Dyneon THV, a fluorinated thermoplastic as a novel material for microchip capillary electrophoresis.
In this work, we have investigated Dyneon THV, a fluorinated material, as a new material to afford electrokinetic separations in microfluidic devices. To overcome protein adsorption, two poly(ethylene oxide) (PEO)-based coatings have been investigated: Pluronic F127 and PEO stearate 40. The best results were obtained with the PEO stearate 40 coating which allowed decreasing the surface contact angle from 91 ± 3 to 76°± 3. With this surface treatment, a 66% reduction of the electroosmotic mobility at pH 8.0 and a marked suppression of protein adsorption were observed compared to a native Dyneon THV microchip. Finally, a separation of fluorescently labeled proteins (bovine serum albumin and trypsin inhibitor), well-known for their strong tendency to adsorb on hydrophobic surfaces, was successfully achieved in an HEPES buffer with a PEO stearate 40 treated microchip by capillary zone electrophoresis. Furthermore, we demonstrated the possibility to perform non-aqueous capillary electrophoresis analysis of hydrophobic dyes using various solvents in untreated microchips. The overall results demonstrated not only the suitability of the Dyneon THV microchip for electrokinetic separations, but also its versatility allowing different separation modes to be implemented with the same microchip material.


Involvement of spindles in memory consolidation is slow wave sleep-specific.
Both sleep spindles and slow oscillations have been implicated in sleep-dependent memory consolidation. Whereas spindles occur during both light and deep sleep, slow oscillations are restricted to deep sleep, raising the possibility of greater consolidation-related spindle involvement during deep sleep. We assessed declarative memory retention over an interval containing a nap and determined spindle density for light and deep sleep separately. In deep sleep, spindle density was considerably higher and showed a strong and robust positive correlation with retention. This relation was absent for light sleep, suggesting that the potentiating effects of spindles are tied to their co-occurrence with slow oscillations.


Inhibition of luteinizing hormone, follicle-stimulating hormone and sex-steroid levels in men and women with a potent antagonist analog of luteinizing hormone-releasing hormone, Cetrorelix (SB-75).
Cetrorelix (SB-75; [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10] luteinizing hormone-releasing hormone (LHRH)) is a new highly potent antagonist analog of LHRH containing the D-ureidoalkyl amino acid D-citrulline at position 6 and is free of allergenic effects. This study shows the inhibition of LH and follicle-stimulating hormone (FSH) release in normal men, postmenopausal women and patients with gonadal dysgenesis, using different doses and i.m., s.c. and i.v. routes of administration of SB-75. The mean serum levels of LH and FSH in normal men who received one single dose of 300 micrograms of SB-75 sc started to decline rapidly 1 h after its administration; the LH suppression was sustained for 14 h and that of FSH up to 24 h or longer as the samples were obtained only up to this time. The nadir for LH was reached at 14 h and that for FSH at 24 h or later after administration of the antagonist (p < 0.05). Serum levels of total and free testosterone decreased after the first hour and this inhibition was maintained for up to 14 h. The nadir for total testosterone was at 6 h and that for free testosterone was at 8 h (p < 0.001), corresponding to 56% and 60% of inhibition, respectively. In postmenopausal women, inhibition of the elevated basal serum LH and FSH levels occurred after a single injection of the antagonist analog SB-75 in doses of 75, 150, 300, 600 and 1200 micrograms using im, sc and iv routes of administration.(ABSTRACT TRUNCATED AT 250 WORDS)


Synthesis, characterization, and x-ray crystal structures of cyclam derivatives. 8. Thermodynamic and kinetic appraisal of lead(II) chelation by octadentate carbamoyl-armed macrocycles.
En route toward the development of hybrid organic-inorganic extracting materials incorporating lead-selective chelators and their implementation in water purification processes, the lead(II) binding properties of three N-carbamoylmethyl-substituted 1,4,8,11-tetraazacyclotetradecanes (cyclams) have been fully investigated by spectroscopic (IR, UV-vis, MALDI-TOF MS, (1)H and (13)C NMR), X-ray crystallographic, potentiometric, and kinetic methods. Solution NMR studies revealed that the Pb(2+) ion is entrapped in a molecular cage constituted by the four macrocyclic nitrogen and four amidic oxygen atoms. Protonation and lead binding constants determined in aqueous solution were shown to be linearly dependent, so that all three derivatives possess a similar affinity at any pH value. Thermodynamic and kinetic parameters revealed the crucial role played by the intramolecular hydrogen bonds also evidenced in the crystal structure of the tetraacetamide derivative L(1), which involve the lone pair of each macrocyclic tertiary amine and one amidic hydrogen atom belonging to the appended arm. In contrast to L(1), the absence of such intramolecular interactions for N-(dimethyl)carbamoylmethyl- and N-(diethyl)carbamoylmethyl-substituted cyclams (L(2) and L(3), respectively) accounts for the 2-3 orders of magnitude enhancement of their proton and lead binding affinities. Stopped-flow kinetic measurements enabled unraveling the formation process of the three lead(II) complexes that proceeds in a single rate-limiting step according to the Eigen-Winkler mechanism, while the apparent rate constants were found to increase in the order L(3) < L(2) << L(1) as a consequence of the more acidic character of L(1). A common proton-assisted dissociation mechanism has been found for the three lead(II) complexes, which involves the rapid formation of a protonated, six-coordinate intermediate followed by either a unimolecular decomposition or a bimolecular attack of a second hydronium ion.


Effect of PEG crystallization on the self-assembly of PEG/peptide copolymers containing amyloid peptide fragments.
The effect of poly(ethylene glycol) PEG crystallization on beta-sheet fibril formation is studied for a series of three peptide/PEG conjugates containing fragments modified from the amyloid beta peptide, specifically KLVFF, FFKLVFF, and AAKLVFF. These are conjugated to PEG with M n = 3300 g mol (-1). It is found, via small-angle X-ray scattering, X-ray diffraction, atomic force microscopy, and polarized optical microscopy, that PEG crystallinity in dried samples can disturb fibrillization, in particular cross-beta amyloid structure formation, for the conjugate containing the weak fibrillizer KLVFF, whereas this is retained for the conjugates containing the stronger fibrillizers AAKLVFF and FFKLVFF. For these two samples, the alignment of peptide fibrils also drives the orientation of the attached PEG chains. Our results highlight the importance of the antagonistic effects of PEG crystallization and peptide fibril formation in PEG/peptide conjugates.


Developmental changes in eyeblink conditioning and neuronal activity in the pontine nuclei.
Neuronal activity was recorded in the pontine nuclei of developing rats during eyeblink conditioning on postnatal days 17-18 (P17-P18) or P24-P25. A pretraining session consisted of unpaired presentations of a 300-msec tone conditioned stimulus (CS) and a 10-msec periorbital shock unconditioned stimulus (US). Five paired training sessions followed the unpaired session, consisting of 100 trials of the CS paired with the US. The rats trained on P24-P25 exhibited significantly more conditioned responses (CRs) than the rats trained on P17-P18, although both groups produced CRs by the end of training. Ontogenetic increases in pre-CS and stimulus-elicited activity in the pontine nuclei were observed during the pretraining session and after paired training. The activity of pontine units was greater on trials with CRs relative to trials without CRs in rats trained on P24-P25, but almost no CR-related modulation was observed in the pontine units of rats trained on P17-P18. The findings indicate that pontine neuronal responses to the CS and modulation of pontine activity by the cerebellum and red nucleus undergo substantial postnatal maturation. The developmental changes in pontine neuronal activity might play a significant role in the ontogeny of eyeblink conditioning.


Fabrication of Stable and Regenerable Amine Functionalized Magnetic Nanoparticles as a Potential Material for Pt(IV) Recovery from Acidic Solutions.
MnFe2O4@SiO2-NH2 magnetic nanocomposite (AFMNC) adsorbent with a particle size of ∼50 nm was successfully synthesized using a facile approach. The as-prepared composite particles showed a fast binding of Pt(IV) with easy magnetic solid-liquid separation. The kinetic data were fitted to both pseudo-first and second-order rate models, indicating that AFMNC exhibited a much higher rate of Pt(IV) binding (0.125 g mg-1 min-1) compared to that of commercial ion-exchange resin Amberjet 4200 (0.0002 g mg-1 min-1). The equilibrium adsorption data were fitted to the Langmuir isotherm model with a relatively high sorption capacity of 380 mg/g. Scanning transmission electron microscopy analysis demonstrated the presence of platinum chloride after sorption on AFMNC, suggesting an adsorbate-adsorbent anion-exchange interaction. In addition, due to its magnetic characteristics, AFMNC can be easily separated from the aqueous medium after the sorption process. The novel nanocomposite may facilitate recovery of Pt(IV) from waste solutions.


Linkage of genes for adult alpha-globin and embryonic alpha-like globin chains.
In alpha-thalassemia, the genetic locus for the alpha chains of adult hemoglobin is not expressed. We have examined the hemoglobins of a number of individual mouse embryos heterozygous for a particular alpha-thalassemia (Hbath-J) and find no decrease in the proportion of hemoglobins containing the alpha chain as compared to the hemoglobin containing the alpha-like embryonic globin chain. This result suggests that the locus for this embryonic alpha-like chain is inactivated or deleted in these embryos as well. Because a single mutational event inactivated adult and embryonic loci, we conclude that they are probably closely linked to one another on the same chromosome. We also present evidence that an unusual hemoglobin in the blood of these embryos is composed only of an embryonic beta-like chain, and is thus analogous to the hemoglobin H (beta 4 tetramer) of adult alpha-thalassemics.


Remote Single-Molecule Switching: Identification and Nanoengineering of Hot Electron-Induced Tautomerization.
Molecular electronics where single molecules perform basic functionalities of digital circuits is a fascinating concept that one day may augment or even replace nowadays semiconductor technologies. The tautomerization of molecules, that is, the bistable functional position of hydrogen protons within an organic frame, has recently been intensively discussed as a potential avenue toward nanoscale switches. It has been shown that tautomerization can be triggered locally or nonlocally, that is, by a scanning tunneling microscope (STM) tip positioned directly above or in close vicinity to the molecule. Whereas consensus exists that local switching is caused by inelastic electrons that excite vibrational molecular modes, the detailed processes responsible for nonlocal tautomerization switching and, even more important in the context of this work, methods to control, engineer, and potentially utilize this process are largely unknown. Here, we demonstrate for dehydrogenated H2Pc molecules on Ag(111) how to controllably decrease or increase the probability of nonlocal, hot electron-induced tautomerization by atom-by-atom designed Ag nanostructures. We show that Ag atom walls act as potential barriers that exponentially damp the hot electron current between the injection point and the molecule, reducing the switching probability by up to 83% for a four-atom wide wall. By placing the molecule in one and the STM tip in the other focal point of an elliptical nanostructure, we could coherently focus hot electrons onto the molecule that led to an almost tripled switching probability. Furthermore, single and double slit experiment based on silver atom structures were used to characterize the spatial extension of hot electron packets. The absence of any detectable interference pattern suggests that the coherence length of the hot electrons that trigger tautomerization processes is rather short. Our results demonstrate that the tautomerization switching of single molecules can remotely be controlled by utilizing suitable nanostructures and may pave the way for designing new tautomerization-based switches.


