Supercritical water co-oxidation behavior in the different monohydric alcohol-ammonia reaction environment.
The degradation of ammonia is a key rate-limiting step during the supercritical water oxidation of nitrogen-containing organics. This paper studied the co-oxidation behavior between different ammonia-alcohol environments, including the influence of reaction parameters and the co-oxidation mechanism. The results showed that increasing temperature, oxidation coefficient, residence time, and alcohol concentration significantly promoted the degradation of NH3-N and TOC, while rising the ammonia concentration enhanced the NH3-N destruction but inhibited the TOC degradation. Alcohols were oxidized first in the co-oxidation system to produce more OH* and HO2* radicals. Ethanol generated the highest concentration of HO2* in the shortest time, leading to more significant ammonia removal than isopropanol and methanol; however, the produced intermediate products like aldehydes and ketones reacted with residual ammonia to generate a small amount of organics at lower temperatures, inhibiting the degradation of alcohols slightly, and combined catalyst or nitrate in the batch reactor or used continuous supercritical water oxidation or supercritical hydrothermal combustion system without controlling the exotherm of fuels could improve this.


Photometric measurement of color changes in livor mortis as a function of pressure and time. Development of a computer-aided system for measuring pressure-induced blanching of livor mortis to estimate time of death.
Until now, blanching of livor mortis in estimating time of death has generally been assessed based on subjective impressions, i.e. on whether blanching is visible after the application of pressure. We have developed a measuring system that uses digital processing to objectify the relationship between the pressure applied and blanching of postmortem lividity. The pressure is electronically registered by a strain gauge. At predefined levels (10, 20, 30, up to 100 N) the software triggers a color measurement by a commercially available tristimulus colorimeter. All parameters are measured in a single procedure and routed to the computer through a data interface. The pressure-induced color changes in the livor mortis are evaluated according to the L*, a*, b* system (CIE-LAB according to DIN 5033, DIN 6174), which closely approximates the physiology of sight. An additional color spacing formula (delta E) allows analysis of color changes irrespective of the basic skin tone. Initial measurements on cadavers showed that application of increasing pressure produced regular courses of color changes in livor mortis.


The diabetic foot. General considerations and proposal of a new therapeutic and preventive approach.
The treatment of the diabetic foot is a common and sometimes difficult problem. The treatment of the characteristic lesions of the diabetic foot involves many forms of therapy: these include contact dressings and topical treatments. The different therapies that have been applied do not often give satisfactory results. Therefore, for this purpose, we have studied the effect of biostimulation of wound-healing by utilising the CO2 laser together with the action of the KTP laser on 25 patients (11 females and 14 males), all suffering from diabetes mellitus with polyneuropathic ulcers of the foot. Low out-put laser irradiation may stimulate granulation tissue and collagen production in fibroblasts. Many studies observed a regeneration of microcirculation in the ulcer and a regeneration of lymphatic circulation. The laser irradiation method produces a sterilizing effect from bacteria that over-infect the diabetic ulcer too. Each patient underwent a surgical treatment of the edges of the ulcers with CO2 and KTP laser (wavelength 532 nm) focused, and a combined phototherapy (CO2 laser and afterwards KTP laser, defocused). The irradiation was carried out through laser beam (by optic fiber for KTP) manually directed, until all of the ulcer surface became irradiated. On the skin around the ulcer, an omental derived cream (fractionated porcine omental lipid extracts) was daily applied, independently from the laser treatment, to evaluate the angiogenic effect of this substance.(ABSTRACT TRUNCATED AT 250 WORDS)


Impairment of testes development in Yangzhou ganders by augmentation of leptin receptor signaling.
The aim of this study was to determine the cellular and molecular mechanisms of leptin (LEP) and the leptin receptor (LEPR) in testicular development of prepubertal ganders. In an in vivo animal experiment, active immunization against LEPR severely depressed prepubertal testicular development by significantly reducing testicular weights at 200 and 227 days of age. The number of elongated spermatids in the seminiferous tubules was also significantly decreased by immunization with LEPR at ages of 200 and 227 days. Inhibition of testicular development by LEPR immunization was associated with decreases in LHR, StAR, 3β-HSD, CYP11A1, CYP17A1, and PRLR mRNA expression levels in testicular tissue, which resulted in a significant decrease in testosterone synthesis. In the in vitro experiments, the addition of LEP combined with anti-LEPR antibodies strengthened LEPR signal transduction, and inhibited significantly testosterone production in cultured Leydig cells isolated from prepubertal gander testes. The mRNA expression of LHR, StAR, 3β-HSD, CYP11A1, CYP17A1 also decreased significantly after treatment with LEP combined with anti-LEPR antibodies in cultured Leydig cells. These results suggest that anti-LEPR antibodies strengthen LEPR signaling transduction in the presence of LEP, and immunization against LEPR inhibited testes development and testosterone secretion in prepubertal ganders.


Changes in histopathological classification of neuroendocrine tumors in 5th edition of WHO classification of gastrointestinal tract tumors (2019).
In a brief review is presented a summary of news in the classification of neuroendocrine neoplasms of the digestive system, as they were introduced in the 5th edition of the WHO Classification of Digestive System Tumors published in summer 2019.


[Determination of hyperin in genus Hypericum medicinal plants].
To compare the content of hyperin in Hypericum medicinal plants. HPLC method was established. Alltima C18 radial compression column was used with a mobile phase of methanol-0.5% phosphoric acid (45:55, adjusted to pH = 3.0 with triethylamine). The detecting wavelength was 360 nm. Flow rate was 0.8 ml/min, external standard method was quantitative analysis method. The linear range was 0.101-2.023 microg. The average recovery was 96.527%. The result showed that the content of hyperin in H. perforatum, H. forrestii was higher than that of others (1.257% and 0.461% respectively). This method provides an accurate and sensitive way in detecting hyperin.


In vivo phage display to identify new human antibody fragments homing to atherosclerotic endothelial and subendothelial tissues [corrected].
In vivo phage display selection is a powerful strategy for directly identifying agents that target the vasculature of normal or diseased tissues in living animals. We describe here a new in vivo biopanning strategy in which a human phage single-chain antibody (scFv) library was injected into high-fat diet-fed ApoE(-/-) mice. Extracellular and internalized phage scFvs were selectively recovered from atherosclerotic vascular endothelium and subjacent tissues. After three successive biopanning rounds, a panel of six clones with distinct gene sequences was isolated. Four scFvs produced and purified in soluble form were shown to interact in vitro with a rabbit atheromatous protein extract by time-resolved fluorescence resonance energy transfer and to target the endothelial cell surface and inflamed intima-related regions of rabbit and human tissue sections ex vivo. These new scFvs selected in a mouse model recognized both rabbit and human tissue, underlying the interspecies similarities of the recognized epitopes. By combining immunoprecipitation and mass spectrometry, one of the selected scFvs was shown to recognize carbonic anhydrase II, an up-regulated enzyme involved in resorption of ectopic calcification. These results show that in vivo biopanning selection in hypercholesterolemic animals makes it possible to identify both scFvs homing to atherosclerotic endothelial and subendothelial tissues, and lesion-associated biomarkers. Such scFvs offer promising opportunities in the field of molecular targeting for the treatment of atherosclerosis.


Haemophilia care in Europe - A survey of 37 countries.
The European Haemophilia Consortium (EHC) is an international non-profit organization representing 45 national patients' organizations in Europe. Every 3 years, the EHC circulates a survey to its national member organizations to assess the state of haemophilia care. The purpose of this exercise is to ascertain information about the organization of haemophilia care and treatment availability at national levels. Furthermore, the survey provides a basis from which the EHC are able to monitor the unmet need and stability of care/treatment access in the individual member countries. Surveys are distributed to EHC member organizations in English and Russian. Patient organizations are encouraged to share the survey with local clinicians to ensure accuracy of responses. The data collected are in part consistent to provide a longitudinal overview for treatment access, but topical items are included such as ageing. Subsequently, completed surveys are transposed into a database for analysis and reporting. Thirty-seven responses were received from the 45 countries approached, representing an 82% response rate from members. Findings suggest increased access to treatment and some improvement in certain areas of care. However, access to treatment has declined or remained largely unchanged in some countries. The survey has been a successful exercise in enabling a greater understanding of the current Haemophilia care landscape across Europe. However, there remain unmet needs in various aspects of patient care, and specific examples include psychosocial care and general preparedness for an ageing haemophilia population.


Selecting Multiple Node Statistics Jointly from Functional Connectivity Networks for Brain Disorders Identification.
Functional connectivity networks (FCN) analysis is instructive for the diagnosis of brain diseases, such as mild cognitive impairment (MCI) and major depressive disorder (MDD) at their early stages. As the critical step of FCN analysis, feature representation provides the basis for finding potential biomarkers of brain diseases. In previous studies, different node statistics (e.g. local efficiency and local clustering coefficients) are usually extracted from FCNs as features for the diagnosis/classification task, which can specifically locate disease-related regions on the node level, so as to help us understand the neurodevelopmental roots of brain disorders. However, each node statistic is proposed only considering a kind of specific network property, which has one-sidedness and limitations. As a result, it is incomplete to represent a node with only one statistic. To resolve this issue, we put forward a novel scheme to select multiple node statistics jointly from the estimated FCNs for automated classification, called multiple node statistics feature selection (MNSFS). Specifically, we first extract multiple statistics from the same nodes and assign each kind of statistic into a group. Then, sparse group least absolute shrinkage and selection operator (sgLASSO) is used to select groups (nodes) and statistics in the groups towards a better classification performance. Such a technique enables us to simultaneously locate the discriminative brain regions, as well as the specific statistics associated with these brain regions, making the classification results more interpretable. We conducted our scheme on two public databases for identifying subjects with MCI and MDD from normal controls. Experimental results show that the proposed scheme achieves superior classification accuracy and features interpreted on the benchmark datasets.


Viral antibodies in serum and cryoprecipitate of patients with essential mixed and secondary cryoglobulinemia. Preliminary results.
Antibodies to measles virus, CMV, HSV1, HSV2 and EBV have been tested in 9 patients with essential mixed cryoglobulinemia (EMC) and 24 patients with cryoglobulinemia associated with lymphoproliferative, autoimmune or hepatic diseases (secondary cryoglobulinemia, SC). The assays were performed in serum, cryoprecipitate and supernatant by using immunoenzymatic methods. The highest prevalence was observed in the supernatant of both EMC and SC patients. Antibodies to measles virus show a serum/cryoprecipitate ratio higher than that of the other viral agents. Statistically significant differences between EMC and SC patients in the positivity of the various viral antibodies were not shown.


