidities of females were higher. Specific morbidities were also lower in females than in males in all types of complications except central nervous system-related postoperative complications [ORadj2 = 1.15 (1.08-1.22), P < 0.0001] and return to the operating room [ORadj2 = 1.06 (1.04-1.08), P < 0.0001]. The 30-day mortality rate for females was lower than males [ORadj2 = 0.99 (0.96-1.03), P = 0.94]. Female gender was associated with less perioperative morbidity and mortality versus males, but they did worse after cardiovascular procedures and had more central nervous system-related complications. These outcomes should be taken into consideration by surgeons and should be evaluated further in future studies.


"Boosting" in Paralympic athletes with spinal cord injury: doping without drugs.
The intentional activation of autonomic dysreflexia (AD, also called "boosting"), a practice sometimes used by athletes affected by spinal cord injury (SCI), is banned by the International Paralympic Committee (IPC). Although various studies have addressed doping and AD as separate issues, studies evaluating AD as a doping method are lacking. The aim of this brief review is to contribute to better understanding of the relationship between doping and AD. We conducted a literature search of the PubMed database (from 1994 onwards). The key search terms "autonomic dysreflexia" and "boosting" were crossreferenced with "sport performance". The official Paralympic website was also viewed. AD is a potent sympathetic reflex, due to a massive release of noradrenaline, that results in marked vasoconstriction distal to the level of the lesion. Athletes with SCI often self-inflict physical suffering in order to induce this phenomenon, which carries high health risks (i.e., hypertension, cerebral hemorrhage, stroke and sudden death). Boosting is a practice that can be compared to doping methods and the IPC expressly prohibits it. Any deliberate attempt to induce AD, if detected, will lead to disqualification from the sporting event and subsequent investigation by the IPC Legal and Ethics Committee.


Synthesis of 4-arylcoumarins via Cu-catalyzed hydroarylation with arylboronic acids.
In the presence of 2-4 mol % of CuOAc, methyl phenylpropiolates having a MOM-protected hydroxy group at the ortho position underwent hydroarylation with various arylboronic acids in MeOH at ambient temperature, resulting in the formation of 4-arylcoumarins in high yields after the acidic workup. This method was effectively used for the synthesis of biologically active natural and artificial compounds.


The effects of methyl internal rotation and (14)N quadrupole coupling in the microwave spectra of two conformers of N,N-diethylacetamide.
The gas phase structures and internal dynamics of N,N-diethylacetamide were determined with very high accuracy using a combination of molecular beam Fourier-transform microwave spectroscopy and quantum chemical calculations at high levels. Conformational studies yielded five stable conformers with C1 symmetry. The two most energetically favorable conformers, conformer I and II, could be found in the experimental spectrum. For both conformers, quadrupole hyperfine splittings of the (14)N nucleus and torsional fine splittings due to the internal rotation of the acetyl methyl group occurred in the same order of magnitude and were fully assigned. The rotational constants, centrifugal distortion constants as well as the quadrupole coupling constants of the (14)N nucleus were determined and fitted to experimental accuracy. The V3 potentials were found to be 517.04(13) cm(-1) and 619.48(91) cm(-1) for conformer I and II, respectively, and compared to the V3 potentials found in other acetamides. Highly accurate CCSD(T) and DMC calculations were carried out for calculating the barriers to internal rotation in comparison with the experimentally deduced V3 values.


Emerging therapeutics in pulmonary hypertension.
Pulmonary hypertension (PH) is a progressive and often fatal illness presenting with nonspecific symptoms of dyspnea, lower extremity edema, and exercise intolerance. Pathologically, endothelial dysfunction leads to abnormal intimal and smooth muscle proliferation along with reduced apoptosis, resulting in increased pulmonary vascular resistance and elevated pulmonary pressures. PH is subdivided into five World Health Organization groups based on the disease pathology and specific cause. While there are Food and Drug Administration-approved medications for the treatment of pulmonary arterial hypertension (PAH; Group 1 PH), as well as for chronic thromboembolic PH (Group 4 PH), the morbidity and mortality remain high. Moreover, there are no approved therapies for other forms of PH (Groups 2, 3, and 5) at present. New research has identified molecular targets that mediate vasodilation, anti-inflammatory, and antifibrotic changes within the pulmonary vasculature. Given that PAH is the most commonly studied form of PH worldwide and because recent studies have led to better mechanistic understanding of this devastating disease, in this review we attempt to provide an updated overview of new therapeutic approaches under investigation for the treatment of PH, with a particular focus on PAH, as well as to offer guidelines for future investigations.


Do the binding properties of oligosaccharides in milk protect human infants from gastrointestinal bacteria?
The oligosaccharide fraction of human milk, the third most abundant solid constituent, consists of hundreds of structures, many of them fucosylated. Oligosaccharides may bear structural homology to cell surface glycoconjugates used as receptors by pathogens, thus protecting nursing infants. The ability of human milk to protect against heat-stable enterotoxin of Escherichia coli in suckling mice has been attributed to neutral fucosylated oligosaccharides of milk. The same phenomenon has been found in human T84 cells, allowing the mechanism of inhibition by the oligosaccharide to be studied in vitro. The oligosaccharide binds to the extracellular domain of guanylyl cyclase, thereby inhibiting the binding of stable toxin. The protective oligosaccharide is a large structure present in too low a concentration to be routinely measured directly; however, its concentration in milk may be inferred by measuring smaller, more plentiful, structurally homologous oligosaccharides. The adhesion by invasive pathogenic strains of Campylobacter to their enterocyte target is also inhibited by human milk fucosyloligosaccharides. Because Campylobacter binds H-2 type oligosaccharide structures, the concentration of protective oligosaccharide may also be inferred from the total oligosaccharide profile. The relationship between oligosaccharide profile heterogeneity in human milk and the incidence of specific gastrointestinal bacterial disease in infants consuming these milks could indicate the significance of these oligosaccharides to infant health. The efficacy of synthetic analogs of active oligosaccharides will confirm their clinical relevance and define minimum structural features essential for activity.