Echocardiographic assessment of ventricular function in pediatric patients: a comprehensive guide.
Assessment of ventricular function is an important part of every echocardiographic examination. Specific pediatric guidelines on quantification of ventricular function are available, but technology evolves quickly and it generally takes long before newer techniques are integrated into routine clinical practice and are adopted by the guidelines. In the current overview, we would like to present our experience with integrating newer echocardiographic techniques for assessing ventricular function in children using a comprehensive state-of-the-art echocardiographic functional protocol. This protocol is used for specific patient populations such as pediatric patients with cardiomyopathy, post-transplant patients and oncology patients. We present the practical aspects of the protocols, their rationale and how this can be applied in clinical practice.


Radiosensitization with carotid intra-arterial bromodeoxyuridine +/- 5-fluorouracil biomodulation for malignant gliomas.
Bromodeoxyuridine (BUdR), a nonhypoxic radiosensitizing drug, is a halogenated pyrimidine analog that is incorporated into the DNA of dividing cells in a competitive process with thymidine. BUdR sensitizes cells to radiation therapy. 5-Fluorouracil (5-FU) inhibits the endogenous synthesis of thymidine, resulting in increased incorporation of the BUdR. Neurons and glial cells have a very low mitotic rate; they will not incorporate BUdR and will not be sensitized. BUdR and 5-FU are best delivered intra-arterially (IA) because of their regional advantage. We infused BUdR +/- 5-FU over 8 1/2 weeks, before and during 59.4-Gy focal conformal external beam radiation therapy, through a permanently implanted pump with a catheter placed retrograde through the external carotid artery to the carotid bifurcation. Sixty-two patients with grades III or IV glioma were entered into one of two trials, with 23 patients receiving BUdR alone and 39 patients receiving BUdR + 5-FU. The maximum tolerated dose (MTD) of BUdR alone was 400 mg/m2/d for 8 1/2 weeks. The Kaplan-Meier median survival (KMS) was 20 months. In the BUdR + 5-FU trial, the MTD of BUdR was also 400 mg/m2/d and 5-FU was 5 mg/m2/d with a KMS of 17 months. The KMS of all 62 patients in both trials 1 and 2 was 18 months. Pathologic grading used both the original World Health Organization (WHO) and 1993 modified WHO systems. The KMS of grade IV patients was 13.8 months (48 patients) with the original system and 17 months (58 patients) with the modified system.(ABSTRACT TRUNCATED AT 250 WORDS)


A nomogram to predict in-hospital mortality of neonates admitted to the intensive care unit.
To explore the influencing factors for in-hospital mortality in the neonatal intensive care unit (NICU) and to establish a predictive nomogram. Neonatal data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Both univariate and multivariate logit binomial general linear models were used to analyse the factors influencing neonatal death. The area under the receiver operating characteristics (ROC) curve was used to assess the predictive model, which was visualized by a nomogram. A total of 1258 neonates from the NICU in the MIMIC-III database were eligible for the study, including 1194 surviving patients and 64 deaths. Multivariate analysis showed that red cell distribution width (RDW) (odds ratio [OR] 0.813, p=0.003) and total bilirubin (TBIL; OR 0.644, p<0.001) had protective effects on neonatal in-hospital death, while lymphocytes (OR 1.205, p=0.025), arterial partial pressure of carbon dioxide (PaCO2; OR 1.294, p=0.016) and sequential organ failure assessment (SOFA) score (OR 1.483, p<0.001) were its independent risk factors. Based on this, the area under the curve of this predictive model was up to 0.865 (95% confidence interval 0.813 to 0.917), which was also confirmed by a nomogram. The nomogram constructed suggests that RDW, TBIL, lymphocytes, PaCO2 and SOFA score are all significant predictors for in-hospital mortality in the NICU.


Comparisons of acute toxicity of selected chemicals to rainbow trout and rats.
Median lethal concentration (LC50) and dose (LD50) for 217 chemicals were compared over several exposure routes in rainbow trout and rats. Data were compiled primarily from on-line databases and included octanol-water partition coefficient (Kow), trout LC50, and trout and rat LD50 for oral, dermal, and intraperitoneal (i.p.) routes. Kow and molar lethality data were log-transformed for correlation and regression analyses. Median ratios (rat oral LD50/trout LC50 = 156, rat/trout oral LD50 = 0.80, rat/trout dermal LD50 = 0.43, rat/trout i.p. LD50 = 0.55) demonstrated the effect of similar versus dissimilar exposure routes on lethality, reflecting toxicokinetic differences. Simple linear regressions revealed significant correlations (Bonferroni P < 0.05) for trout LC50 versus rat oral LD50 and for trout LD50 versus rat LD50 when matched on exposure route. When Kow was included with multiple regression to consider the effect of hydrophilic/lipophilic partitioning on uptake and toxicity, correlations improved only for trout LC50 versus rat oral LD50 and for trout i.p. LD50 versus rat i.p. LD50. Stratification of data into pesticides and nonpesticides failed to refine prediction of trout LC50 from rat oral LD50. Simple regressions reported here and in the literature relating fish LC50 and rat oral LD50 exhibited varying degrees of correlation (r = 0.26-0.99), reflecting differences in interspecies sensitivity, chemical group evaluated, and experimental methodologies.


Evolution of the Surgical Residency System in Switzerland: An In-Depth Analysis Over 15 Years.
The landscape of surgical training has been subject to many changes over the past 15 years. This study examines resident satisfaction, determinants of satisfaction, demographics, working hours and the teaching rate of common operations in a longitudinal fashion with the aim to identify trends, shortcomings and possible ways to improve the current training system. The Swiss Medical Association administers an annual survey to all Swiss residents to evaluate the quality of postgraduate medical training (yearly respondents: 687-825, response rate: 68-72%). Teaching rates for general surgical procedures were obtained from the Swiss association for quality management in surgery. During the study period (2003-2018), the number of surgical residents (408-655 (+61%)) and graduates in general surgery per year (42-63 (+50%)) increased disproportionately to the Swiss population. While the 52 working hour restriction was introduced in 2005 reported average weekly working hours did not decline (59.9-58.4 h (-3%)). Workplace satisfaction (6 being highest) rose from 4.3 to 4.6 (+7%). Working climate and leadership culture were the main determinants for resident satisfaction. The proportion of taught basic surgical procedures fell from 24.6 to 18.9% (-23%). The number of residents and graduates in general surgery has risen markedly. At the same time, the proportion of taught operations is diminishing. Despite the introduction of working hour restrictions, the self-reported hours never reached the limit. The low teaching rate combined with the increasing resident number represents a major challenge to the maintenance of the current training quality.


Mechanism of action of antiinflammatory drugs.
In 1971, Vane showed that nonsteroid antiinflammatory drugs (NSAIDs) inhibited the biosynthesis of prostaglandins and proposed this as their mechanism of action. Much work around the world has followed. The aspirin-like drugs inhibit the binding of the prostaglandin substrate, arachidonic acid, to the active site of the enzyme. After characterization of the COX-1 enzyme in 1976, a second COX gene was discovered in 1991 encoding for the inducible COX-2. The constitutive isoform of COX, COX-1, has clear physiological functions. The inducible isoform, COX-2, is induced by pro-inflammatory stimuli in migratory cells and inflamed tissues. The range of activities of NSAIDs against COX-1 compared to COX-2 explains the variations in the side effects of NSAIDs at their antiinflammatory doses. Drugs which have the highest potency on COX-2 and less effect on COX-1 will have potent antiinflammatory activity with fewer side effects. All the results published so far support the hypothesis that the unwanted side effects of NSAIDs, such as damage to the gastric mucosa and kidneys, are due to their ability to inhibit COX-1, while their antiinflammatory (therapeutic effects) are due to inhibition of COX-2. Other roles for COX-2 inhibitors will surely be found in the next few years, for prostaglandin formation is under strong control in organs such as the kidney, lungs and uterus. COX-2 is also potently expressed in human colon cancer cells, and NSAIDs delay the progress of colon tumors possibly by causing apoptosis of the tumor cells. The risk of developing Alzheimer's disease, which may involve an inflammatory component, is lessened by chronic ingestion of NSAIDs. The new highly selective inhibitors of COX-2 will not only provide a means of delaying premature labor but will also lead to advances in cancer therapy and protection against Alzheimer's disease.


Pharmacokinetics and milk penetration of ibafloxacin after intravenous administration to lactating goats.
The pharmacokinetic behavior of ibafloxacin was studied after intravenous administration of a single dose of 15 mg/kg to 6 healthy lactating goats. Plasma concentrations of ibafloxacin were determined by high-performance liquid chromatography with fluorescence detection. The data for concentration versus time could best be described by a 2-compartment model. The mean plasma ibafloxacin clearance (and standard error) was 1.05 (0.10) L/h x kg. The mean steady-state volume of distribution was 1.65 (0.42) L/kg. The mean elimination half-life was 3.76 (0.30) h. Ibafloxacin penetration from the blood to the milk was poor. The ratio between the areas under the concentration-time curve of milk and plasma was 0.20 (0.01), indicating scant penetration of ibafloxacin into the milk.


Impaired endothelin calcium signaling coupled to endothelin type B receptors in penile arteries from insulin-resistant obese Zucker rats.
Erectile dysfunction is considered as an early sign of subclinical vascular disease and endothelial dysfunction and a highly prevalent condition in diabetic patients. The current study assessed whether impaired vascular effects of endothelin (ET)-1 may contribute to the vascular dysfunction of penile arteries from a rat model of insulin resistance. The effect of ETA and ETB receptor antagonists was assessed on the intracellular Ca(2+) [Ca(2+) ]i and contractile responses to ET-1 in penile arteries from obese Zucker rats (OZR) and lean Zucker rats (LZR), and ET receptor expression in the arterial wall was assessed by immunohistochemistry. Changes in ET-1 [Ca(2+) ]i and vasoconstriction and ET receptor expression were evaluated in penile arteries from insulin-resistant rats. ET-1-induced vasoconstriction was associated with a higher increase in smooth muscle [Ca(2+) ]i in penile arteries from OZR compared with LZR. Removal of the endothelium inhibited and enhanced contractions to the lowest and highest doses of ET-1, respectively, mainly in OZR. The selective ETA receptor antagonist BQ-123 inhibited ET-1 vasoconstriction and [Ca(2+) ]i response in both LZR and OZR. The ETB receptor antagonist BQ-788 had little effect in healthy arteries but markedly inhibited ET-1-induced increases in [Ca(2+) ]i and vasoconstriction in arteries from OZR. ETA receptors were located on the smooth muscle and endothelium of penile arteries, whereas ETB receptors were found on the arterial endothelium in LZR and OZR, and also on the smooth muscle in OZR, immunostaining for both receptors being higher in OZR. Penile arteries from OZR exhibit an impaired ET-1 Ca(2+) signaling along with changes in the ET receptor profile. Thus, whereas ET-1 contraction and the associated [Ca(2+) ]i increase are mediated by smooth muscle ETA receptors in healthy arteries, ETB receptors contribute to contraction and are coupled to the augmented ET-1 [Ca(2+) ]i response under conditions of insulin resistance.