Discoid lupus in antiphospholipid syndrome: case description and literature review.
The aim of the study was to report about a patient with discoid lupus erythematosus (DLE) who developed antiphospholipid syndrome (APS) 12 years after DLE diagnosis and review related literature. This is a case report of a 34-year-old woman with DLE who developed APS. A review of articles published in the PubMed/MEDLINE, LILACS, and SciELO databases from 1966 to October 2020 was conducted using the following search terms: "antiphospholipid syndrome," "antiphospholipid antibodies," and "discoid lupus erythematosus" No language limitation was applied. Besides the present case, 5 case reports were identified. One case-control and two cross-sectional studies on antiphospholipid antibodies with or without APS in DLE were also reviewed. These studies revealed that APS can develop even 37 years after DLE was diagnosed. The case-control study found that patients with DLE have more anticardiolipin antibodies than controls. In contrast, one cross-sectional study showed a low prevalence of antiphospholipid antibodies in their group of patients, which was similar to findings in the general population. This study reviewed previous articles on DLE cases associated with antiphospholipid antibodies and/or APS, adding a new case description.


Evaluation of an animal protein-free semen extender for cryopreservation of epididymal sperm from North American bison (Bison bison).
The objective was to evaluate the suitability of an animal protein-free semen extender for cryopreservation of epididymal sperm from the two subspecies of North American bison: plains (Bison bison bison) and wood (Bison bison athabascae) bison. Both cauda epididymides (from six plains and five wood bison) were minced and incubated in Sp-TALPH buffer for approximately 2 h at 37 °C to release actively motile sperm. Sperm suspensions were filtered, centrifuged and the sperm pellet from each bull was divided into two fractions and diluted either in egg yolk containing extender, Triladyl, or in an animal protein-free extender, Andromed, and equilibrated for 20 min at 37 °C. Thereafter, samples were chilled and cryopreserved. Frozen-thawed sperm were evaluated for motility (computer assisted sperm analysis), viability (SYBR 14 and propidium iodide), acrosome integrity (FITC conjugated PSA), cryocapacitation (tyrosine phosphorylation of sperm proteins as a biomarker), and fertilizing ability (in a heterologous IVF system). There was no significant difference for progressive motility, viability, and acrosome integrity between the two extenders for plains bison (36.8 ± 9.0, 60.5 ± 17.4, and 77.3 ± 4.6%; overall mean ± SD) as well as for wood bison (11.7 ± 8.1, 13.7 ± 5.6, and 73.4 ± 4.2%). Levels of tyrosine phosphorylation did not differ for sperm preserved in the two extenders for both subspecies, although an inter-bull variability in the response to tyrosine phosphorylation between extenders was suggested for plains bison. Fertilization percent did not differ significantly between extenders for plains bison (84.16 ± 9.92%, overall mean ± SD) and for wood bison (59.53 ± 19.99%). In conclusion, in the absence of significant difference between extenders in post-thaw sperm characteristics, we inferred that Andromed (animal protein-free) was suitable for cryopreservation of epididymal sperm from North American bison.


Evaluation of image processing technique and discriminant analysis methods in postharvest processing of carrot fruit.
The most important process before packaging and preserving agricultural products is sorting operation. Sort of carrot by human labor is involved in many problems such as high cost and product waste. Image processing is a modern method, which has different applications in agriculture including classification and sorting. The aim of this study was to classify carrot based on shape using image processing technique. For this, 135 samples with different regular and irregular shapes were selected. After image acquisition and preprocessing, some features such as length, width, breadth, perimeter, elongation, compactness, roundness, area, eccentricity, centroid, centroid nonhomogeneity, and width nonhomogeneity were extracted. After feature selection, linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) methods were used to classify the features. The classification accuracies of the methods were 92.59 and 96.30, respectively. It can be stated that image processing is an effective way in improving the traditional carrot sorting techniques.


Oncological Safety of Autologous Fat Grafting in Breast Reconstruction after Mastectomy for cancer: A case-control study.
The use of autologous fat grafting in the context of breast reconstruction is still a matter of controversy. The objective of this study was to compare the local relapse rate in women who had a fat grafting session in the context of breast reconstruction after breast cancer management, to those who had breast reconstruction without fat grafting. We performed a retrospective, monocentric, case-control study from January 2007 to December 2017 in our hospital. The cases included women who underwent breast reconstruction with autologous fat grafting and controls, undergoing breast reconstruction without fat grafting. We compared survival and local recurrence between the two groups. 412 women were included: 109 (26.5%) in the lipofilling group and 303 women (73.5%) in the "no lipofilling" group. In the overall study population, lipofilling did not appear to be a predictive factor for recurrence, HR = 1.39 [0.63 - 3.06], p = 0.41; or a predictive factor for overall survival, HR = 0.84 [0.23 - 3.02], p = 0.79, or for distant metastases, HR = 1.10 [0.43 - 2.79], p = 0.84. In contrast, in the subgroup of women treated for invasive cancer, the multivariate analysis showed that lipofilling in this context was an independent predictive factor for local recurrence (HR= 5.06 [1.97 - 10.6], p = 0.04). we found an increased risk of local recurrence after lipofilling in women who were managed for invasive breast cancer. This suggests that special consideration should be given to women who have had invasive breast cancer before lipofilling.


Disparities in Pediatric Patient Portal Activation and Feature Use.
Disparities in adult patient portal adoption are well-documented; however, less is known about disparities in portal adoption in pediatrics. This study examines the prevalence and factors associated with patient portal activation and the use of specific portal features in general pediatrics. We analyzed electronic health record data from 2012 to 2020 in a large academic medical center that offers both parent and adolescent portals. We summarized portal activation and use of select portal features (messaging, records access and management, appointment management, visit/admissions summaries, and interactive feature use). We used logistic regression to model factors associated with patient portal activation among all patients along with feature use and frequent feature use among ever users (ie, ≥1 portal use). Among 52 713 unique patients, 39% had activated the patient portal, including 36% of patients aged 0-11, 41% of patients aged 12-17, and 62% of patients aged 18-21 years. Among activated accounts, ever use of specific features ranged from 28% for visit/admission summaries to 92% for records access and management. Adjusted analyses showed patients with activated accounts were more likely to be adolescents or young adults, white, female, privately insured, and less socioeconomically vulnerable. Individual feature use among ever users generally followed the same pattern. Our findings demonstrate that important disparities persist in portal adoption in pediatric populations, highlighting the need for strategies to promote equitable access to patient portals.


Scleredema diabeticorum successfully treated with ultraviolet A1 phototherapy.
Scleredema diabeticorum is an uncommon condition. It is one of the cutaneous manifestations in diabetes mellitus that mainly occurs in obese middle-aged men with insulin-resistant diabetes. This condition is generally recalcitrant to therapy. Various treatments have been tried with inconsistent results. Here, we describe two cases of scleredema diabeticorum with substantial clinical improvement from a course of medium dose (60 J/cm²) ultraviolet A1 radiation therapy.


Methylation and microsatellite status and recurrence following adjuvant FOLFOX in colorectal cancer.
The prognostic impact of CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) on the treatment outcome of colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) is unclear. We investigated CIMP and MSI status in colorectal cancer patients treated with adjuvant FOLFOX. Stages II and III sporadic colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Eight CpG island loci (CACNA1G, CRABP1, IGF2, MLH1, NEUROG1, CDKN2A (p16), RUNX3 and SOCS1) and five microsatellite markers were examined. Disease-free survival (DFS) was analyzed according to CIMP and MSI status. A total of 322 patients were included: male/female 192/130, median age 61 years (range 30-78), proximal/distal location 118/204 and Stages II/III 43/279. CIMP status was high in 25 patients (7.8%) and 21 patients (6.5%) had MSI-high tumor. CIMP/MSI status was not significantly associated with DFS: 3-year DFS 100% in CIMP(-)/MSI(+), 84% in CIMP(-)/MSI(-), 82% in CIMP(+)/MSI(-) and 75% in CIMP(+)/MSI(+) (p = 0.33). Results of exploratory analysis showed that concurrent methylation at NEUROG1 and CDKN2A (p16) was associated with shorter DFS: 3-year DFS 69% in NEUROG1(+)/CDKN2A (p16)(+) versus 87% in NEUROG1(-)/CDKN2A (p16)(-) (p = 0.006). In conclusion, concurrent methylation of NEUROG1 and CDKN2A (p16) is associated with recurrence following adjuvant FOLFOX in Stages II/III colorectal cancer.


Rapid parallel semantic processing of numbers without awareness.
In this study, we investigate whether multiple digits can be processed at a semantic level without awareness, either serially or in parallel. In two experiments, we presented participants with two successive sets of four simultaneous Arabic digits. The first set was masked and served as a subliminal prime for the second, visible target set. According to the instructions, participants had to extract from the target set either the mean or the sum of the digits, and to compare it with a reference value. Results showed that participants applied the requested instruction to the entire set of digits that was presented below the threshold of conscious perception, because their magnitudes jointly affected the participant's decision. Indeed, response decision could be accurately modeled as a sigmoid logistic function that pooled together the evidence provided by the four targets and, with lower weights, the four primes. In less than 800ms, participants successfully approximated the addition and mean tasks, although they tended to overweight the large numbers, particularly in the sum task. These findings extend previous observations on ensemble coding by showing that set statistics can be extracted from abstract symbolic stimuli rather than low-level perceptual stimuli, and that an ensemble code can be represented without awareness.


Prevention of transmission of multidrug-resistant organisms during catheter exchange using antimicrobial catheters.
Exchanging a central venous catheter (CVC) over a guide wire for a fresh uncoated CVC in the presence of bacteremia can result in cross-infection of the newly exchanged CVC. A recent retrospective clinical study showed that exchanging a catheter over a guide wire in the presence of bacteremia using an antimicrobial minocycline-rifampin (M/R) catheter may improve outcomes. To expand on this, we developed an in vitro cross-contamination model of exchange to evaluate the efficacy of different antimicrobial CVCs in preventing cross-contamination of multidrug-resistant organisms during exchange. Uncoated CVCs were allowed to form biofilm by methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. After 24 h, the biofilm-colonized CVCs were placed in a glass tube containing bovine calf serum plus Mueller-Hinton broth, and each catheter was exchanged over a guide wire for a fresh uncoated or an M/R-, chlorhexidine-silver sulfadiazine (CHX/SS)-, or chlorhexidine-M/R (CHX-M/R)-coated CVC. Cross-contamination of exchanged catheters was enumerated by sonication and quantitative plating methods. The exchange of M/R CVCs completely prevented cross-contamination by MRSA biofilms compared to control exchanged CVCs (P<0.0001). Exchange with CHX/SS CVCs reduced but did not completely prevent cross-contamination by MRSA (P=0.005). Exchange with CHX-M/R CVCs completely prevented cross-contamination by MRSA, P. aeruginosa, and C. albicans biofilms (P<0.0001). Furthermore, CHX-M/R CVCs were superior to M/R CVCs against P. aeruginosa and C. albicans (P=0.003) and were superior to CHX/SS CVCs against MRSA and P. aeruginosa (P=0.01). In conclusion, exchange with the novel CHX-M/R CVC was the only exchange effective in completely and concurrently preventing cross-contamination from bacteria and Candida.


The effect of cyanide intoxication on hepatic rhodanese kinetics.
1. Results of studies on the kinetics of hepatic rhodanese and the effects of S-adenosyl-L-methionine (SAM) on these kinetic parameters in cyanide-treated and non-treated mice are reported here. 2. The enzyme exhibited typical Michaelis-Menten behaviour with cyanide inhibition at concentrations higher than 50 mM. Km values of 4.74 and 0.85 mM were obtained for thiosulphate and cyanide, respectively, in control mice. 3. These results stress the biological importance of the rhodanese reaction for cyanide detoxification. 4. Km values were not significantly modified when the animals were intoxicated with a lethal (20 mg/kg) or a non-lethal (4 mg/kg) dose of cyanide. 5. SAM treatment either in control or in cyanide-poisoned animals doubled the Km's for cyanide.


Beyond muscular effects: depression of spinal recurrent inhibition after botulinum neurotoxin A.
The natural target of the botulinum neurototoxin type A (BoNT-A) is the neuromuscular junction. When injected into a muscle, BoNT-A is internalized by motoneurone terminals where it functions as an endopeptidase, cleaving protein components of the synaptic machinery responsible for vesicle docking and exocytosis. As a result, BoNT-A induces a characteristic flaccid paralysis of the affected muscle. In animal models, BoNT-A applied in the periphery can also influence central activity via retrograde transport and transcytosis. An analogous direct central effect in humans is still debated. The present study was designed to address whether BoNT-A modifies the activity of the spinal recurrent inhibitory pathways, when injected at muscular level, in humans. To avoid methodological bias, the recurrent inhibition from an injected muscle (soleus) was investigated on an untreated muscle (quadriceps), and stimulation parameters (producing recurrent inhibition) were monitored on a third non-injected muscle but innervated by the same nerve as the soleus (flexor digitorum brevis). The experiments were performed on 14 post-stroke patients exhibiting spasticity in ankle plantarflexors, candidates for BoNT-A. One month after BoNT-A, the level of recurrent inhibition was depressed. It is suggested that the depression of recurrent inhibition was induced by BoNT-A, injected peripherally, through axonal transport and blockade of the cholinergic synapse between motoneurone recurrent collaterals and Renshaw cells.


Uncovering quality markers of Yiqi-Tongluo capsule against myocardial ischemia and optimization of its extraction process.
Myocardial ischemia (MI), a condition in which the heart is unable to function due to insufficient blood and oxygen supply, is a major cause of death from coronary heart disease (CHD). Yiqi Tongluo capsule (YTC) is a Chinese patent drug which commonly used for treatment of MI in clinic. However, the related active components of YTC for treatment of MI were still uncovered. This paper is aimed to study the quality markers (Q-markers) of YTC and further optimize the extraction process of YTC based on Q-markers, providing research foundation for the further modern pharmaceutical preparations of YTC. We firstly used UPLC-QTOF-MS to analyze the constituents of YTC absorbed in blood, then isoprenaline (ISO) induced H9c2 cell model was used further screen the active constituents with protective effects on cardiomyocytes. After that, the orthogonal table (L9 (34)) was used to optimize the extraction process with three levels of 4 factors (water addition, immersion time, extraction time and decoction times). Finally, the HPLC fingerprint of 15 batches of optimized YTC was established. In our present study, a total of 33 components were identified in YTC, of which 10 components were absorbed in blood. Among the 10 components, 8 compounds had significant protective effects on ISO stimulated H9c2 cells, including Paeoniflorin, Ferulic acid, Calycosin, Senkyunolide A, N-butylphthalide, Z-ligustilide, LevistilideA, and Astragaloside IV, which were considered as the Q-markers of YTC. The optimized extraction process based on Q-marker as follows: soaking 1 h, then adding 8 times water to extract 3 times by decoction, each extraction lasts 1.5 h. The HPLC fingerprint of optimized YTC was established with 15 batches of YTC samples, and the optimized YTC samples has no significant toxicity to the heart, liver, spleen, lungs, and brain tissues of rats.


Saturated fatty acids recognition by the CD14-TLR4-MD2 complex may engage in the presurgical anxiety-induced persistent postsurgical pain.
It has been proved that presurgical anxiety can induce the development and progression of persistent postsurgical pain through elevating circulating corticosterone levels and activating the glucocorticoids receptor. Under stressful circumstances, the concentration of blood saturated fatty acids (SFAs) increases rapidly to provide enough ATP for individuals' survival owing to stress hormones such as glucocorticoid, catecholamine and glucagon. It is reported that SFAs can trigger an inflammatory response through CD14-TLR4-MD2 complex. The role of TLR4 and its downstream signaling pathway has been confirmed in the pathogenesis of cancer pain and inflammatory pain. Furthermore, a newly clinical research uncovers that the children with recurrent abdominal pain, which is triggered by early psychosomatic stress, have higher levels of SFAs than healthy individuals. We therefore put forward the hypothesis that the elevated level of SFAs induced by stress hormones may be engaged in the presurgical anxiety-induced persistent postsurgical pain. If established, it's of important clinical significance, which will make great contributions to the prevention and treatment of the presurgical anxiety-induced persistent postsurgical pain.


Sand sorption process for the removal of sodium dodecyl sulfate (anionic surfactant) from water.
Granite sand was used to adsorb anionic surfactant, sodium dodecyl sulfate (SDS) from water at natural pH 6.25. The effect of adsorbent size, pH, temperature and amount of adsorbent has been examined. The results indicate that the Langmuir model provides the best correlation of experimental data. Thermodynamic parameters like entropy, enthalpy and free energy of adsorption were evaluated. Decreasing the temperature accelerates the adsorption of SDS onto sand surface. The kinetic data were analyzed by using pseudo-first order Lagergren equation. Adsorption of SDS was exothermic and dominated by physisorption with activation energy (Ea) 33.65 kJ mol(-1). In addition, regeneration of granite sand by washing with Fenton likes reagent was examined. The results suggested that granite sand is suitable as a sorbent material for recovery and adsorption of SDS from aqueous solutions in view of its effectiveness and cheaper cost.


Disease-Defining Molecular Features of Primary Cutaneous B-Cell Lymphomas: Implications for Classification and Treatment.
Primary cutaneous B-cell lymphoma-primary cutaneous follicle center lymphoma; primary cutaneous marginal zone lymphoma; and primary cutaneous diffuse large B-cell, leg type-is a heterogeneous group with a variety of clinical and histological presentations. Until recently, the molecular bases of these disease subtypes have been unclear. We and others have identified the specific genetic characteristics that distinguish these subtypes from their respective systemic counterparts. These molecular features can improve diagnoses, determine the likelihood of concurrent or future systemic disease, and enable the rational design of novel clinical trials.


Heterogeneity of carnitine-palmitoyltransferase deficiency.
Episodes with muscle ache, rhabdomyolysis and myoglobinuria with or without associated renal insufficiency are characteristic of muscle carnitinepalmitoyltransferase (CPT) deficiency. However, patients differ from each other in many aspects, such as the kind of stimulus that triggers rhabdomyolysis, the ability to produce ketone bodies when fasting, whether the enzyme defect is localized in skeletal muscle or is general, and the nature of the enzyme defect, which may be in CPT I or CPT II or both. Studies of muscle, liver and fibroblasts from a patient with recurrent rhabdomyolysis spontaneously occurring or triggered by exercise or fever, revealed a CPT deficiency in the muscle and liver biopsy samples but normal CPT activity in cultured cells, differing from previously reported patients. The enzyme defect in muscle was evidenced by two different methods, but not when determined with a method that measures the formation of palmitoylcarnitine. The enzyme abnormality in the patient's liver was associated with a delayed ketone body production and with a dramatic increase in long-chain acylcarnitines in the serum when fasting. Moreover the patient was unable to build up ketones when fed long-chain triglycerides (LCT) but showed prompt ketogenic response when fed medium-chain triglycerides (MCT). The heterogeneity of clinical presentations and of the biochemical findings in patients with CPT deficiency are discussed.


The role of ALA-S and ALA-D in regulating porphyrin biosynthesis in a normal and a HEM R+ mutant strain of Saccharomyces cerevisiae.
Catabolite repression and derepression on delta-aminolevulinate synthase (ALA-S) and delta-aminolevulinate dehydratase (ALA-D) in a normal yeast strain, D27, and its derived D27/C6 (HEM R+) were investigated. ALA-S and ALA-D activities and intracellular ALA (I-ALA) at different physiological states of the cells were measured. In YPD medium, under conditions of repression and when glucose was exhausted, both strains behaved identically as if the mutation was not expressed. In YPEt medium, however, both ALA-S and ALA-D activities were higher than in YPD, but the I-ALA content and the enzymic activity profiles shown by the two strains were quite different. It appears, therefore, that the mutation causes a deregulation of ALA-S, so that its activity is kept at a high level throughout the cell cycle. This would explain the increased levels of cytochromes present in the mutant. This mutation may affect some regulatory aspect of ALA formation and renders an ALA-S of high activity; moreover, this enzyme species seems to be more stable than in the normal strain.


Thyrotoxic periodic paralysis in a patient with Graves' disease: A case report.
Thyrotoxic periodic paralysis (TPP) is a rare and often misdiagnosed, hypokalemic periodic paralysis with features of mainly recurrent acute limb weakness with good treatment outcome if diagnosed early. We here report a case of a 25-year-old male with a history of recurrent bilateral upper and lower limbs weakness resolved by potassium infusion later found to have Thyrotoxicosis (Graves' disease). MRI scans of the brain had no abnormal finding while thyroid scintigraphy showed diffuse toxic goiter. Graves' disease shares a majority of TPP while, other causes like toxic adenoma, thyroiditis, toxic multinodular goiter, amiodarone induced thyrotoxicosis, levothyroxine intoxication and thyrotropin (TSH) producing pituitary adenoma are also associated with TPP. The management of thyrotoxicosis by medical therapy, surgery or radioactive iodine therapy is the mainstay of treatment of TPP patients. For the treatment of acute attacks, potassium administration is necessary keeping in mind the problem of hyperkalemia because of excess doses of potassium as it shifts to extracellular space. TPP should be considered as a differential in the cases of limb weakness and the secondary causes especially Thyrotoxicosis and precipitating factors should be identified.