Long-term effect of 1-piece and 3-piece hydrophobic acrylic intraocular lens on posterior capsule opacification: a randomized trial.
To compare the intensity of posterior capsule opacification (PCO) between the 1-piece and 3-piece haptic designs of the foldable hydrophobic acrylic AcrySof intraocular lens (IOL) over a 5-year period. Randomized, prospective, patient- and examiner-masked clinical trial with intraindividual comparison. Fifty-two patients with bilateral age-related cataract (104 eyes). Each study patient had cataract surgery in both eyes and received a 1-piece AcrySof IOL in 1 eye and a 3-piece AcrySof IOL in the other eye. Follow-up examinations were performed at 1 week, 1 month, 6 months, and 1, 2, and 5 years. Digital retroillumination images were obtained of each eye. The amount of posterior capsule opacification (score range, 0-10) was assessed subjectively at the slit lamp and objectively using automated image analysis software 1, 2, and 5 years after surgery. Posterior capsule opacification score (scale, 0-10). There was no significant difference between the 1-piece and 3-piece AcrySof IOL in best-corrected visual acuity, overlap of rhexis and IOL, capsular folds, anterior capsule opacification, and posterior capsule opacification (1-piece AcrySof PCO score, 1.7+/-1.7; 3-piece AcrySof PCO score, 1.3+/-1.4; P = 0.30). Modification of the IOL haptic design of the sharp optic edged AcrySof IOL from a 3-piece to a 1-piece haptic design caused no significant change in PCO intensity and neodymium:yttrium-aluminium-garnet laser treatment rate 5 years after surgery.


A method for cryopreserving chicken primordial germ cells.
This study established a method for preserving chicken primordial germ cells (PGC) that enables long-term storage in liquid N. Gonads were harvested from stage 27 chick embryos and pooled in groups of 5, 10 (10E), or 20 embryos, contributing gonads to the cell suspension. The gonadal cells, including PGC, were then frozen in 1 of the following cryoprotectant treatments: 2.5% dimethyl sulfoxide (DMSO), 5% DMSO, 10% DMSO, 2.5% ethylene glycol (EG), 5% EG, 10% EG, and 0% cryoprotectant as a control. The cells were liberated and frozen in a biosecure cryopreservation straw at a rate of -1 degrees C/min until reaching -85 degrees C and were then plunged into liquid N (-196 degrees C), in which they were stored until analysis. Flow cytometry was used to analyze the PGC post-thaw. The PGC marker stage-specific embryonic antigen-1, which was detected with goat antimouse IgM fluorescein isothiocyanate, was used to label all PGC, and propidium iodide was used to detect cells with compromised cell membranes. There was an interaction effect for the number of viable PGC per individual embryo (P < or = 0.05). The highest level (183.6 +/- 28.4) of viable PGC per individual embryo was observed for 10% EG with 10E and was significantly higher (P < or = 0.05) than cryopreservation in 2.5% DMSO with 10E and 20 embryos, 2.5% EG with 10E, 5% EG with 10E, and all 0% cryoprotectant treatments. No statistical interaction (P > 0.05) was observed for the percentage of viable PGC. However, the highest percentage (80.6%) was observed at 10% EG with 10E. It was demonstrated that PGC were successfully frozen, and the most effective treatment was 10% EG with 10 embryos/straw.


Fascicle-scale loading and failure behavior of the Achilles tendon.
Although the overall bulk properties of the Achilles tendon have been measured, there is little information detailing the properties of individual fascicles or their interactions. The knowledge of biomechanical properties at the fascicle-scale is critical in understanding the biomechanical behavior of tendons and for the construction of accurate and detailed computational models. Seven tissue samples (approximately 15x4x1 mm(3)) harvested from four freshly thawed human (all male) tendons, each sample having four to six fascicles, were tested in uniaxial tension. A sequential sectioning protocol was used to isolate interaction effects between adjacent fascicles and to obtain the loading response for a single fascicle. The specimen deformation was measured directly using a novel polarized light imaging system with digital image correlation (DIC) for marker-free deformation measurement. The modulus of the single fascicle was significantly higher compared with the intact fascicle group (single: 226 MPa (SD 179), group: 68 MPa (SD 33)). The interaction effect between the adjacent fascicles was less than 10% of the applied load and evidence of sub- and postfailure fascicle sliding was clearly visible. The DIC direct deformation measurements revealed that the modulus of single fascicles could be as much as three to four times the intact specimen. The consistently higher moduli values of the single (strongest) fascicle indicate that the overall response of the tendon may be dominated by a subset of "strongest" fascicles. Also, fascicle-to-fascicle interactions were small, which was <10% of the overall response. This knowledge is useful for developing computational models representing single fascicle and/or fascicle group mechanical behavior and provides valuable insights into fascicle-scale Achilles tendon material properties.


[The prevalence of sleep disorders among adolescents in Cuenca, Spain].
A number of different studies have shown that there is a high prevalence of sleep disorders among adolescents. These are often cited as being due to psychological, hormonal or pubertal factors, as well as inadequate sleep habits. The aims of this study were to determine the prevalence of sleep disorders in the adolescent population and to describe their sleep habits and the relationship between sleep disorders and daytime tiredness or drowsiness. We conducted an epidemiological, observational, cross-sectional study in a sample of schoolchildren studying the 1st and 4th years of compulsory secondary education by means of a self-administered anonymous questionnaire. Insomnia was diagnosed using DSM-IV criteria. Of a total number of 1155 children, 537 were males and 618 were females, with a mean age of 14.03 +/- 1.86 years. They sleep an average of 8 h 18 m during the week and 9 h 40 m at the weekend. Poor quality sleep was reported by 38.55%, 23.1% had difficulty in getting to sleep, 38.2% woke up during the night and 15.9% woke up too early. 17.7% reported some kind of sleep complaint plus some other insomnia-related symptom; the prevalence of insomnia was found to be 9.9%. Snoring (20.5%), talking in their sleep (45.4%) and nightmares (29.5%) were the most frequent parasomnias. 53% of them complained of excessive sleepiness during the day. Insomnia is more frequent in older adolescents, with a family history of similar disorders, among those who smoke and drink and sleep fewer hours at the weekend; those with insomnia present more symptoms of anxiety and depression, as well as more daytime drowsiness. A number of factors are related to the high prevalence of sleep disorders among adolescents, giving rise to their being very tired and drowsy during the day. The interruption of their normal sleep habits at the weekend and an insufficient number of hours' sleep are related to the appearance of insomnia.


[Evaluation of clinical effectiveness of Pazufloxacin Mesilate in acute exacerbation of chronic respiratory diseases].
Patients with chronic respiratory disease have increased susceptibility to infection, because of impairment of the local immunologic defense mechanism in the airway system, which often results in acute exacerbation. Acute exacerbation of chronic respiratory disease is one of the most important predictors of increased morbidity and mortality, and thus the management in the acute phase is essential for better prognosis. Although the clinical guidelines for the management of respiratory tract infections published by the Japanese Respiratory Society recommend administering fluoroquinolones intravenously in case of hospitalized patients, the clinical evidence is still limited. In this study, we evaluated the efficacy of Pazufloxacin Mesilate (PZFX). an intravenous fluoroquinolone. in patients with chronic respiratory diseases complicated with acute exacerbation caused by acute respiratory infections. As a result, 16 out of 18 cases were successfully treated with PZFX. No adverse event was observed during this study. These results may support the validity of administering intravenous fluoroquinolone in hospitalized patients with acute exacerbation caused by infections, as recommended by the Japanese Respiratory Society.


Robotic and laparoscopic partial nephrectomy for T1b tumors.
Laparoscopic and robotic-assisted partial nephrectomy have been widely adopted for the management of small renal masses; however, usage in T1b (greater than 4 cm) lesions is less established. Herein, we report a review on the published series of minimally invasive partial nephrectomies for such renal masses. Several institutions have described laparoscopic and robotic-assisted partial nephrectomy as a safe management option for pathologic T1b lesions. The oncologic results are promising, with low positive margin rates and few cases of progressive disease. Longer-term renal dysfunction does not appear at an increasing rate in this cohort of patients. The safety profile appears acceptable; however, there is a slightly increased rate of complications in these cohorts of patients. Laparoscopic and robotic-assisted partial nephrectomy is a well tolerated and viable option for performing minimally invasive surgical extirpation of cT1b renal masses. The oncologic and functional results are excellent with acceptable safety profiles. In patients with such masses minimally invasive partial nephrectomy should be considered for elective and absolute indications. In order to achieve excellent functional and oncologic outcomes with minimal perioperative complications an experienced surgeon with assistant and assessment of tumor with patient comorbidities are important.


Synthesis and biological evaluation of a new acyclic pyrimidine derivative as a probe for imaging herpes simplex virus type 1 thymidine kinase gene expression.
With the idea of finding a more selective radiotracer for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression by means of positron emission tomography (PET), a novel [¹⁸F]fluorine radiolabeled pyrimidine with 4-hydroxy-3-(hydroxymethyl)butyl side chain at N-1 (HHB-5-[¹⁸F]FEP) was prepared and evaluated as a potential PET probe. Unlabeled reference compound, HHB-5-FEP, was synthesized via a five-step reaction sequence starting from 5-(2-acetoxyethyl)-4-methoxypyrimidin-2-one. The radiosynthesis of HHB-[¹⁸F]-FEP was accomplished by nucleophilic radiofluorination of a tosylate precursor using [¹⁸F]fluoride-cryptate complex in 45% ± 4 (n = 4) radiochemical yields and high purity (>99%). The biological evaluation indicated the feasibility of using HHB-5-[¹⁸F]FEP as a PET radiotracer for monitoring HSV1-tk expression in vivo.