Tumor volume-adapted SUVN as an alternative to SUVpeak for quantification of small lesions in PET/CT imaging: a proof-of-concept study.
SUVpeak is a recommended quantification metric except for small lesions. We aimed to assess the averaged standard uptake value (SUVN) as an alternative to SUVpeak for small-lesion quantification. NEMA-like phantom images were reconstructed using OSEM, OSEM + PSF, OSEM + TOF and OSEM + TOF + PSF with two post-smoothing Gaussian filters for different background activity levels. SUVmax, SUVN (N = 5, 10, 15, 20, 25, 30, 35 or 40 hottest voxels), and SUVpeak, relative percent error, contrast recovery, and volume recovery coefficients were quantified and assessed. SUVN did not have the limitations of SUVpeak for smaller lesions. In the smallest insert at 2.68 kBq/ml, optimum N values for OSEM, OSEM + PSF, OSEM + TOF and OSEM + TOF + PSF were 10, 5, 15, and 10 for SUVN, respectively. The same N values were obtained for metabolic tumor volumes (MTVs) for all reconstruction algorithms. At 5.30 kBq/ml, N = 5 was optimum for SUVN and MTVs. For the larger inserts, the optimum N increased and tended towards the maximum (similar to SUVpeak). SUVN is more accurate than SUVmax or SUVpeak for small lesions, while being as accurate in larger ones. This harmonizing capacity of SUVN can be beneficial for the quantitative analysis of small tumor volumes.


Prolactin receptors on human lymphocytes and their modulation by cyclosporine.
Prolactin receptors have been identified for the first time on human peripheral blood lymphocytes. These receptors are present on T- and B-cells as well as monocytes. The specific binding of [125I]prolactin to these cells can be selectively enhanced at certain concentrations and blocked by higher concentrations of cyclosporine , a known immunosuppressive agent which inhibits the mitogenesis of T-cells. Prolactin also induces ornithine decarboxylase, a key growth regulatory enzyme, in lymphocytes. Therefore, we suggest that the lymphocyte prolactin receptor may be involved in regulating lymphocyte function, and that one of the actions of cyclosporine is to block this rather ubiquitously occurring receptor.


Variability - Surface intensity distribution of large-area reference sources.
In this paper we present the impact of variability, a surface source parameter, on the efficiency evaluation of surface contamination monitors. This study was based on two source uniformity correction methodologies and data from real surface source distributions. Surface source intensity distribution has been changed by rearranging the cells (portions of the active area of each LARS) while keeping the same source uniformity value. Instrument efficiencies have been calculated for different sets of uniformities and variabilities. This study led to emphasize the importance of variability, a differential source intensity distribution parameter, over the uniformity, an integral source intensity distribution parameter, and reinforced the importance of the source uniformity correction procedure on the course of surface contamination monitor calibration.


Rising from the ashes: cellular senescence in regeneration.
Cellular senescence has recently become causally implicated in pathological ageing. Hence, a great deal of research is currently dedicated towards developing senolytic agents to selectively kill senescent cells. However, senescence also plays important roles in a range of physiological processes including during organismal development, providing a barrier to tumorigenesis and in limiting fibrosis. Recent evidence also suggests a role for senescence in coordinating tissue remodelling and in the regeneration of complex structures. Through its non-cell-autonomous effects, a transient induction of senescence may create a permissive environment for remodelling or regeneration through promoting local proliferation, cell plasticity, tissue patterning, balancing growth, or indirectly through finely tuned interactions with infiltrating immune mediators. A careful analysis of the beneficial roles of cellular senescence may provide insights into important physiological processes as well as informing strategies to counteract its detrimental consequences in ageing and disease.


The validation of a newly developed Arabic scale to assess patient-reported side-effects of antineoplastic agents.
Multiple scales in different languages were developed to measure patient-reported side effects of antineoplastics. However, these scales vary in their coverage of antineoplastics' side effects, and none of them address both the severity and impact of antineoplastics' side effects on patient quality of life. Hence, there is a need to develop a comprehensive, concise, and general scale to assess patients' perceptions of both severity and impact of the commonly reported side effects of antineoplastics on patients' activities of daily living and make it available in Arabic. To develop and validate a new scale in Arabic to assess patient-reported antineoplastics' side-effects among Arabic-speaking patients undergoing chemotherapy. A new scale was developed in Arabic that addresses 40 different emotional, cognitive, and physical side-effects of antineoplastics. The Antineoplastic Side effects Scale (ASES) contained three subscales focused on the side effects frequency, severity, and interference with patients' activities of daily living. Seventy-eight patients with different cancer types were recruited from the oncology clinics of a university-affiliated tertiary care hospital in Riyadh, Saudi Arabia. The reliability of the questionnaire was examined using Cronbach's alpha method. The construct validity was examined using principal component analysis with varimax rotation. The association between the scores of ASES subscales and various patient medical and sociodemographic characteristics were also examined. The mean age of participants was 53.8 (12.5) years and most of them were female (65.3%) and married (84.6%). The ASES demonstrated good internal consistency (Cronbach's alpha = 0.91). The severity of the perceived side effects and their impact on activities of daily living were positively associated with female gender. The newly developed ASES demonstrated good validity and reliability. This tool will hopefully help healthcare providers and patients to identify commonly reported antineoplastic side effects.


A guide to Open-JIP, a low-cost open-source chlorophyll fluorometer.
Chlorophyll a fluorescence is the most widely used method to study photosynthesis and plant stress. While several commercial fluorometers are available, there is a need for a low-cost and highly customisable chlorophyll fluorometer. Such a device would aid in performing high-throughput assessment of photosynthesis, as these instruments can be mass-produced. Novel investigations into photosynthesis can also be performed as a result of the user's ability to modify the devices functionality for their specific needs. Motivated by this, we present an open-source chlorophyll fluorometer based on the Kautsky induction curve (OJIP). The instrument consists of low-cost, easy-to-acquire electrical components and an open-source microcontroller (Arduino Mega) whose performance is equivalent to that of commercial instruments. Two 3D printable Open-JIP configurations are presented, one for higher plants and the other for microalgae cells in suspension. Directions for its construction are presented and the instrument is benchmarked against widely used commercial chlorophyll fluorometers.


Stage and lineage-regulated expression of two hsp90 transcripts during mouse germ cell differentiation and embryogenesis.
The expression of members of the heat shock protein 90 (hsp90) gene family during testicular and embryonic development was investigated. Two different hsp90 transcripts were detected in RNA from mouse testis, approximately 3.2 kb and 2.9 kb in size, and were shown to exhibit cellular and developmental stage specificity of expression. The larger, more abundant transcript was expressed at high levels in the germinal compartment of the testis, particularly in germ cells in meiotic prophase. The smaller hsp90 transcript was expressed predominantly in the somatic compartment of the testis. Expression of the two hsp90 transcripts was observed in testes of other species, suggesting an important role for hsp90 in mammalian testicular function. In addition, expression of both hsp90 transcripts was detected in the embryonic and extra-embryonic compartments of mid-gestation embryos.


α4β7 Integrin expression and blockade in pediatric and young adult gastrointestinal graft-versus-host disease.
We hypothesized that α4β7 integrin expression on effector memory T cells (TEMs) would be elevated in pediatric hematopoietic stem cell transplant (HSCT) patients before and at diagnosis of acute gastrointestinal graft-versus-host disease (GI GVHD) symptoms compared to patients without GVHD, and that clinical blockade of α4β7 integrin with vedolizumab would be effective in pediatric GI GVHD. We analyzed surface expression of α4β7 integrin on T cells from 48 pediatric allogeneic HSCT recipients from our biorepository with known clinical outcomes as follows: acute GI GVHD (n = 22), isolated skin GVHD (n = 12), and no GVHD (n = 14). T-cell analyses were performed 1 week before and at GVHD diagnosis in patients with GVHD, and day +30 after HSCT in patients without GVHD. We describe clinical outcomes of seven additional patients, different from above-described 48 patients, who received vedolizumab (anti-α4β7 integrin antibody) for the treatment of steroid-refractory acute GI GVHD. Expression of α4β7 integrin on CD8+ TEMs was upregulated in patients with GI GVHD compared to the no GI GVHD (skin GVHD + no GVHD) group 1 week prior to clinical symptoms (p = .02) and at acute GI GVHD diagnosis (p = .05). Four of seven treated patients with clinical steroid-refractory acute GI GVHD were evaluable for response to vedolizumab. One patient had a complete response at day +28, while two had a partial response, and one had no response. No adverse effects directly attributable to vedolizumab were observed. Our data suggest a rationale for the blockade of α4β7 integrin for acute GI GVHD management in children.


Increased interleukin-6 production by cerebral cortical tissue of adult versus young mice.
The cytokine interleukin-6 (IL-6) has been implicated as a contributor to injury in several neurological disorders. The amounts of IL-6 released by the cerebral cortical tissue of mice of varying maturational age groups were measured and found to increase with age. Specifically, the basal level of IL-6 released from the tissue of infant (less than 2 weeks old) mice was low, although the tissue could be readily stimulated to secrete high levels of IL-6. Higher levels of IL-6 were released from young adult (2 month old) mice. Adult mice that were either 6 or 9 months of age secreted significantly higher levels of IL-6 compared to the tissue of either the young adult or infant animals, although the difference between levels secreted by the 6- or 9-month old groups was minimal. IL-6 production by adult cerebral cortical tissue could be further stimulated, but it was less readily achieved compared to the tissue of infants. In response to the negative regulator transforming growth factor-beta (TGF-beta), the levels of IL-6 released by stimulated cerebral cortical tissue of infants, as well as by unstimulated and stimulated tissue of adults, were reduced to the low basal levels of IL-6 produced by infant tissue. These results suggest that normal development and aging are correlated with an increase in IL-6 production that may be due to shifts in levels of stimulatory or inhibitory regulatory controls, but not to an inability of young tissue to produce IL-6 or to a lack of responsiveness of adult tissue to negative regulatory control by TGF-beta.