The emergence of new prognostic scores in lung cancer patients with spinal metastasis: A 12-year single-center retrospective study.
Objective: Lung cancer patients exhibit spinal metastases from a specific population, and with this study, we aimed to develop a model that can predict this particular group's survival. Methods: Data were retrospectively collected from 83 lung cancer patients who underwent spinal metastasis surgery at our center from 2009 to 2021. After the initial assessment of treatment and scoring effects, a nomogram for survival prediction was created by identifying and integrating critical prognostic factors, followed by a consistency index (C-index) to measure consistency, and finally, a subject working characteristic curve (ROC) to compare the predictive accuracy of the three existing models. Results: The mean postoperative survival was 14.7 months. Surgical treatment significantly improved the VAS and Frankel scores in lung cancer patients with spinal metastases. The revised Tokuhashi score underestimated the life expectancy of these patients. Six independent prognostic factors, including age, extraspinal bone metastasis foci, visceral metastasis, Frankel score, targeted therapy, and radiotherapy, were identified and incorporated into the model. Calibration curves for 3-, 6-, and 12-month overall survival showed a good concordance between predicted and actual risk. The nomogram C-index for the cohort study was 0.800 (95% confidence interval [CI]: 0.757-0.843). Model comparisons showed that the nomogram's prediction accuracy was better than revised Tokuhashi and Bauer's scoring systems. Conclusions: Spine surgery offered patients the possibility of regaining neurological function. Having identified shortcomings in existing scoring systems, we have recreated and validated a new nomogram that can be used to predict survival outcomes in patients with spinal metastases from lung cancer, thereby assisting spinal surgeons in making surgical decisions and personalizing treatment for these patients.


Transparent and tough bulk composites inspired by nacre.
Materials combining optical transparency and mechanical strength are highly demanded for electronic displays, structural windows and in the arts, but the oxide-based glasses currently used in most of these applications suffer from brittle fracture and low crack tolerance. We report a simple approach to fabricate bulk transparent materials with a nacre-like architecture that can effectively arrest the propagation of cracks during fracture. Mechanical characterization shows that our glass-based composites exceed up to a factor of 3 the fracture toughness of common glasses, while keeping flexural strengths comparable to transparent polymers, silica- and soda-lime glasses. Due to the presence of stiff reinforcing platelets, the hardness of the obtained composites is an order of magnitude higher than that of transparent polymers. By implementing biological design principles into glass-based materials at the microscale, our approach opens a promising new avenue for the manufacturing of structural materials combining antagonistic functional properties.


Febrile patients admitted to remote hospitals in Northeastern Kenya: seroprevalence, risk factors and a clinical prediction tool for Q-Fever.
Q fever in Kenya is poorly reported and its surveillance is highly neglected. Standard empiric treatment for febrile patients admitted to hospitals is antimalarials or penicillin-based antibiotics, which have no activity against Coxiella burnetii. This study aimed to assess the seroprevalence and the predisposing risk factors for Q fever infection in febrile patients from a pastoralist population, and derive a model for clinical prediction of febrile patients with acute Q fever. Epidemiological and clinical data were obtained from 1067 patients from Northeastern Kenya and their sera tested for IgG antibodies against Coxiella burnetii antigens by enzyme-linked-immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA) and quantitative real-time PCR (qPCR). Logit models were built for risk factor analysis, and diagnostic prediction score generated and validated in two separate cohorts of patients. Overall 204 (19.1 %, 95 % CI: 16.8-21.6) sera were positive for IgG antibodies against phase I and/or phase II antigens or Coxiella burnetii IS1111 by qPCR. Acute Q fever was established in 173 (16.2 %, 95 % CI: 14.1-18.7) patients. Q fever was not suspected by the treating clinicians in any of those patients, instead working diagnosis was fever of unknown origin or common tropical fevers. Exposure to cattle (adjusted odds ratio [aOR]: 2.09, 95 % CI: 1.73-5.98), goats (aOR: 3.74, 95 % CI: 2.52-9.40), and animal slaughter (aOR: 1.78, 95 % CI: 1.09-2.91) were significant risk factors. Consumption of unpasteurized cattle milk (aOR: 2.49, 95 % CI: 1.48-4.21) and locally fermented milk products (aOR: 1.66, 95 % CI: 1.19-4.37) were dietary factors associated with seropositivity. Based on regression coefficients, we calculated a diagnostic score with a sensitivity 93.1 % and specificity 76.1 % at cut off value of 2.90: fever >14 days (+3.6), abdominal pain (+0.8), respiratory tract infection (+1.0) and diarrhoea (-1.1). Q fever is common in febrile Kenyan patients but underappreciated as a cause of community-acquired febrile illness. The utility of Q fever score and screening patients for the risky social-economic and dietary practices can provide a valuable tool to clinicians in identifying patients to strongly consider for detailed Q fever investigation and follow up on admission, and making therapeutic decisions.


Direct block of human ether-a-go-go-related gene potassium channels by caffeine.
The human ether-a-go-go-related gene (hERG) potassium channel is expressed in a variety of cell types, including neurons, tumor cells, and cardiac myocytes. In the heart, it is important for repolarization of the cardiac action potential. Attenuation of hERG current can cause long QT syndrome and cardiac arrhythmias such as torsades de pointes. Caffeine is frequently used as a pharmacological tool to study calcium-dependent transduction pathways in cellular preparations. It raises cytosolic calcium by opening ryanodine receptors and may also inhibit phosphodiesterases to increase cytosolic cAMP. In this study, we show 5 mM caffeine rapidly and reversibly attenuates hERG currents expressed in human embryonic kidney 293 cells to 61.1 +/- 2.2% of control. Caffeine-dependent inhibition of hERG current is not altered by raising cAMP with forskolin, buffering cytosolic calcium with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, or inhibition of protein kinase C. Thus, the effects of caffeine are unlikely to be mediated by cAMP or intracellular calcium-dependent mechanisms. Further experiments showed caffeine directly blocks hERG in an open state-dependent manner. Furthermore, caffeine inhibition is greatly reduced by the pore mutants Y562A and F656A hERG, which disrupt block of most previously tested hERG antagonists. Thus, caffeine attenuates hERG currents by binding to a drug receptor located within the inner cavity of the channel. Dietary intake of caffeine is unlikely to cause long QT syndrome because plasma concentrations do not reach sufficiently high levels to significantly inhibit hERG currents. However, the effects of caffeine have implications for its use in examining calcium-dependent pathways in cellular preparations expressing hERG.


Cerebellar low-grade oligoastrocytoma presenting with subarachnoid haemorrhage.
Subarachnoid haemorrhage (SAH) associated with intra-axial tumours is extremely uncommon and is usually seen in association with intratumoural bleed. Tumours located near the ventricle or subarachnoid spaces have a higher propensity for SAH compared to intraparenchymal lesions. Low-grade tumours rarely demonstrate any evidence of bleed on imaging. Oligoastrocytomas of the posterior fossa are rare tumours in adults and their presentation with intratumoural haemorrhage and SAH is unknown. We report a unique case of cerebellar low-grade oligoastrocytoma that mimicked a tentorial-based extraaxial lesion on imaging and presented with SAH. Susceptibility-weighted magnetic resonance imaging is a useful imaging modality to demonstrate blood within and outside the tumour.


Cardiogenic shock associated with subarachnoid hemorrhage.
Systemic complications are frequent in subarachnoid hemorrhage patients. Among these complications, electrocardiographic abnormalities simulating ischemic cardiomyopathy may occur, possibly associated with myocardial dysfunction. This manuscript aims to report a case of subarachnoid hemorrhage associated with myocardial dysfunction and cardiogenic shock. A 45 years old woman was admitted with subarachnoid hemorrhage and coma, showing Glasgow scale = 7, Hunt-Hess = 5 and Fischer computed tomography classification = 3. On the second day, the patient underwent anterior cerebral communicant artery aneurysm embolization. The clinical evaluation revealed diffuse pulmonary infiltration, dyspnea and hypotension. Additional tests showed electrocardiographic lateral wall repolarization changes and elevated creatine kinase-MB fraction (36U/L). The cardiac index was 2.03 L/minute/m², Vascular systemic resistance was 3728 dynes.sec/cm². The non-responsiveness to volume demonstrated a cardiogenic shock pattern. The ventricular ejection fraction was 39%. The coronariography was normal, showing no obstructive lesions. Six days later the patient was removed from respiratory support and after eight days the dobutamine infusion was discontinued. The ejection fraction recovered up to 65%. Serial transcranial Doppler evaluations did not show vascular spasm. After ten days the patient was discharged from the intensive care unit. Patients with subarachnoid hemorrhage may be complicated with ventricular dysfunction and cardiogenic shock, increasing the cerebral ischemia risk. Diagnosis optimization and hemodynamic stabilization are essential to minimize the risk of cerebral vasospasm and ischemia.


RETRACTED ARTICLE: Secukinumab-induced paradoxical skin lesions, but successful treatment with tofacitinib in SAPHO syndrome: a case report.
We, the Editors and Publisher of Journal of Dermatological Treatment, have retracted the following article:Li Luan & Chengzhi Lv (2023) Secukinumab-induced paradoxical skin lesions, but successful treatment with tofacitinib in SAPHO syndrome: a case report, Journal of Dermatological Treatment, DOI: 10.1080/09546634.2023.2193662Since publication of the article, concerns were raised by a reader regarding the lack of recorded patient consent to publish. Upon further investigation, it was determined that written consent for the publication was not obtained by the authors. The authors were contacted for an explanation and confirmed written consent for the publication was not obtained.As this represents a breach of the journal's editorial policies, we are therefore retracting the article. The corresponding author listed in this publication has been informed.We have been informed in our decision-making by our editorial policies and the COPE guidelines.The retraction article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted'.


Engineering Nitrogenases for Synthetic Nitrogen Fixation: From Pathway Engineering to Directed Evolution.
Globally, agriculture depends on industrial nitrogen fertilizer to improve crop growth. Fertilizer production consumes fossil fuels and contributes to environmental nitrogen pollution. A potential solution would be to harness nitrogenases-enzymes capable of converting atmospheric nitrogen N2 to NH3 in ambient conditions. It is therefore a major goal of synthetic biology to engineer functional nitrogenases into crop plants, or bacteria that form symbiotic relationships with crops, to support growth and reduce dependence on industrially produced fertilizer. This review paper highlights recent work toward understanding the functional requirements for nitrogenase expression and manipulating nitrogenase gene expression in heterologous hosts to improve activity and oxygen tolerance and potentially to engineer synthetic symbiotic relationships with plants.


Use of and attitudes towards emergency contraception: a survey of women in five European countries.
To identify knowledge of and attitudes towards emergency contraception (EC) in women from five European countries. In an internet-based survey, sexually active women aged 16 to 46 years from France, Germany, Italy, Spain, and the UK were asked about their use of and opinions on EC. Overall, 7170 women completed the survey. Thirty percent reported having had unprotected sexual intercourse during the previous 12 months (population at risk). Twenty-four percent of the population at-risk reported using EC. The most common reasons given for not using EC were: not perceiving themselves to be at risk of pregnancy; and not thinking about EC as an option. A third of respondents indicated they did not know how EC works, with several misconceptions about EC noted e.g., leading to infertility, similar to abortion. Seventy-nine percent of women agreed that EC is a responsible choice to prevent unwanted pregnancy, but nearly a third of women who used EC felt uncomfortable or judged when obtaining it. EC is underutilised by three-quarters of the women surveyed. Women do not recognise they may be at risk of pregnancy when contraception fails. There are still several misbeliefs about EC indicating a need for better education of the public.