Cryo-electron tomography of homophilic adhesion mediated by the neural cell adhesion molecule L1.
The neural cell adhesion molecule L1 participates in homophilic interactions important for axon guidance and neuronal development. The structural details of homophilic adhesion mediated by L1 and other immunoglobulin superfamily members containing an N-terminal horseshoe arrangement of four immunoglobulin-like domains are unknown. Here we used cryo-electron tomography to study liposomes to which intact or truncated forms of the L1 ectodomain were attached. Tomographic reconstructions revealed an adhesion interface with a regular and repeating pattern consistent with interactions between paired horseshoes contributed by L1 proteins from neighboring liposomes. The characteristics of the pattern changed when N-linked carbohydrates were altered by removing sialic acids or converting from complex to high mannose or oligomannose glycans, suggesting a regulatory role for carbohydrates in L1-mediated homophilic adhesion. Using the results from tomograms and crystal structures of L1-related molecules, we present a structural model for L1-mediated homophilic adhesion that depends on protein-protein, protein-carbohydrate, and carbohydrate-carbohydrate interactions.


'Exponential peeling' of ventilatory transients following inhalation of 5, 6 and 7% CO2.
The 'exponential peeling' technique has been applied to minute ventilation and tidal volume transients occurring after the abrupt removal of 7, 6 and 5% CO2 in inspired air. These transients, in many cases, were found to be composed of three exponential components, each contributing to the total ventilatory response and each having individual time responses. Gelfand and Lambertsen (1973) have attributed these components to the peripheral chemoreceptors as a group and to two central chemoreceptors. Statistical analysis to determine the constancy of the contribution of the three components over the range of CO2 values studied showed that, although the values for each at the different stimulus levels were not significantly different, the great subject-to-subject variation in the data precluded a firm conclusion about the constancy of the components. Because of a number of considerations it was concluded that exponential peeling of respiratory transients following abrupt removal of CO2 inhalation is not a satisfactory way to approach the problem of the numbers, relative contributions and time responses of the various receptor groups comprising the respiratory controller.


Quantitative characterization of drying-induced cracks and permeability of granite residual soil using micron-sized X-ray computed tomography.
Drying-induced cracks negatively impacts the performance of soils in the context of global warming. Traditional testing approaches used for the cracking characterization of soils are mainly based on surface observation and qualitative inspections. In this study, a temporal investigation of micron-sized X-ray computed tomography (Micro-CT) tests was performed on the granite residual soil (GRS) during desiccation for the first time. Through three-dimensional (3D) reconstructions and seepage simulations, the dynamic evolution of drying-induced cracks and permeability that evolved (0 to 120 h) was visually characterized and intensively quantified. Experimental results show that the averaged area-porosity ratio varies as an increasing trend, appearing fast at first and slowly thereafter during desiccation.. Observed by 3D reconstruction models, connected cracks rapidly propagated through the samples while isolated cracks occupied small volumes and remained almost unchanged. The pore-diameter distribution of GRS reveals that the propagation of connected cracks is essential in influencing soil cracking. The simulated permeability is generally comparable with measuring ones with an acceptable error margin, demonstrating the accuracy of seepage models. The increasing permeability from both experiments and numerical simulations indicates the desiccation process severely impacts the hydraulic properties of soils. This study provides an adamant evidence that the Micro-CT is an effective and feasible tool for the elucidation of drying-induced crack evolutions and in building numerical models for permeability validation.


An international survey on hybrid imaging: do technology advances preempt our training and education efforts?
Hybrid PET/CT and PET/MRI are increasingly important technologies in the evaluation of malignancy and require cooperation between radiologists and specialists in molecular imaging. The aim of our study was to probe the mindsets of radiological and nuclear medicine professionals in regard to current hybrid imaging practice and to assess relevant training aspirations and perceived shortfalls, particularly amongst young professionals. In this context, we initiated an international survey on "Hybrid Imaging Training". An online survey was prepared on-line and launched on October-2, 2016. It was composed of 17 multiple-choice and open questions regarding the professional background, a perspective on hybrid imaging training efforts and lessons to be learned from disparate craft groups. The survey ran for 2 weeks. We report total responses per category and individual free-text responses. In total, 248 responses were collected with a mean age of all responders of (41 ± 11) y. Overall, 36% were within the target age range of (20-35) y. Across all responders, the majority (72%) commented on there being too few hybrid imaging experts in their country, whereas only 1% said that there were too many. Three quarters of the responders were in favour of a curriculum allowing sub-specialisation in hybrid imaging. With respect to reporting of hybrid imaging, confidence increased with age. The average rating across all responders on the level of cooperation among the two specialties suggested a low overall level of satisfaction. However, the survey feedback indicated the local (on-site) cooperation being somewhat better than the perceived cooperation between the relevant associations on a European level. We consider these results to represent an appropriate cross-section of professional opinions of imaging experts across different demographic and hierarchical levels. Collectively they provide evidence supporting a need to address current shortfalls in developing hybrid imaging expertise through national educational plans, and, thus, contribute to helping improve patient care.


Emerging Translational Research in Neurological and Psychiatric Diseases: From In Vitro to In Vivo Models.
Revealing the underlying pathomechanisms of neurological and psychiatric disorders, searching for new biomarkers, and developing novel therapeutics all require translational research [...].


Large-Scale Cultivation of Euglena.
From the middle of the twentieth century, microalgae have been exploited as a candidate biomass source of food and other products. One such candidate source is the fast-proliferating microalga Euglena gracilis. The commercial cultivation of E. gracilis began in 2007, after the success of its outdoor mass cultivation and improvement of the harvesting and drying methods suitable for Euglena cells. The commercialization of Euglena production is based on the strategy of "5Fs of Biomass," which refers to the development and production of commercial products including food, fiber, feed, fertilizer, and fuel from biomass." Although room for improvement remains in the productivity of Euglena biomass, the product with the highest value-food-is already profitable. By enhancing the productivity of its biomass, other Euglena products, including fiber, feed, fertilizer, and fuel, can be commercialized. Breeding and recombinant DNA technology studies are being conducted to accomplish more extensive application of Euglena. In addition, the search for a better place for outdoor mass cultivation of Euglena is ongoing.


Transfer of European Union priority polycyclic aromatic hydrocarbons to lycopene extracted from tomato peel powder and assessment of the risks posed.
Tomato peel is a promising source of lycopene. Benzo(a)pyrene, benzo(a)anthracene, benzo(b)fluoranthene, and chrysene (PAH 4) are polycyclic aromatic hydrocarbons (PAHs) classed as priority pollutants by the European Union that can be sorbed by tomato peel and transferred to lycopene products. Here, the transfer of PAH 4 to extracted lycopene was assessed. Between 77.69% and 102.99% of PAH 4 in tomato peel was transferred to tomato oleoresin. The PAH transfer rate was closely related to the log (octanol-water partition coefficient). PAH partitioning depended on the PAH solubility in the different phases used. Only 0.028%-0.058% of the PAHs entered lycopene crystals, the rest remaining in the residue. This indicated that crystallization efficiently excluded PAH 4. Lycopene crystals 96.71% pure were produced that could be used in various commercial products. An exposure and risk assessment indicated that PAH 4 in lycopene do not pose strong risks to people consuming lycopene microcapsules.


Effects of clonidine and yohimbine on the pupillary light reflex and carbachol-evoked sweating in healthy volunteers.
The effects of single doses of clonidine hydrochloride (200 micrograms), yohimbine hydrochloride (22 mg), a combination of the two treatments, and placebo, on some autonomic functions were studied in healthy volunteers using a double-blind crossover design. Clonidine prolonged the recovery time of the light reflex, lowered systolic blood pressure and reduced subjectively rated alertness; these effects were reversed by yohimbine. Responsiveness of sweat glands to carbachol was not affected by the treatments.


5-HT1A and 5-HT2 receptors mediate hypo- and hyperthermic effects of tryptophan in pargyline-pretreated rats.
Mechanisms of tryptophan (a 5-HT precursor)-induced changes in body temperature were investigated in rats pretreated with pargyline, a monoamine oxidase inhibitor (MAO-I). Tryptophan (100 mg/kg, i.p.) did not affect the body temperature in rats, but it produced significant hypothermia followed by marked hyperthermia and higher mortality in the pargyline-pretreated rats. 5-HT depletion with p-chlorophenylalanine (p-CPA, 100 mg/kg/day for 3 days) significantly suppressed not only the body temperature change but also the mortality and 5-HT syndrome following tryptophan plus pargyline administration. Although propranolol (10 mg/kg, i.p.), a beta-adrenoceptor antagonist, did not alter the hypothermia caused by tryptophan in the pargyline-pretreated rats, pindolol (2 mg/kg, S.C.), a 5-HT1A receptor and beta-adrenoceptor antagonist, suppressed the hypothermia but not the hyperthermia or mortality caused by the same treatment. On the other hand, spiperone and ketanserin, 5-HT2 receptor antagonists, at doses of 3 mg/kg, potentiated the hypothermia and completely suppressed the hyperthermia and mortality caused by tryptophan in the pargyline-pretreated rats. These results suggest that tryptophan-induced hypo- and hyperthermia are mediated by 5-HT1A and 5-HT2 receptors, respectively, in the pargyline-pretreated pretreated rats.


AnAnkle Trial study protocol: a randomised trial comparing pain profiles after peripheral nerve block or spinal anaesthesia for ankle fracture surgery.
Ankle fracture surgery is a common procedure, but the influence of anaesthesia choice on postoperative pain and quality of recovery is poorly understood. Some authors suggest a benefit of peripheral nerve block (PNB) in elective procedures, but the different pain profile following acute fracture surgery and the rebound pain on cessation of the PNB both remain unexplored. We present an ongoing randomised study aiming to compare primary PNB anaesthesia with spinal anaesthesia for ankle fracture surgery regarding postoperative pain profiles and quality of recovery. AnAnkle Trial is a randomised, dual-centre, open-label, blinded analysis trial of 150 adult patients undergoing primary internal fixation of an ankle fracture. Main exclusion criteria are habitual opioid use, impaired pain sensation, other painful injuries or cognitive impairment. The intervention is ultrasound-guided popliteal sciatic (20 mL) and saphenal nerve (8 mL) PNB with ropivacaine 7.5 mg/mL, and controls receive spinal anaesthesia (2 mL) with hyperbaric bupivacaine 5 mg/mL. Postoperatively all receive paracetamol, ibuprofen and patient-controlled intravenous morphine on demand. Morphine consumption and pain scores are registered in the first 27 hours and reported as an integrated pain score as the primary endpoint. Pain score intervals are 3 hours and we will use the area under curve to get a longitudinal measure of pain. Secondary outcomes include rebound pain on cessation of anaesthesia, opioid side effects (Opioid-Related Symptom Distress Scale), quality of recovery (Danish Quality of Recovery-15 score) and pain scores and medication days 1-7 (diary). The study has been approved by the Regional Ethics Committees in the Capital Region of Denmark, the Danish Data Protection Agency and the Danish Health and Medical Authority. We will publish the results in international peer-reviewed medical journals. AnAnkle Trial is registered in the European Clinical Trials Database (EudraCT 2015-001108-76).