Fast compressive beamforming with a modified fast iterative shrinkage-thresholding algorithm.
Compressive beamforming has been successfully applied to direction-of-arrival estimation with sensor arrays. The results demonstrated that this technique achieves superior performance when compared with traditional high-resolution beamforming methods. The existing compressive beamforming methods use classical iterative optimization algorithms in their compressive sensing theories. However, the computational complexity of the existing compressive beamforming methods tend to be excessively high, which has limited the use of compressive beamforming in applications with limited computing resources. To address this issue, this paper proposes a fast compressive beamforming method which combines the shift-invariance of the array beam patterns with a fast iterative shrinkage-thresholding algorithm. The evaluation shows that the proposed fast compressive beamforming method successfully reduces the number of floating-point operations by 3 orders of magnitude when compared with the existing methods. In addition, both the simulations and experiments demonstrate that the resolution limit for discerning closely spaced sources of the introduced fast method is comparable to those of the existing compressive beamforming methods, which use classical iterative optimization algorithms.


NTRK2-related developmental and epileptic encephalopathy: Report of 5 new cases.
This study aimed to describe the phenotype of five new cases of NTRK2-related developmental and epileptic encephalopathy (DEE). The clinical features, EEG, neuroimaging and genetics were reviewed for cases with likely pathogenic and pathogenic NTRK2 variants and then summarized. Five cases of NTRK2-related DEE were identified. Four had a previously described recurrent variant in NTRK2 and one had a novel variant. The phenotype was characterized by early- onset seizures (infantile spasms, later evolving to multifocal seizures), global developmental delay, variable movement disorders, microcephaly and optic nerve hypoplasia. This series further expands our knowledge of the phenotype and genotype of NTRK2-related DEE.


Effect of DNA base sequence on the configuration of deoxyadenosine adducts formed by the Fjord region diol epoxide, (+)-(1R,2S,3R,4S)-3,4-dihydroxy-1,2-epoxy-1,2,3,4- tetrahydrobenzo[c]phenanthrene.
The carcinogen (+)-(1R,2S,3R,4S)-3,4-dihydroxy-1,2-epoxy-1,2,3,4- tetrahydrobenzo[c]phenanthrene (in which the 4-OH group and epoxide oxygen are cis) was reacted with duplexes formed from self-complementary oligodeoxyribonucleotides, producing 1S or 1R configured adducts through trans or cis epoxide ring opening, respectively, by the exocyclic amino group of a central target A. Sequences containing 5'-AT-3' generated much higher S vs R ratios than the average of 3.38 observed with calf thymus DNA samples, while sequences containing 5'-TA-3' generated much lower ratios. Sequences with G in the position immediately 5' to the central AT or TA, and C in the position immediately 3', generated moderately higher ratios than did sequences with adjacent 5'C and 3'G. When thymidine was replaced by deoxyuridine in several sequences, the ratios of S vs R configured dA adducts and dA adducts vs dG adducts were substantially and uniformly reduced, but otherwise varied with the choice of nearest neighbors in patterns similar to those observed with the T containing sequences. Two hypothetical mechanisms are proposed to explain the effect of nearest neighbors on the S vs R dA adduct ratio; in both, diol epoxide intercalation precedes covalent bonding. In one mechanism, intercalation to the 5' side of the target A yields an S adduct while intercalation to the 3' side yields an R adduct, and the extent of adduct formation follows the nearest neighbor series G > C > T.(ABSTRACT TRUNCATED AT 250 WORDS)


Thermodynamic Insights for Electrochemical Hydrogen Compression with Proton-Conducting Membranes.
Membrane electrode assemblies (MEA) based on proton-conducting electrolyte membranes offer opportunities for the electrochemical compression of hydrogen. Mechanical hydrogen compression, which is more-mature technology, can suffer from low reliability, noise, and maintenance costs. Proton-conducting electrolyte membranes may be polymers (e.g., Nafion) or protonic-ceramics (e.g., yttrium-doped barium zirconates). Using a thermodynamics-based analysis, the paper explores technology implications for these two membrane types. The operating temperature has a dominant influence on the technology, with polymers needing low-temperature and protonic-ceramics needing elevated temperatures. Polymer membranes usually require pure hydrogen feed streams, but can compress H 2 efficiently. Reactors based on protonic-ceramics can effectively integrate steam reforming, hydrogen separation, and electrochemical compression. However, because of the high temperature (e.g., 600 ° C) needed to enable viable proton conductivity, the efficiency of protonic-ceramic compression is significantly lower than that of polymer-membrane compression. The thermodynamics analysis suggests significant benefits associated with systems that combine protonic-ceramic reactors to reform fuels and deliver lightly compressed H 2 (e.g., 5 bar) to an electrochemical compressor using a polymer electrolyte to compress to very high pressure.


Pathogenic factors of Pseudomonas aeruginosa - the role of biofilm in pathogenicity and as a target for phage therapy.
Pseudomonas aeruginosa is an opportunistic pathogen that can cause several acute and chronic infections in humans, and it has become an important cause of nosocomial infections and antibiotic resistance. Biofilm represents an important virulence factor for these bacteria, plays a role in P. aeruginosa infections and avoidance of immune defence mechanisms, and has the ability to protect the bacteria from antibiotics. Alginate, Psl and Pel, three exopolysaccharides, are the main components in biofilm matrix, with many biological functions attributed to them, especially with respect to the protection of the bacterial cell from antibiotics and the immune system. Pseudomonas infections, biofilm formation and development of resistance to antibiotics all require better understanding to achieve the best results using alternative treatment with phage therapy. This review describes the P. aeruginosa pathogenicity and virulence factors with a special focus on the biofilm and its role in infection and resistance to antibiotics and summarizes phage therapy as an alternative approach in treatment of P. aeruginosa infections.


Future land-use change and its impact on terrestrial ecosystem carbon pool evolution along the Silk Road under SDG scenarios.
Sustainable development goals (SDGs) in the United Nations 2030 Agenda call for action by all nations to promote economic prosperity while protecting the planet. Projection of future land-use change under SDG scenarios is a new attempt to scientifically achieve the SDGs. Herein, we proposed four scenario assumptions based on the SDGs, including the sustainable economy (ECO), sustainable grain (GRA), sustainable environment (ENV), and reference (REF) scenarios. We forecasted land-use change along the Silk Road (resolution: 300 m) and compared the impacts of urban expansion and forest conversion on terrestrial carbon pools. There were significant differences in future land use change and carbon stocks, under the four SDG scenarios, by 2030. In the ENV scenario, the trend of decreasing forest land was mitigated, and forest carbon stocks in China increased by approximately 0.60% compared to 2020. In the GRA scenario, the decreasing rate of cultivated land area has slowed down. Cultivated land area in South and Southeast Asia only shows an increasing trend in the GRA scenario, while it shows a decreasing trend in other SDG scenarios. The ECO scenario showed highest carbon losses associated with increased urban expansion. The study enhances our understanding of how SDGs can contribute to mitigate future environmental degradation via accurate simulations that can be applied on a global scale.


Comprehensive analyses of T-UCR expression profiles and exploration of the efficacy of uc.63- and uc.280+ as biomarkers for lung cancer in Xuanwei, China.
Lung cancer in Xuanwei (LCXW), China, is known worldwide for occurring frequently with high morbidity and mortality, which necessitates research to determine its pathogenesis. This study attempted to screen potential transcribed ultraconserved region (T-UCR) biomarkers related to LCXW. We performed T-UCR microarrays on 26 paired lung adenocarcinoma and adjacent tissues to explore the T-UCR expression profile of LCXW. Then, bioinformatics analysis was carried out to identify potential T-UCRs, which were further validated by real-time quantitative PCR (RT-qPCR). Then, clinical relevance analysis and Kaplan-Meier tests were performed on 50 paired tissues. T-UCRs and RNA transcripts whose transcription units overlap UCRs (RTOUs) were significantly dysregulated in LCXW tissues compared with the corresponding noncancerous lung (NCL) tissues and presented an increasing trend from stage I to III. The expression between T-UCRs and host genes or flanking genes presented a positive or negative correlation. RT-qPCR analysis showed that uc.63- and uc.280+ were significantly up-regulated in LCXW tissues (P < 0.05). Uc.63- up-regulation was associated with tumor stage and poor prognosis of patients (P < 0.05), and uc.280+ up-regulation was associated with patient age (P < 0.05). Bioinformatics analysis of RTOUs showed that the transcripts of XPO1, uc002sbh and uc002sbg, were potentially regulated targets of uc.63-. Gene Ontology and pathway analyses showed XPO1 was involved in many important biological functions. This study depicted T-UCR and RTOU expression profiling of LCXW and revealed some potential T-UCR biomarkers that may be involved in the carcinogenesis of LCXW.


LncRNA MALAT1 expression inhibition suppresses tongue squamous cell carcinoma proliferation, migration and invasion by inactivating PI3K/Akt pathway and downregulating MMP-9 expression.
LncRNA MALAT1 has been proved to be involved in the development of various types of human cancers while the involvement of MALAT1 in tongue squamous cell carcinoma has not been reported. In view of this, our study aimed to investigate the functionality of MALAT1 in tongue squamous cell carcinoma. The expression of MALAT1 in tumor tissues and adjacent healthy tissues of tongue cancer patients, and the serum from tongue cancer patients as well as healthy controls, were detected by quantitative Real Time-PCR (qRT-PCR). ROC curve analysis was performed to analyze the diagnostic value of plasma MALAT1 for tongue cancer. Survival curves were plotted using the Kaplan-Meier method to evaluate the prognostic value of plasma MALAT1 for tongue cancer. CCK-8 assay, transwell migration and invasion assay were performed to investigate the effects of MALAT1 knockdown on the proliferation, migration and invasion of tongue cancer cells, respectively. The effects of MALAT1 overexpression on the PI3K/Akt pathway and MMP-9 expression were detected by Western blot. The expression level of MALAT1 was remarkably higher in tumor tissues than that in adjacent healthy tissues. Serum MALAT1 was significantly higher in tongue cancer patients than in healthy controls. MALAT1 knockdown markedly inhibits the proliferation, migration and invasion of tongue cancer cells. MALAT1 knockdown also reduced the phosphorylation level of Akt as well as the expression level of MMP-9. It showed no significant effects on Akt expression, while PI3K activator treatment reduced the inhibitory effects of MALAT1 knockdown on the proliferation, migration and invasion of tongue cancer cells. LncRNA MALAT1 expression inhibition can inhibit the proliferation, migration and invasion of tongue cancer cells by inactivating the PI3K/Akt pathway and downregulating MMP-9. MALAT1 may serve as a target for the treatment of tongue squamous cell carcinoma.