[Establishment of human multidrug-resistant lung carcinoma cell line (D6/MVP)].
To establish human multidrug-resistant lung carcinoma cell line (D6/MVP) with its characteristics studied. Intermittent administration of high-dose MMC, VDS and DDP (MVP) was used to induce human lung carcinoma cell line (D6) to a multidrug-resistant variety (D6/MVP). MTT assay was used to study the multidrug resistance of D6/MVP to multianticarcinogen. Flow cytometry was used to study the cell cycle distribution and the expression of P-gp, multidrug resistance-associated protein (MRP) and GSH/GST. 1. D6/MVP was resistant to many anti-tumor agents, with the IC(50) 13.3 times higher and the drug resistance 2 - 6 times higher than D6, 2. The multiplication time of D6/MVP was prolonged and the cell number of S-phase decreased while that of G1- and G(2)-phase increased and 3. The expression of P-gp and MRP was enhanced significantly (96.2% vs 51.7%), but the expression of GSH/GST kept stable. D6/MVP is a multidrug-resistant cell line possessing the basic characteristics of drug-resistance.


Application of validated method for determination of selected polychlorinated biphenyls in human adipose tissue samples.
The validation method has been employed to determine PCBs in human female adipose tissue and in different tissue samples (brain, kidney, liver and adipose tissue) collected from five donors from the Wielkopolska region, Poland. The contents of 15 PCB congeners have been determined in the tissues (brain, kidney, liver and adipose tissue) of 5 donors aged 18-78. The highest PCB concentrations have been found in the adipose tissue, in which the total of 15 congeners occur in the amount 78-591ng/g tissue, and in the liver tissue in the amount 16-94ng/g tissue. In 16 samples of adipose tissue taken from women aged 25-36, 4 PCB congeners (PCB 105, 138, 150 and 180) have been determined. The mean content of the total of these congeners has been 41ng/g tissue. This result is lower than the concentration of analogous PCB in the tissues collected from women from the other European countries, which well correlates with the low content of PCB in the food produced in Poland.


Initial bridges between two ribosomal subunits are formed within 9.4 milliseconds, as studied by time-resolved cryo-EM.
Association of the two ribosomal subunits during the process of translation initiation is a crucial step of protein synthesis. The two subunits (30S and 50S) of the bacterial 70S ribosome are held together by 12 dynamic bridges involving RNA-RNA, RNA-protein, and protein-protein interactions. The process of bridge formation, such as whether all these bridges are formed simultaneously or in a sequential order, is poorly understood. To understand such processes, we have developed and implemented a class of microfluidic devices that mix two components to completion within 0.4 ms and spray the mixture in the form of microdroplets onto an electron microscopy grid, yielding a minimum reaction time of 9.4 ms before cryofixation. Using these devices, we have obtained cryo-EM data corresponding to reaction times of 9.4 and 43 ms and have determined 3D structures of ribosomal subunit association intermediates. Molecular analyses of the cryo-EM maps reveal that eight intersubunit bridges (bridges B1a, B1b, B2a, B2b, B3, B7a, B7b, and B8) form within 9.4 ms, whereas the remaining four bridges (bridges B2c, B4, B5, and B6) take longer than 43 ms to form, suggesting that bridges are formed in a stepwise fashion. Our approach can be used to characterize sequences of various dynamic functional events on complex macromolecular assemblies such as ribosomes.


Advantageous use of SFC for separation of crude therapeutic peptides and peptide libraries.
A simple SFC/MS (Supercritical Fluid Chromatography/Mass Spectrometry) method set was developed to effectively screen separations of various crude synthetic peptide products of pharmaceutical interest. Additives to the modifier methanol which were successful for these separations were found to include TFA (trifluoroacetic acid) and ammonia mixed with TFA, each at 0.1 % (v/v) composition in methanol. A final screening column set consisted of 2-ethylpyride (2-EP), 4-ethylpyridine (4-EP) and cross-linked diol (Luna™ HILIC) stationary phases. Small, linear and macrocyclic peptides with fewer than ten residues could all be eluted with good performance under at least one of the method conditions comprising the final screening protocol. For larger peptides either the 4-EP and HILIC columns with the above additives provided a good initial screening method set without 2-EP. The gradient was slightly longer and shifted to higher polarity relative to the gradients for smaller peptides. This method was often successful to elute large, hydrophilic peptides up to a 41-mer with acceptable peak profiles although the largest peptides with most ionizable residues were most challenging. For these peptides generally HILIC column performance was better with TFA + ammonia in the modifier than with TFA, while 4-EP performance was usually improved with TFA relative to TFA + ammonia.


Left Atrial Strain Identifies Increased Atrial Ectopy in Patients with Beta-Thalassemia Major.
Patients with beta-thalassemia major (β-ΤΜ) may develop cardiac arrhythmias through a multifactorial mechanism. The current study evaluated the association of cardiac structure and function on echocardiography with atrial ectopic burden on 24-hour tape recording in β-ΤΜ patients. This prospective study included consecutive β-ΤΜ patients. Demographic, laboratory, echocardiographic, cardiac magnetic resonance (CMR) T2* and 24-hour tape recording data were prospectively collected. The patients were classified according to the median value of premature atrial contractions (PACs) on 24-hour tape. In total, 50 β-TM patients (37.6 ± 9.1 years old, 50% male) were divided in 2 groups; PACs ≤ 24/day and > 24/day. Patients with PACs > 24/day were treated with blood transfusion for a longer period of time (39.0 ± 8.6 vs. 32.0 ± 8.9 years, p < 0.007), compared to their counterparts. Older age (OR: 1.121, 95% CI: 1.032-1.217, p = 0.007), longer duration of blood transfusion (OR:1.101, 95% CI:1.019-1.188, p = 0.014), larger LV end-diastolic diameter (OR: 4.522, 95% CI:1.009-20.280, p = 0.049), higher values of LA peak systolic strain (OR: 0.869, 95% CI: 0.783-0.964, p = 0.008), higher MV E/E' average (OR: 1.407, 95% CI: 1.028-1.926, p = 0.033) and higher right ventricular systolic pressure (OR: 1.147, 95% CI: 1.039-1.266, p = 0.006) were univariably associated with PACs > 24/day. LA peak systolic strain remained significantly associated with PACs > 24/day after adjusting for the duration of blood transfusions or for CMR T2*. The multivariable model including blood transfusion duration and LA peak systolic strain was the most closely associated with PACs > 24/day. Receiver operating characteristic curve analysis identified a left atrial peak systolic strain of 31.5%, as the best cut-off value (83% sensitivity, 68% specificity) for prediction of PACs > 24/day. In β-TM patients, LA peak systolic strain was associated with the atrial arrhythmia burden independently to the duration of blood transfusions and CMR T2*.


Graft Infection Masquerading as Rheumatologic Disease: a Rare Case of Aortobifemoral Graft Infection Presenting as Hypertrophic Osteoarthropathy.
Prosthetic vascular graft procedures are a common treatment modality for peripheral vascular disease. A relatively common complication is graft infection, occurring at a rate of 0.5-5%. When they occur, graft infections are associated with significant morbidity and mortality. Vascular graft infections also represent a diagnostic and therapeutic challenge for the physician METHODS: Here, we report a case where the rare finding of secondary hypertrophic osteoarthropathy was an important indication of underlying aortic graft infection that was initially misdiagnosed. A review of the literature revealed 34 cases of vascular graft infection associated with hypertrophic osteoarthropathy. The mean interval from surgery to time of infection was approximately 5 years. Mortality was 35%. When combined with hypertrophic osteoarthropathy, vascular graft infection was complicated by an aortoenteric fistula in 53% of the cases. The complexity of this case highlights the challenges physicians face in order to diagnose and treat this condition.


R&D efficiency of leading pharmaceutical companies - A 20-year analysis.
Comparative analysis of the R&D efficiency of 14 leading pharmaceutical companies for the years 1999-2018 shows that there is a close positive correlation between R&D spending and the two investigated R&D output parameters, approved NMEs and the cumulative impact factor of their publications. In other words, higher R&D investments (input) were associated with higher R&D output. Second, our analyses indicate that there are 'economies of scale' (size) in pharmaceutical R&D.


Right Atrial Complexity Evolves With Stepwise Left-Sided Persistent Atrial Fibrillation Substrate Ablation and Predicts Outcomes.
This study sought to study the relation between outcomes of modified stepwise atrial fibrillation (AF) substrate ablation and dynamic electrogram characteristics in the coronary sinus (CS) and right atrium (RA). Identifying patients with persistent AF who will benefit from limited lesion sets versus those requiring extensive substrate modification is challenging. We studied 70 patients undergoing persistent AF ablation, 43 with acute success (successful ablation [sABL], AF termination, or noninducibility) and 27 with failure (failed ablation [fABL], no termination, or induced AF of >5 minutes). Dominant frequency (DF) and sample entropy (SampEn, increasing with signal complexity) were measured on 30-second recordings of wide-coverage simultaneous RA and CS electrograms during baseline AF and induced AF post-pulmonary vein isolation and after left-sided electrogram-guided ablation steps (on the CS with or without the left atrium [LA]). At baseline AF, patients with sABL exhibited lower RA SampEn (p = 0.023) and lower CS DF (p = 0.030) compared to fABL. A positive RA-to-CS SampEn gradient predicted ablation failure (48% vs. 19% for patients in fABL vs. sABL; p = 0.015). A positive RA-to-CS DF gradient developed in patients with fABL after extra-pulmonary vein substrate modification, unlike patients with sABL (p = 0.0008). At 24 months, 76% of patients were AF free, and 68% were arrhythmia free. sABL was associated with fewer AF recurrences (hazard ratio: 0.31; 95% confidence interval: 0.12-0.84; p = 0.021). A negative RA-to-CS SampEn gradient at baseline was associated with freedom from AF (-0.14 ± 0.19 vs. 0.04 ± 0.18; p = 0.002). RA greater than CS electrogram complexity gradients at baseline or developing during ablation are associated with unfavorable acute and long-term outcomes of persistent AF ablation. These parameters allow monitoring of the effects of left-sided substrate ablation and, therefore, a rational choice of additional RA substrate modification.