Abrikossoff cell tumor of the oesophagus: a case report and review of the literature.
Abrikossoff tumours or granular cell tumours are rare and usually benign tumours. The oesophagus is a rare location (0.001% of all tumours). The macroscopic appearance is typical (yellow, firm, well circumscribed submucosal neoplasm-like with reduced vascular patterns) but due to the rarity of this lesion, it can be mistaken with other similar lesions. This is the report of a case of a 47-year-old female with a granular cell tumour of the distal oesophagus. In this case, the Abrikossoff tumour is clinically, radiologically en histologically benign. According to the fact that there is low evidence in the literature for removing such Lesions in patient without symptoms, it was decided to be conservative. In this paper we discuss the case with review of the Literature with emphasis on the diagnosis, evaluation and management.


Ventriculoatrial shunt catheter displacement in a child with partial anomalous pulmonary venous return: case report.
Ventriculoatrial (VA) shunts remain the most used alternative to ventriculoperitoneal shunts in infants with hydrocephalus. The authors report a case of an acute VA shunt malfunction as a result of distal catheter displacement in an 18-month-old girl with partial anomalous pulmonary venous return. The child presented with respiratory compromise, and a chest radiograph revealed a lung infiltrate and normal position of the distal shunt catheter tip. Computed tomography demonstrated stable ventricle size in comparison with previous studies. As the patient's respiratory distress progressed, she required intubation, mechanical ventilation with high airway pressures and inspired oxygen concentrations, muscle relaxants, and sedation. A routine morning chest radiograph several days after admission revealed displacement of the distal catheter into the left innominate vein. Later that day the child's pupils were noted to be large and unreactive and a distal shunt malfunction was diagnosed. Complications of VA shunts and the presumed mechanism by which the catheter became displaced are discussed.


A Novel Family of Small Molecules that Enhance the Intracellular Delivery and Pharmacological Effectiveness of Antisense and Splice Switching Oligonucleotides.
The pharmacological effectiveness of oligonucleotides has been hampered by their tendency to remain entrapped in endosomes, thus limiting their access to cytosolic or nuclear targets. We have previously reported a group of small molecules that enhance the effects of oligonucleotides by causing their release from endosomes. Here, we describe a second novel family of oligonucleotide enhancing compounds (OECs) that is chemically distinct from the compounds reported previously. We demonstrate that these molecules substantially augment the actions of splice switching oligonucleotides (SSOs) and antisense oligonucleotides (ASOs) in cell culture. We also find enhancement of SSO effects in a murine model. These new compounds act by increasing endosome permeability and causing partial release of entrapped oligonucleotides. While they also affect the permeability of lysosomes, they are clearly different from typical lysosomotropic agents. Current members of this compound family display a relatively narrow window between effective dose and toxic dose. Thus, further improvements are necessary before these agents can become suitable for therapeutic use.


Membranous glomerulonephritis in a patient with an adrenal ganglioneuroma.
Membranous glomerulonephritis has been reported in association with several tumors. This report is the first case of membranous glomerulonephritis associated with an adrenal ganglioneuroma. The sera obtained from the patient at presentation stained the fibrillary component of the ganglioneuroma and the glomerular basement membrane of the kidney. The antibodies present in the patient's serum also reacted with the glomerular basement membrane of several normal and randomly selected abnormal kidneys, including 1 from a patient with Alport's syndrome. The patient's sera contained a circulating tumor antigen-specific antibody that cross-reacted with an antigen present on the podocyte membrane of the renal glomeruli. The resection of the ganglioneuroma resulted in a complete remission of the nephrotic syndrome within months of removal of the tumor. This was associated with loss of antibodies in the patient's serum. The patient was not treated with steroids or any immunosuppressive agents. The patient remains in remission with normal renal function after 9 years of follow-up.


Characteristics of beta-lactoglobulin binding to the all-trans-retinal moiety covalently immobilized on Celite.
All-trans-retinal was covalently immobilized on Celite and investigated as a bioselective adsorption matrix for beta-lactoglobulin. Two types of Celite supports were compared, indicating the best performance with 100/120 mesh, type R648. The R648 matrix yielded a high concentration (9.2 mumol/ml) of the ligand when the derivative was produced, and the derivatized matrix exhibited the best retention of beta-lactoglobulin. Binding of beta-lactoglobulin to the immobilized trans-retinal matrix is biospecific, but the affinity is dependent on pH and ionic strength. alpha-Lactalbumin is not bound to this bioselective adsorbant, so its elution was not retarded or affected by pH or buffer concentration. Affinity for beta-lactoglobulin was optimal at pH 5.14; a dissociation constant of 2.7 microM was obtained in .1 M buffer solutions. At pH 7.0, the affinity decreased 44-fold, and, below pH 3.5, no binding occurred. The estimated loading capacity based on chromatographic data was approximately 14 g/L (.75 mumol/ml) of support.


Issues and opportunities of digital phenotyping: ecological momentary assessment and behavioral sensing in protecting the young from suicide.
Digital phenotyping refers to the collection of real-time biometric and personal data on digital tools, mainly smartphones, and wearables, to measure behaviors and variables that can be used as a proxy for complex psychophysiological conditions. Digital phenotyping might be used for diagnosis, clinical assessment, predicting changes and trajectories in psychological clinical conditions, and delivering tailored interventions according to individual real-time data. Recent works pointed out the possibility of using such an approach in the field of suicide risk in high-suicide-risk patients. Among the possible targets of such interventions, adolescence might be a population of interest, since they display higher odds of committing suicide and impulsive behaviors. The present work systematizes the available evidence of the data that might be used for digital phenotyping in the field of adolescent suicide and provides insight into possible personalized approaches for monitoring and treating suicidal risk or predicting risk trajectories. Specifically, the authors first define the field of digital phenotyping and its features, secondly, they organize the available literature to gather all the digital indexes (active and passive data) that can provide reliable information on the increase in the suicidal odds, lastly, they discuss the challenges and future directions of such an approach, together with its ethical implications.


[Hypertriglyceridemia and plasma insulin in combined familial hyperlipidemia].
Changes in insulin secretion were investigated in a group of non obese subjects with combined familial hyperlipidemia (CFH), with normal glucose tolerance, relating the observed changes with plasma triglycerides and lipoprotein phenotype. The study was conducted with 21 subjects (16 males and 5 females; mean age: 45.9 +/- 9.1 years), diagnosed of CFH after the clinical and analytical study of patients and their first degree relatives (9 with phenotype IIa, 8 IIb, and 4 IV) and 21 healthy control subjects, of similar age, sex and body weight. In both groups, lipids, plasma lipoproteins, glucose, basal plasma insulin, and insulin after and oral glucose overload (OGO) were quantitated. Diastolic blood pressure was higher (p < 0.01) in CFH group compared with controls (means: 132/80 vs 123/71 mmHg, respectively). TC, TG and Apo B were also higher in the CFH group. With OGO significantly higher serum insulin levels were observed at 0, 30, 60, 90 and 120 minutes in CFH subjects compared with control group. Basal serum insulin and the area under the curve of insulin secretion after OGO was higher in subjects with triglycerides (45,579 +/- 13,056 in controls, 61,385 +/- 22,254 in CFH IIa, 70,645 +/- 17,271 IIb and 124,884 +/- 36,944 in CFH IV. Insulin secretion correlated significantly (p < 0.01) with plasma triglycerides. As conclusion, hyperinsulinism is a finding in CFH non obese subjects and with normal glucose tolerance, and has an increasing frequency in subjects with high triglycerides levels.


Studies in potential filaricides. 6. Synthesis of 3,8-disubstituted 1,3,8-triazabicyclo(4.4.0)decan-2-ones and -thiones.
1,3,8-Triazabicyclo[4.4.0]decan-2-ones and -thiones varying substituents at positions 3 and 8 have been synthesized. When tested in cotton rats for their antifilarial activity against Litomosoides carinii, some of the compounds showed moderate microfilaricidal activity.


Efficient light harvesting and energy transfer in a red phosphorescent iridium dendrimer.
A series of red phosphorescent iridium dendrimers of the type [Ir(btp)2(pic-PCn)] (Ir-Gn; n = 0, 1, 2, and 3) with two 2-(benzo[b]thiophen-2-yl)pyridines (btp) and 3-hydroxypicolinate (pic) as the cyclometalating and ancillary ligands were prepared in good yields. Dendritic generation was grown at the 3 position of the pic ligand with 4-(9H-carbazolyl)phenyl dendrons connected to 3,5-bis(methyleneoxy)benzyloxy branches (PCn; n = 0, 2, 4, and 8). The harvesting photons on the PCn dendrons followed by efficient energy transfer to the iridium center resulted in high red emissions at ∼600 nm by metal-to-ligand charge transfer. The intensity of the phosphorescence gradually increased with increasing dendrimer generation. Steady-state and time-resolved spectroscopy were used to investigate the energy-transfer mechanism. On the basis of the fluorescence quenching rate constants of the PCn dendrons, the energy-transfer efficiencies for Ir-G1, Ir-G2, and Ir-G3 were 99, 98, and 96%, respectively. The energy-transfer efficiency for higher-generation dendrimers decreased slightly because of the longer distance between the PC dendrons and the core iridium(III) complex, indicating that energy transfer in Ir-Gn is a Förster-type energy transfer. Finally, the light-harvesting efficiencies for Ir-G1, Ir-G2, and Ir-G3 were determined to be 162, 223, and 334%, respectively.


Effect of clavulanic acid on the activities of ten beta-lactam agents against members of the Bacteroides fragilis group.
Clavulanic acid reduced the MICs of amoxicillin, carbencillin , cefamandole, cefotaxime, ceftazidime, ceftizoxime, cephalothin, and penicillin G, but not of cefoxitin or moxalactam, against 77 isolates of the Bacteroides fragilis group, all rapidly beta-lactamase positive by the nitrocefin slide test. It had no effect on the susceptibilities of eight Bacteroides distasonis strains that were slowly beta-lactamase positive (18 h of incubation).


Double-Stranded RNA Sensors and Modulators in Innate Immunity.
Detection of double-stranded RNAs (dsRNAs) is a central mechanism of innate immune defense in many organisms. We here discuss several families of dsRNA-binding proteins involved in mammalian antiviral innate immunity. These include RIG-I-like receptors, protein kinase R, oligoadenylate synthases, adenosine deaminases acting on RNA, RNA interference systems, and other proteins containing dsRNA-binding domains and helicase domains. Studies suggest that their functions are highly interdependent and that their interdependence could offer keys to understanding the complex regulatory mechanisms for cellular dsRNA homeostasis and antiviral immunity. This review aims to highlight their interconnectivity, as well as their commonalities and differences in their dsRNA recognition mechanisms.


[Heredity and colorectal cancer].
The authors underline the role of inheritance in colorectal cancer and reporting the genealogical study of two families with high incidence of colorectal cancers personally observed. They thought that the genetic endowment (oncogenes, suppressor genes, microsatellite instability, protein-kinase C) was implicated directly in the genesis of disease.