Human L-DOPA decarboxylase mRNA is a target of miR-145: A prediction to validation workflow.
l-DOPA decarboxylase (DDC) is a multiply-regulated gene which encodes the enzyme that catalyzes the biosynthesis of dopamine in humans. MicroRNAs comprise a novel class of endogenously transcribed small RNAs that can post-transcriptionally regulate the expression of various genes. Given that the mechanism of microRNA target recognition remains elusive, several genes, including DDC, have not yet been identified as microRNA targets. Nevertheless, a number of specifically designed bioinformatic algorithms provide candidate miRNAs for almost every gene, but still their results exhibit moderate accuracy and should be experimentally validated. Motivated by the above, we herein sought to discover a microRNA that regulates DDC expression. By using the current algorithms according to bibliographic recommendations we found that miR-145 could be predicted with high specificity as a candidate regulatory microRNA for DDC expression. Thus, a validation experiment followed by firstly transfecting an appropriate cell culture system with a synthetic miR-145 sequence and sequentially assessing the mRNA and protein levels of DDC via real-time PCR and Western blotting, respectively. Our analysis revealed that miR-145 had no significant impact on protein levels of DDC but managed to dramatically downregulate its mRNA expression. Overall, the experimental and bioinformatic analysis conducted herein indicate that miR-145 has the ability to regulate DDC mRNA expression and potentially this occurs by recognizing its mRNA as a target.


Relationships between soil pollution by heavy metals and melanin-dependent coloration of a fossorial amphisbaenian reptile.
Melanin is the basis of coloration in many animals, and although it is often used in communication, thermoregulation, or camouflage, melanin has many other physiological functions. For example, in polluted habitats, melanin can have a detoxifying function. Melanic coloration would help to sequester in the skin the heavy metal contaminants from inside the body, which will be expelled to the exterior when the skin is sloughed. Moreover, animals should have evolved more melanic colorations in more polluted habitats ("industrial melanism" hypothesis). We examined whether the fossorial amphisbaenian reptile, Trogonophis wiegmanni, is able to eliminate heavy metals, derived from soil pollution by seagull depositions, through sloughing its skin. Our results suggest a covariation between levels of soil pollution by heavy metals and the concentration of heavy metals in the sloughed skins of amphisbaenians. This suggests that amphisbaenians may expel heavy metals from their bodies when they slough the skins. We also tested whether amphisbaenians inhabiting soils with higher levels of heavy metal pollution had darker (melanin-dependent) body colorations. However, contrary to predictions from the "industrial melanization" hypothesis, we found a negative relationship between soil pollution and proportions of melanic coloration. This contradictory result could, however, be explained because heavy metals have endocrine disruption effects that increase physiological stress, and higher stress levels could result in decreased melanogenesis. We suggest that although amphisbaenians might have some detoxifying mechanism linked to melanin in the skin, this process might be negatively affected by stress and result ineffective under conditions of high soil pollution.


Scoliosis and dental occlusion: a review of the literature.
Idiopathic scoliosis is a deformity without clear etiology. It is unclear wether there is an association between malocclusion and scoliosis. Several types of occlusion were described in subjects with scoliosis, mostly case-reports. The aim of this review was to evaluate the type of occluslins more prevalent in subjects with scoliosis All randomised and controlled clinical trials identified from the Cochrane Oral Health Group Trials Register, a MEDLINE search using the Mesh term scoliosis, malocclusion, and relevant free text words, and the bibliographies of papers and review articles which reported the outcome of orthodontic treatment in subjects with scoliosis that were published as abstracts or papers between 1970 and 2010. All randomised and controlled clinical trials published as full papers or abstracts which reported quantitative data on the outcomes malocclusion in subjects with scoliosis. Data were extracted without blinding to the authors, age of patients or type of occlusion. Using the search strategy eleven observational longitudinal studies were identified. No randomized clinical trials were recorded. Twenty-three cross-sectional studies were recorderd, and the others studies were reviews, editorials, case-reports, or opinions. The clinical trials were often not controlled and were about the cephalometric evaluation after treatment with the modified Milwuakee brace, followed by the orthodontic treatment of the class II relationship with a functional appliance. Clinical trials also included the study of the associations between scoliosis and unilateral crossbite, in children with asymmetry of the upper cervical spine. This association was also investigated in rats, pigs and rabbits in clinical trials. The other associations between scoliosis and occlusion seems to be based only on cross-sectional studies, case-reports, opinions. Based on selected studies, this review concludes that there is plausible evidence for an increased prevalence of unilateral Angle Class II malocclusions associated with scoliosis, and an increased risk of lateral crossbite, midline deviation in children affected by scoliosis. Also, documentation of associations between reduced range of lateral movements and scoliosis seem convincing. Data are also mentioned about the association between plagiocephaly and scoliosis.


Same-Sex Behavior and its Relationship with Sexual and Health-Related Practices Among a Population-Based Sample of Women in Puerto Rico: Implications for Cancer Prevention and Control.
This secondary data analysis aimed to estimate the prevalence of same-sex behavior and sexual and health-related practices of a population-based sample (n=560) of women aged 16-64 years in Puerto Rico (PR). Data collection included interviews and biologic samples. Seven percent of the sample had had sex with other women (WSW). Age-adjusted logistic regression models indicated that WSW had higher odds of history of cancer, having ≥ 7 lifetime sexual partners, using sex toys and sharing them, and use of tobacco and illicit drugs. Future research is needed to address the health needs of WSW, including cancer-related risk factors and sexual practices.


The teflon sling operation for repair of complete rectal prolapse.
Sixty-four cases of complete rectal prolapse have been treated by the Teflon sling operation since 1969. One case has recurred. No sepsis has occurred. Approximately 80% of patients followed are totally continent. This relatively simple operation seems to be the procedure of choice in this disease.


"Identifying Pleasure: a Diary-Approach to the Embodied Subjectivity of Students' Daily Life in Albania".
The present study examines the embodied feelings of daily-life among a sample of Albanian college students. The specific methodology of 'body-diaries' used for such a purpose goes beyond a mere experimental writing, it fosters a creative and (un)comfortable way for making sense of bodies as subjects. Sharing intimacy and co-constructing pleasure and pain takes place in the unpopular, pre-web 2.0, textual format of a diary, lacking of the contemporary usual online audience. The innovative aspect, here, is the explicit focus on putting one's body into words in daily-life. Such a methodology stems from embodiment and critical sexuality studies and follows the idea that symbolic realms and abstraction are always already materially located and speaking. The complex relationships between language and body is elaborated with respect to systemic and individual communication strategies. How do we come to terms with sensations of pleasure in our everyday routine? How do students approach themselves and others when explicitly asked to focus on bodily issues in a rapidly changing society like Albania? A a particular emphasis will be given, then, to the ongoing transformations between public and private spheres and related affective reconfigurations.


Causes of Emotional Eating and Matched Treatment of Obesity.
Eating in response to negative emotions (EE) may be an explanatory factor of the weight regain of many dieters. This narrative review presents evidence on possible causes of EE and the association of EE with depression and obesity and discusses implications of these findings for the treatment of obesity. Possible causes of EE are high dietary restraint, poor interoceptive awareness, alexithymia, emotion dysregulation and a reversed hypothalamic pituitary adrenal (HPA) stress axis. EE may be the outcome of inadequate parenting or depressive feelings in interaction with genetic susceptibility. There is also robust evidence that EE is a mediator between depression and obesity. The association of EE with depression and poor emotion regulation skills suggests that the treatment of obese people with high EE should not focus on calorie-restricted diets but on emotion regulation skills. The DEBQ (Dutch Eating Behavior Questionnaire) enables such a matched treatment of obesity.


Lipidated gemini peptide amphiphiles with enhanced loading capacity and cell membrane affinity for drug delivery.
Lipidated peptide amphiphiles exhibit high affinity for plasma cell membranes, good cell internalization and improved stability against degradation, which make them attractive as a drug delivery system. However, low drug loading capacity limits their application for drug delivery. Herein, we developed a gemini peptide amphiphile with enhanced membrane activity and endosomal escape, containing dodecanoic acid hydrophobic tails at the N-terminus, rhodamine on the pendant chain and an active targeting peptide sequence (GRGDS). The presence of rhodamine not only provides high drug loading capability due to the π-π stacking interaction between camptothecin (CPT) and rhodamine, but also promotes peptide amphiphiles to form compact spherical micelles, as well as allows for fluorescence imaging. Single-molecule total internal reflection fluorescence microscopy investigation reveals gemini peptide amphiphile has higher affinity for plasma cell membranes than single-tail peptide amphiphile. Meanwhile, better cell internalization of gemini peptide amphiphile was confirmed by flow cytometry and confocal laser scanning microscopy. Moreover, CPT-loaded gemini peptide amphiphile induced enhanced cytotoxicity in cancer cells when compared to free CPT, indicating that lipidated peptide amphiphile with π-conjugates on the pendant chain and two hydrophobic tails can serve as a highly efficient drug delivery vehicle.


Presumed vitelliform dystrophy with perimacular flecks and retinal detachment.
Seven of eight siblings of asymptomatic non-consanguineous parents were investigated. Two of them had atrophic cystoid macular degeneration and flat or subnormal electro-oculograms suggesting the diagnosis of vitelliform dystrophy. In one eye the central cystoid lesion was surrounded by atypical small whitish hyperfluorescent flecks resembling fundus flavimaculatus. In the other eye of this patient cystoid macular degeneration progressed to shallow non-rhegmatogenous detachment of the retina. One of the asymptopmatic siblings had a mild colour vision defect of tritan-type and some fleckish hyperfluorescence around the macula and another sister showed abnormal EOG responses. These patients are probably carriers of the pathological gene responsible for the disease.


Parallel Aligned Nickel Nanocone Arrays for Multiband Microwave Absorption.
Magnetic nanostructures with conical shape are highly desired for pursuing extraordinary magnetic properties and microwave absorption. However, the fabrication of such nanostructures with controlled shape and size uniformities and alignment is not yet realized. Accordingly, the magnetic properties and their application as microwave absorber are not well understood. Here, we report on the first demonstration of controlled fabrication of soft magnetic nickel nanocone arrays with sharp geometry, large aspect ratio, uniform size, and parallel alignment. The imaginary part of the relative complex permeability shows multiband absorption in the 2-17 GHz range. Such an exceptional microwave absorption results from the uniform conical shape and size and the parallel alignment. The absorption mechanisms are discussed under the framework of natural resonance and exchange resonance. The natural resonance is dependent on the shape anisotropy and facilitated by the conical geometry. The exchange resonance is well explained by the observation of the bulk spin waves with exchange coupling at the tip of nanocones using the inelastic light scattering and is consistent with exchange theory predictions for the quantization of bulk spin waves. We expect that our work will shed light on the physical insights into the magnetic properties of nanocones and find great potential in applications of microwave absorption.


Comparative pharmacokinetic study of PEGylated gemcitabine and gemcitabine in rats by LC-MS/MS coupled with pre-column derivatization and MSALL technique.
Gemcitabine is a small molecular antitumor compound used to treat many types of solid tumors. The clinical application of gemcitabine is limited by its short biological half-life, rapid metabolism and poor tumor tissue targeting. The covalent attachment of polyethylene glycol to gemcitabine is a promising technique to overcome these limitations. After PEGylation, PEGylated gemcitabine could be metabolized into gemcitabine and its metabolites in vivo. Due to the scale effect of PEGylated gemcitabine, the DMPK process of the original drug is greatly changed. Therefore, understanding the pharmacokinetic behavior of PEGylated gemcitabine, gemcitabine and the metabolite dFdU in vivo is really important to clarify the antitumoral activity of these compounds. It would also guide the development of other PEGylated drugs. Due to the complex structure and diverse physiochemical property of PEG, direct quantification analysis of PEGylated gemcitabine presented many challenges in terms of assay sensitivity, selectivity, and robustness. In this article, a data-independent acquisition method, MSALL-based approach using electrospray ionization (ESI) coupled quadrupole time of flight mass spectrometry (MS), was utilized for the determination of PEGylated gemcitabine in rat plasma. The technique consists of a Q1 mass window through all the precursor ions, fragmenting and recording all product ions. PEGylated gemcitabine underwent dissociation in collision cell to generate a series of PEG related ions at m/z 89.0604, 133.0868, 177.1129 of 2, 3, 4 repeating ethylene oxide subunits and PEGylated gemcitabine related ions at m/z 112.0514. PEGylated gemcitabine was detected by the high resolution extracted ions based on the specific compound. For gemcitabine and dFdU, the study used derivatization of these high polarity compounds with dansyl chloride to improve their chromatographic retention. This paper describes comparative pharmacokinetic study of PEGylated gemcitabine and gemcitabine in rats by LC-MS/MS coupled with pre-column derivatization and MSALL technique. The results show that PEGylation could reduce the drug clearance of the conjugated compounds and increase the drug plasma half-life. After administration of PEGylated gemcitabine, the exposure of the free gemcitabine in vivo is lower than administration of gemcitabine, which means that PEGylated gemcitabine possesses lower toxicity compared with gemcitabine.


Signal amplification of novel sandwich-type genosensor via catalytic redox-recycling on platform MWCNTs/Fe3O4@TMU-21 for BRCA1 gene detection.
The MWCNTs/Fe3O4@TMU-21 as a novel electrochemical sandwich-type genosensor was fabricated to detect the BRCA1 gene using the redox-cycling ferrocene functionalized reporter label probe (r-Fc-DNA). In the designed genosensor, the capture probe (cDNA) and r-Fc-DNA were used to detect the BRCA1 gene in sandwich-type genosensor, in which DNA sequences are well -hybridized with the BRCA1 gene (t-DNA). The cDNA was immobilized on the multiwall carbon nanotube and metal-organic framework with Fe3O4 nanoparticle core, which is the sensor platform. Target DNA was assayed by redox-recycling reporter probe (r-Fc-DNA) using the electro-catalytic activity of ferri/ferrocyanide, which results in significantly enhanced the oxidation peak current of r-Fc-DNA. The electrochemical redox cycling led to a high signal-to-noise ratio for gene assay. MWCNTs and Fe3O4@TMU-21 were applied to increase the platform conductivity and suitable binding of the recognition elements. This constructed genosensor plays an influential role in increasing the sensitivity of BRCA1 gene sequence recognition. So that under optimal conditions, this genosensor illustrated a wide linear range from 1.0×10-15 to 1.0×10-10 M with a detection limit of 0.57 × 10-15 M. Moreover, the genosensor exhibited high selectivity, stability, and reproducibility. The obtained recoveries (between 91 and 105%) of the BRCA1 gene assay in human blood samples satisfactory, which can be used for BRCA1 gene measurement in the laboratory.


Apoptosis of N-type neuroblastoma cells after differentiation with 9-cis-retinoic acid and subsequent washout.
The overall survival rate for patients with neuroblastoma has improved over the past two decades, but long-term survival for the subgroup of patients with high-risk disease remains low. In recent years, there has been interest in the potential clinical use of drugs able to induce differentiation of neuroblastoma cells. Since 9-cis-retinoic acid induces better and more sustained differentiation of neuroblastoma in vitro than other retinoic acid isomers, this may be a more appropriate retinoid for use in neuroblastoma therapy. The purpose of this work was to compare the long-term effects of all-trans- and 9-cis-retinoic acid on neuroblastoma differentiation using an N-type (neuroblastic) cell line, SH SY 5Y, as an in vitro model. In addition, we wanted to find out whether 9-cis-retinoic acid would induce programmed cell death (apoptosis) in these N-type neuroblastoma cells and to determine whether the effects of either 9-cis- or all-trans-retinoic acid are dependent on their continued presence in the culture medium. SH SY 5Y cells were incubated in either the continued presence of all-trans- or 9-cis-retinoic acid or for 5 days with retinoic acid followed by culture in the absence of retinoid for up to 13 days. Morphologic changes were observed using phase-contrast and scanning electron microscopy. Apoptosis was determined by flow cytometry of propidium iodide-stained cells and by using terminal deoxynucleotidyl transferase to end-label DNA fragments in situ in apoptotic cells. Culture of SH SY 5Y cells with all-trans- or 9-cis retinoic acid for 5 days induced morphologic differentiation and inhibited cell growth. These effects were maintained in the continuous presence of each retinoic acid isomer but were more profound in cells treated with 9-cis-retinoic acid. The differentiation of cells treated with all-trans-retinoic acid was reversible once retinoic acid was removed from the medium. Conversely, apoptosis was induced in cells treated with 9-cis-retinoic acid for 5 days and cultured for 9 days (4 days after washout) but not in cells cultured in the continuous presence of 9-cis-retinoic acid. This effect was specific to 9-cis-retinoic acid. Previous studies have demonstrated differential responses to all-trans-retinoic acid in N- and S-type (substrate-adherent or Schwann-like) neuroblastoma cells: Apoptosis is induced in S-type cells, whereas differentiation occurs in N-type cells. The present results show that, unlike all-trans-retinoic acid, 9-cis-retinoic acid induces both differentiation and apoptosis in N-type SH SY 5Y neuroblastoma cells. However, apoptosis was dependent on removal of 9-cis-retinoic acid from the culture medium. Since both differentiation and apoptosis are involved in tumor regression, 9-cis-retinoic acid may be a more appropriate retinoid for clinical trials in neuroblastoma. The dependence of apoptosis on treatment and subsequent removal of 9-cis-retinoic acid implies that drug scheduling may be an important parameter affecting therapeutic efficacy.


Radiobrominated spiroperidol for the study of dopamine D2 receptors.
Some neuropsychiatric disorders have been suggested to be related to the CNS dopaminergic system. In order to probe this neurotransmitter system, radiobrominated spiroperidol, a potent dopamine (DA) D2-receptor antagonist, was developed. This review deals with the routine synthesis of [75, 76, or 77Br]-p-bromospiroperidol (BrSP), its validation as a radiopharmaceutical directed to DA D2 receptors, and the imaging studies which have been done using this radioligand with either single photon tomography (SPECT) or positron tomography (PET). [*Br]BrSP will be compared to other D2 ligands currently available. The present state and future direction of DA receptor research, in particular, the quantitative aspects, will be discussed.


Gyejibokryeong-Hwan improves recovery of injured muscles in mouse model of muscle contusion.
To investigate the effects of Gyejibokryeong-Hwan (Guizhifuling-wan, GBH) on muscle injury in a mouse model of muscle contusion. C57/BL6 mouse biceps femoris muscles were injured using the drop-mass method and injured animals were treated orally with GBH (50, 100, or 500 mg/kg) once a day for 7 d. Open field and treadmill running tests were performed to assess functional recovery from muscle injury. The production of pro-inflammatory cytokines was examined by enzyme-linked immunosorbent assay and Western blotting analysis. Expression of the muscle regeneration biomarkers, myoblast determination (MyoD), myogenic factor 5 (Myf5), and smooth muscle actin (α-SMA), in the biceps femoris muscle was investigated at the protein and mRNA level by Western blotting and real time-PCR, respectively. Histological analysis was performed using hematoxylin and eosin staining. Finally, myosin heavy chain production was investigated in differentiated C2C12 myoblasts in the presence of GBH. GBH treatment markedly improved locomotion and running behavior. GBH significantly inhibited the secretion of monocyte chemoattractant protein-1 into the bloodstream in muscle-contused animals. The levels of MyoD, Myf5, and α-SMA protein and mRNA were significantly up-regulated by GBH in injured muscle tissue. Histological studies suggested that GBH facilitated recovery from muscle damage. However, GBH did not induce the production of myosin heavy chain in vitro. Overall, the present study suggested that GBH improves the recovery of the injured muscles in the mouse model of muscle contusion.


Convergent Validity of Myheartsmap: A Pediatric Psychosocial Health Screening Tool.
Recognition of pediatric mental health concerns often depends on assessment by parents, educators, and primary care professionals. Therefore, a psychosocial screening instrument suitable for routine use in schools and primary care is needed. The Pediatric Quality of Life (PedsQL) and the Strengths and Difficulties Questionnaire (SDQ) are widely used for screening but lack adolescent-specific mental health measures. MyHEARTSMAP is an instrument assessing aspects of youth psychosocial health via four domains: Psychiatry, Function, Social, and Youth Health. We evaluated MyHEARTSMAP convergent validity with PedsQL and SDQ among 122 child-parent dyads participating in a larger concussion study. Convergent validity was assessed via correlations: MyHEARTSMAP Psychiatry and Function domains correlated strongly (r ≥ 0.44) and Social domain correlated weakly (r ≤ 0.25) to corresponding PedsQL and SDQ subscales, while Youth Health domain correlated moderately (r ≥ 0.31) to the tools' total scales. In conclusion, MyHEARTSMAP converges with PedsQL and SDQ, and benefits from the inclusion of adolescent-specific psychosocial measures.