Arch-width changes in extraction vs nonextraction treatments in matched Class I borderline malocclusions.
The aims of this study were to identify a sample of borderline Class I extraction and nonextraction patients and to investigate posttreatment changes in arch-width and perimeter measurements. A parent sample of 580 Class I patients was subjected to discriminant analysis, and a borderline subsample of 62 patients, 31 treated with extraction of 4 first premolars and 31 treated without extractions, was obtained. The patients' plaster casts were digitally scanned, and the maxillary and mandibular intercanine and intermolar widths and perimeters were assessed. The extraction group showed increases in maxillary and mandibular intercanine widths (P <0.001) and decreases in mandibular intermolar width and in maxillary and mandibular perimeters (P <0.001). The nonextraction group showed increases in all 4 arch-width measurements (P ≤0.003), whereas the maxillary and mandibular perimeters were maintained. The posttreatment differences between the 2 groups showed significant differences in the maxillary (P <0.001) and mandibular intermolar widths (P <0.001). Also, the comparison of the arch perimeters between the 2 treatment groups showed adjusted differences of -8.51 mm (P <0.001) and -8.44 mm (P <0.001) for the maxillary and mandibular arches, respectively. The intercanine widths showed no changes between the 2 treatment groups. Borderline Class I patients treated with extraction of 4 first premolars had decreased maxillary and mandibular intermolar and perimeter measurements compared with nonextraction patients. The maxillary and mandibular intercanine widths showed no significant difference between the 2 treatment groups.


Ground-state degeneracies leave recognizable topological scars in the electronic density.
In Kohn-Sham density functional theory (KS DFT) a fictitious system of noninteracting particles is constructed having the same ground-state (GS) density as the physical system of interest. A fundamental open question in DFT concerns the ability of an exact KS calculation to spot and characterize the GS degeneracies in the physical system. In this Letter we provide theoretical evidence suggesting that the GS density, as a function of position on a 2D manifold of parameters affecting the external potential, is "topologically scarred" in a distinct way by degeneracies. These scars are sufficiently detailed to enable determination of the positions of degeneracies and even the associated Berry phases. We conclude that an exact KS calculation can spot and characterize the degeneracies of the physical system.


Differential cytotoxicity in mouse epidermal JB6 cells: a potential mechanism for oxidant tumor promotion.
It has been suggested that superior antioxidant defense systems protect promotion-sensitive (p+t) mouse epidermal JB6 clone 41 cells from excessive deleterious effects of oxidants, allowing their clonal expansion in contrast to that of promotion-resistant (p-) clone 30 cells. In support of this concept, we report that oxidants produced by xanthine/xanthine oxidase cause more cytotoxicity, cellular damage, and cell death in p-cells. Cell surface blebbing, an early morphological consequence of oxidative injury, was detected in cultures grown on glass coverslips. While a rise in cytosolic ionized calcium ([Ca2+]i) preceding bleb formation was observed in both p+ and p- cells by digital imaging fluorescence microscopy, elevated levels of [Ca2+]i were sustained longer in p- cells. This increase was dependent on the levels of extracellular ionized calcium ([Ca2+]e) in p+ but not p- cells. We conclude that the superior antioxidant defense or improved Ca2+ buffering of promotable clone 41 cells protects them from more severe deregulation of [Ca2+]i and, as a consequence, from excessive cytotoxicity after exposure to oxidant promoters.


Galectin-9 suppresses tumor metastasis by blocking adhesion to endothelium and extracellular matrices.
We previously described an inverse correlation between galectin-9 (Gal-9) expression and metastasis in patients with malignant melanoma and breast cancer. This study verified the ability of Gal-9 to inhibit lung metastasis in experimental mouse models using highly metastatic B16F10 melanoma and Colon26 colon cancer cells. B16F10 cells transfected with a secreted form of Gal-9 lost their metastatic potential. Intravenous Gal-9 administration reduced the number of metastases of both B16F10 and Colon26 cells in the lung, indicating that secreted Gal-9 suppresses metastasis. Analysis of adhesive molecule expression revealed that B16F10 cells highly express CD44, integrin alpha1, alpha 4, alpha V, and beta1, and that Colon26 cells express CD44, integrin alpha2, alpha 5, alpha V, and beta1, suggesting that Gal-9 may inhibit the adhesion of tumor cells to vascular endothelium and the extracellular matrix (ECM) by binding to such adhesive molecules. Indeed, Gal-9 suppressed the binding of hyaluronic acid to CD44 on both B16F10 and Colon26 cells, and also suppressed the binding of vascular cell adhesion molecule-1 to very late antigen-4 on B16F10 cells. Furthermore, Gal-9 inhibited the binding of tumor cells to ECM components, resulting in the suppression of tumor cell migration. The present results suggest that Gal-9 suppresses both attachment and invasion of tumor cells by inhibiting the binding of adhesive molecules on tumor cells to ligands on vascular endothelium and ECM.


Development of a standardized method for contouring the larynx and its substructures.
Limiting radiation dose to the larynx can diminish effects of laryngeal dysfunction. However, no clear guidelines exist for defining the larynx and its substructures consistently on cross-sectional imaging. This study presents computed tomography (CT)- and magnetic resonance imaging (MRI)-based guidelines for contouring laryngeal organs-at-risk (OARs). Standardized guidelines for delineating laryngeal OARs were devised and used to delineate on CT and MRI for head-and-neck cancer patients. Volumetric comparisons were performed to evaluate consistency and reproducibility of guideline-based contours. For the initial 5 patients the mean CT and MRI based larynx volume did not differ significantly between imaging modalities; 34.39 ± 9.85 vs. 35.01 ± 9.47 (p = .09). There was no statistical difference between the CT based mean laryngeal volume in the subsequent 44 patients compared to the initial 5 patients outlined on CT and the MRI scan (p = 0.53 and 0.62). The OAR volume for laryngeal substructures were not statistically different among patients or between imaging modalities. Once established, the guidelines were easy to follow. The guidelines developed provide a precise method for delineating laryngeal OARs. These guidelines need to be validated and clinical significance of outlining laryngeal substructures and dose-volume constraints should be investigated before routine implementation in clinic practice.


Effect of regional and systemic fluorinated pyrimidine chemotherapy on quality of life in colorectal liver metastasis patients.
Since systemic and regional (HAI) fluorinated pyrimidine chemotherapies offer similar survival benefit in treatment of colorectal liver metastases (CLM), we sought to identify their impact on quality of life (QoL), which might be a useful indicator of treatment preference. We compared QoL in 135 CLM patients managed by symptom control (n = 49 patients), systemic fluorouracil (5FU)/folinic acid (n = 35), or hepatic arterial floxuridine (FUDR) (n = 51). Full blood count and liver function tests, World Health Organization (WHO) toxicity criteria, and QoL (Rotterdam Symptom Checklist [RSC], the Sickness Impact Profile [SIP], and the Hospital Anxiety and Depression scale [HAD]) were measured monthly in all patients. The HAD anxiety score was significantly increased in symptom control compared with chemotherapy patients 1 month after randomization. There was a significant increase in RSC physical score (repeated measures, P = .05), and in scores for sore mouth (P < .01), dry mouth (P < .01), and tingling hands and feet (P < .01) in systemic chemotherapy compared with symptom control patients. Significant QoL differences (repeated measures and Mann-Whitney U [MWU]) between HAI and symptom control patients were not detected. Systemic chemotherapy patients lived for significantly longer (log-rank test, P < or = .0001) with abnormal HAD anxiety, RSC psychosocial, or RSC sore mouth scores compared with HAI patients, but there were no overall survival differences. Randomization to symptom control only was associated with increased anxiety. QoL with systemic chemotherapy was impaired by side effects. HAI was associated with similar survival to systemic chemotherapy but with better sustained QoL.


Evaluation of pre- and post-surgical oxidative stress parameters in patients with pulmonary cystic echinococcus.
Hydatid cyst secretes numerous immunomodulatory molecules to the host, and the host reacts these molecules by activating immune response. It is also known that, immune cells generally produce more oxidative products. In this study, we aimed to evaluate the antioxidant enzyme using catalase (CAT) and oxidant enzyme using lipid hydroperoxide (LOOH) levels in the serum samples before and after the surgical interventions in patients with pulmonary cystic echinococcus (CE). Forty patients with pulmonary CE who underwent surgery and 40 healthy individuals were enrolled to the study. Patients were divided in two groups; group 1 (n=40) consisted of patients with pulmonary CE, and group 2 (n=40) consisted of healthy subjects. Before and after surgical interventions serum CAT and LOOH levels were measured. Compared to group 2, group 1 had significantly lower CAT and higher LOOH levels before surgery (both p < 0.001). In group 1; CAT levels were significantly increased and LOOH levels significantly increased after the surgical intervention (both p < 0.001). The present study showed that oxidative stress increased in patients with pulmonary CE, may be consequence of immune response of the host, and these levels decreased after the surgical intervention.


Parasitic small-moment antiferromagnetism and nonlinear coupling of hidden order and antiferromagnetism in URu2Si2 observed by Larmor diffraction.
We report for the first time simultaneous microscopic measurements of the lattice constants, the distribution of the lattice constants, and the antiferromagnetic moment in high-purity URu(2)Si(2), combining Larmor and conventional neutron diffraction at low temperatures and pressures up to 18 kbar. Our data demonstrate quantitatively that the small moment in the hidden order (HO) of URu(2)Si(2) is purely parasitic. The excellent experimental conditions we achieve allow us to resolve that the transition line between HO and large-moment antiferromagnetism (LMAF), which stabilizes under pressure, is intrinsically first order and ends in a bicritical point. Therefore, the HO and LMAF must have different symmetry, which supports exotic scenarios of the HO such as orbital currents, helicity order, or multipolar order.


Outdoor Cultivation of Marine Diatoms for Year-Round Production of Biofuels.
Biofuel production using microalgae is believed to have the advantage of continuous year-round production over crop plants, which have strong seasonality. However, actual year-round production of microalgal lipids using outdoor mass cultivation has rarely been demonstrated. In our previous study, it was demonstrated that the oleaginous diatom, Fistulifera solaris, was culturable in outdoor bioreactors from spring to autumn, whereas biomass and lipid production in winter failed because F. solaris did not grow below 15 °C. Therefore, another candidate strain that is culturable in winter is required. In this study, a cold-tolerant diatom, Mayamaea sp. JPCC CTDA0820, was selected as a promising candidate for biofuel production in winter. Laboratory-scale characterization revealed that this diatom was culturable at temperatures as low as 10 °C. Subsequently, F. solaris (April-October) and Mayamaea sp. JPCC CTDA0820 (November-March) were cultured in outdoor open-pond bioreactors, wherein year-round production of diatom lipids was successfully demonstrated. The maximal values of areal productivities of biomass and lipids reached to 9.79 and 1.80 g/(m² day) for F. solaris, and 8.62 and 0.92 g/(m² day) for Mayamaea sp. JPCC CTDA0820, respectively. With the combined use of these two diatom species, stable year-round production of microalgal lipids became possible.


Algoriphagus roseus sp. nov., isolated from a hexachlorocyclohexane-contaminated dumpsite.
A Gram-staining negative, reddish-pink, non-motile, rod-shaped bacterial strain designated W29T, was isolated from a hexachlorocyclohexane-contaminated dumpsite located in the northern part of India at Ummari Village, Lucknow. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain W29T formed a lineage within the genus Algoriphagusand exhibited highest sequence similarity to Algoriphagus trabzonensis MS7T (98.8 %), followed by Algoriphagusalkaliphilus AC-74T (97.1 %). The 16S rRNA gene sequence similarity between strain W29T and other species of the genus Algoriphagusranged from 93.3-98.8 %. The DNA-DNA relatedness between strain W29T and A. trabzonensisMS7T was 47 % and with other related strains was found to be less than 45 %, confirming strain W29T represents a novel species. The DNA G+C content of strain W29T was 46.2 mol%. Strain W29T was oxidase- and catalase-positive. The major fatty acids (>10 %) of strain W29T were iso-C15 : 0, summed feature 9 (comprising 10-methyl C16 : 0 and/or iso-C17 : 1ω9c) and summed feature 3 (comprising C16 : 1ω6c and/or C16 : 1ω7c). The respiratory quinone was MK-7. The polar lipid profile consisted of phosphatidylethanolamine, diphosphatidylglycerol, two unidentified aminolipids, an unidentified aminophospholipid, an unidentified phospholipid and unidentified lipids. On the basis of the results obtained from DNA-DNA hybridization, and biochemical and physiological tests in this study, strain W29T represents a novel species of the genus Algoriphagus for which the name Algoriphagus roseus sp. nov. is proposed. The type strain is W29T (=KCTC 42940T=MCC 2876T=DSM 100160T).


[Treatment of DIC associated with hematological malignancies].
To improve the prognosis of patients with hematological malignancies, close attention should be paid to major hemorrhage in the clinical management of patients with disseminated intravascular coagulation (DIC) associated with hematological malignancies, especially from diagnosis to induction therapy. Cerebral, alveolar, and GI tract hemorrhages may cause a life-threatening event. Therefore, DIC should always be suspected, and careful observation for hemorrhage and hemostatic examination should be performed. The diagnostic criteria for DIC according to the Japanese Ministry of Health and Welfare and the Japanese Society on Thrombosis and Hemostasis (2017) are useful resources for the diagnosis of DIC associated with hematological malignancies. Following diagnosis, treatment for DIC should be initiated as soon as possible, and the risk of hemorrhage should be considered when choosing the anticoagulant. Sufficient amount of fresh frozen plasma or platelet concentrates should be used if necessary. Recombinant human soluble thrombomodulin has promising potential for use as a drug for the treatment of DIC associated with hematological malignancies that can manage a wide range of pathologic processes such as hypercoagulable states, inflammation, excessive fibrinolysis, and easy hemorrhage caused by endothelial cell damage.


The ginseng pimple: an inflammatory papule following ginseng consumption.
Ginseng is a popular herbal remedy derived from the plant roots of the Panax genus and has been used in traditional Asian medicine for thousands of years. In the United States, it has become increasingly popular and is taken for many conditions, including as an immune enhancer. Cutaneous adverse effects have been reported to occur following ginseng consumption, although detailed clinical descriptions are limited. A 60-year-old woman who repeatedly developed inflammatory papules following ginseng consumption is described and the characteristics of ginseng use in healthcare are reviewed.


[Neuroimaging and clinical manifestations of herpes simplex encephalitis in children].
Mortality rates in herpes simplex encephalitis are still high because the condition is diagnosed too late and so specific treatment is delayed. We present a retrospective study of patients with herpes encephalitis. If in a pediatric patient with CNS infection MR images show high intensity signal lesions in characteristic localization, herpes etiology should be taken into consideration, so as to undertake appropriate treatment possibly early.


Acetone as an anticonvulsant.
Recent interest in the anticonvulsant effects of acetone has stemmed from studies related to the ketogenic diet (KD). The KD, a high-fat diet used to treat drug-resistant seizures, raises blood and brain levels of three ketones: beta-hydroxybutyrate, acetoacetate, and acetone. An obvious question is whether these ketones have anticonvulsant properties. We found that neither beta-hydroxybutyrate nor acetoacetate has proven to be anticonvulsant. Acetone, however, is clearly anticonvulsant at physiological, and near-physiological, nontoxic concentrations. Despite knowledge of acetone's anticonvulsant properties since the 1930's, acetone had never been characterized using the standard animal seizure tests. In our recent experiments, acetone was found to be active in animal models of tonic-clonic seizures, typical absence seizures, complex partial seizures, and atypical absence seizures associated with Lennox-Gastaut syndrome. Therapeutic indices are either comparable or better than that of valproate, a standard broad-spectrum anticonvulsant. A number of acetone-like molecules have also been tested, and these also show good potency up to a "cutoff" point of nine carbons contained in the side chain. Above this number, potency disappears, suggesting the possibility of a receptor for acetone and its analogs.


The new cassane-type diterpenes from Caesalpinia minax.
Four new cassane-type diterpenes, Neocaesalpin S (1), Neocaesalpin T (2), Neocaesalpin U (3), and Neocaesalpin V (4) were isolated from Caesalpinia minax HANCE together with seven known compounds Neocaesalpin A (5), Neocaesalpin K (6), Neocaesalpin L (7), Neocaesalpin M (8), Neocaesalpin O (9), Neocaesalpin MP (10), and Magnicaesalpin (11). Their structures were elucidated on the basis of 1D- and 2D-NMR, MS, and circular dichroism (CD) analysis. Compounds 1-4 were tested against liver cancer (HepG-2) and breast cancer (MCF-7), and showed mild antiproliferative activity.


Multiple intracranial meningiomas associated with intracranial arterial aneurysm.
This report illustrates a patient who was found to harbor eight separate meningiomas associated with an intracranial arterial aneurysm. Five of the meningiomas were extirpated and the aneurysm was wrapped. The causality between multiple meningiomas and aneurysm is obscure. Although the introduction of CT has facilitated the diagnosis of multiple meningiomas there are however areas especially in the base of the skull and high parasagittally where small meningiomas may remain undetected.


Area of the diabetic ulcers estimated applying a foot scanner-based home telecare system and three reference methods.
Diabetic foot ulcer area is a basic parameter used for monitoring the wound healing and effectiveness of the treatment applied. TeleDiaFoS (developed earlier in collaboration with the Department and Clinic of Gastroenterology and Metabolic Diseases, Medical University of Warsaw, Warsaw, Poland) is one of just a few systems available that make possible monitoring of the wound size remotely based on the foot scans transmitted to the physician from a patient's home. The aim of this study was to compare the diabetic foot ulcer areas measured using TeleDiaFoS with the results obtained using three reference methods. The reference measurements were conducted using the elliptical method with a ruler, the wound tracing method and planimetrics with the Visitrak (Smith & Nephew, London, UK) system, and the pattern-coded structured light method with the Silhouette (ARANZ Medical, Christchurch, New Zealand) system. Regression and Bland-Altman analyses were performed. The study group consisted of 23 diabetes patients with plantar foot ulcers. Thirty-three wounds were successfully examined. The measurement method influenced the measured area significantly (P=0.00005). The correlation coefficients between TeleDiaFoS and the ruler, Visitrak, and Silhouette methods were 0.949, 0.985, and 0.987, and the limits of agreement equaled -1.3±5.5 cm(2), -0.4±2.2 cm(2), and -0.6±2.1 cm(2), respectively. The strong linear relationships obtained can be used to convert the wound area measured with TeleDiaFoS to the corresponding value of each of the reference methods. The results indicate that the wound area of plantar ulcers in diabetes might be monitored effectively using the TeleDiaFoS system based on the foot scans that the patient can produce at home with no assistance of other persons.


Genotype-phenotype analysis of selective failure of tooth eruption-A systematic review.
Tooth eruption is an important and unique biological process during craniofacial development. Both the genetic and environmental factors can interfere with this process. Here we aimed to find the failure pattern of tooth eruption among five genetic diseases. Both systematic review and meta-analysis were used to identify the genotype-phenotype associations of unerupted teeth. The meta-analysis was based on the characteristics of abnormal tooth eruption in 223 patients with the mutations in PTH1R, RUNX2, COL1A1/2, CLCN7, and FAM20A respectively. We found all the patients presented selective failure of tooth eruption (SFTE). Primary failure of eruption patients with PTH1R mutations showed primary or isolated SFTE1 in the first and second molars (59.3% and 52% respectively). RUNX2 related cleidocranial dysplasia usually had SFTE2 in canines and premolars, while COL1A1/2 related osteogenesis imperfecta mostly caused SFTE3 in the maxillary second molars (22.9%). In CLCN7 related osteopetrosis, the second molars and mandibular first molars were the most affected. While FAM20A related enamel renal syndrome most caused SFTE5 in the second molars (86.2%) and maxillary canines. In conclusion, the SFTE was the common characteristics of most genetic diseases with abnormal isolated or syndromic tooth eruption. The selective pattern of unerupted teeth was gene-dependent. Here we recommend SFTE to classify those genetic unerupted teeth and guide for precise molecular diagnosis and treatment.


Autoradiographic localization of 8-methoxypsoralen in psoriasis skin in vitro.
Slices of psoriatic (Pso) skin were incubated with tritiated 8-methoxypsoralen (8-MOP) and exposed to UVA irradiation. The photobinding of 8-MOP was studied by autoradiography at the cellular level and in the different layers of the epidermis and in the dermis. Silver grains were found in the nucleus and the cytoplasm of the various cell types. Keratin, collagen and lipoproteins were also labelled. The upper malpighian cells and the parakeratotic cells showed a greater degree of labelling than did the basal layers. In skin incubated with [3H]8-MOP and unirradiated, no measurable labelling was detected. These results suggest that the targets responsible for the therapeutic activity of 8-MOP might be not only nucleic acids, but also proteins.


Concomitant induction of apoptosis and necrosis in cerebellar granule cells following serum and potassium withdrawal.
Serum and potassium withdrawal-induced cell death of cerebellar granule cells is one of the most popular models used for studying neuronal apoptosis in vitro, and it is generally assumed that compounds preventing cell death in this model prevent apoptosis. In the present study we demonstrate that serum and potassium withdrawal induces a mixture of apoptosis and necrosis rather than apoptosis only. Each of these death mechanisms could be blocked by activation of different pathways, such as raising cAMP production or stimulation of the IGF-1 receptor. Studies on serum and potassium withdrawal-induced cell death of cerebellar granule cells should therefore carefully assess whether a given compound is preventing apoptosis or necrosis using appropriate techniques.