Novel defect structures in a strongly confined liquid-crystalline blue phase.
In our numerical study based on a phenomenological description of strongly confined liquid crystalline blue phase I (BP I), we find several novel structures characterized by specific configurations of topological disclination lines. The thickness of the system is of the order of the dimension of the unit cell of the bulk BP I, and the confining surfaces adopts homeotropic anchoring. The structures include an array of double-helix disclination lines accompanied by an orthorhombic lattice of double-twist cylinders, and two parallel arrays of winding disclination lines almost perpendicular to each other.


Fluorescence quenching studies of nitrated polycyclic aromatic hydrocarbons.
The analysis of nitrated polycyclic aromatic hydrocarbons (NPAHs) is of great importance because of the mutagenicity and possible carcinogenic activity of these compounds, which are distributed widely in the environment. Nitro-substituents in aromatic compounds are known to quench fluorescence and NPAHs have no intrinsic fluorescence, but they can be determined using their quenching effects on other fluorophores. The quenching effects of several important NPAHs on 1,2,3,4- tetrahydro-1-naphthol,5,6,7,8-tetrahydro-1-naphthol,4-(2-hydroxy-4-sulfo-1-naphthylazo)-2-naphthalene carboxylic acid and 7-amino-4-methyl coumarin have been studied. The singlet emission of these fluorophores is efficiently quenched by all the NPAHs, the quenching following the Stern-Volmer relationship. Quenching constants and the limits of detection and linear ranges of the quenchers have been determined in each case: the limits of detection are ca 1 µm.


Effect of Parental Adverse Childhood Experiences on Intergenerational DNA Methylation Signatures.
Adverse Childhood Experiences (ACEs) are events that occur before a child turns 18 years old that may cause trauma. In this study, the effect of cumulative ACEs experienced on human maternal DNA methylation (DNAm) was estimated while accounting for interaction with domains of ACEs in prenatal peripheral blood mononuclear cell samples from the Maternal and Developmental Risks from Environmental Stressors (MADRES) pregnancy cohort. The intergenerational transmission of ACE-associated DNAm was also explored used paired maternal and neonatal cord blood samples. Replication in buccal samples was explored in the Children's Health Study (CHS). We used a four-level categorical indicator variable for ACEs exposure: none (0 ACEs), low (1-3 ACEs), moderate (4-6 ACEs), and high (> 6 ACEs). Effects of ACEs on maternal DNAm (N = 240) were estimated using linear models. To evaluate evidence for intergenerational transmission, mediation analysis was used. Analysis of maternal samples displayed some shared but mostly distinct effects of ACEs on DNAm across low, moderate, and high ACEs categories. CLCN7 and PTPRN2 was associated with maternal DNAm in the low ACE group and this association replicated in the CHS. ACE-associated methylation was observed in maternal and neonatal profiles in the COMT promoter region, with some evidence of mediation by maternal COMT methylation. Specific genomic loci exhibited mutually exclusive maternal ACE effects on DNAm in either maternal or neonatal population. There is some evidence for an intergenerational effect of ACEs, supported by shared DNAm signatures in the COMT gene across maternal-neonatal paired samples.


[Effect of Bacillus pumilus ribonuclease on the paramagnetic centers of microbial cells].
Potential clinical application of Bacillus pumulus cytotoxic ribonuclease (binase) selectively inducing the death of tumor cells makes it imperative to investigate its effect on the normal human microflora. Flow cytometry was used to determine that binase concentration causing the apoptosis of cancer cells had no effect of the viability of Escherichia coli K12. The changes in the paramagnetic centers of E. coli K12 cells in the presence of nontoxic binase concentrations revealed by EPR spectroscopy included higher EPR signals from iron-containing proteins (including those from the Fe-S clusters) and of the Mn(II) hyperfine structure. The TMTH spin probe (N-(1-hydroxy-2,2,6,6-tetramethylpiperidine-4-il)-2-methylpropanamide hydrochloride) was used to reveal a twofold increase in the levels of reactive oxygen species (ROS) in the cells, which induced oxidative stress in the enzyme-treated bacteria. Inductively coupled plasma mass spectrometry revealed elevated contents of alkaline (Li, Na, K), alkali earth (Mg, Ca), transition (Cr, Mn, Fe, Cu, Zn), and post-transition metals (Bi, Pb) in the cells. Elevated levels of Cu and Zn (which impair the activity of the respiratory chain enzymes) and of Mn, which is known as a superoxide dismutase cofactor, confirmed development of the oxidative stress in bacteria.


The Evolution of Disaster Risk Management: Historical Approach.
The concept of Disaster Risk Management (DRM) has changed throughout history. Identifying changes and related factors can be effective in adopting logical, scientific and evidence-based approaches in the future. Therefore, this study was conducted with the aim of depicting the process of changes in the concept of DRM and creating an original perspective. In this narrative literature review study, we used historical approach. Literature, regardless of the time of publication, was searched using divergent keywords including "disaster, health, emergency, management, risk, disaster medicine, and hazard." DRM evolution started with the emergence of civil defense during the last century. Although DRM was initially focused on responses, currently, this concept includes disaster risk reduction (DRR) and disaster management. DRR includes prevention and mitigation, and disaster management includes response and recovery measures. DRR considering underlying risk factors such as social factors, and focusing on participation of communities are important steps to be taken.


[Hutchinson-Horton giant cell arteritis and rhizomelic polymyalgia. II. Rhizomelic polymyalgia. Arteritic polymyalgia].
Rhizomelic polymyalgia is an inflammatory form. Its site of choice is the shoulder girdle and it is almost solely observed in elderly subjects. An account is given of its epidemiological, clinical and anatomopathological aspects. Its aetiology is also discussed with particular reference to its possible immunological or vascular origin. The rheumatic symptoms of rhizomelic polymyalgia are similar to those observed in temporal arteritis. Since artery lesions are found in most cases, the name "polymyalgia arteritica" has been suggested as an alternative clinical description by Hamrin .


Spectrographic comparison of two types of spastic dysphonia.
A spectrographic comparison of the voices of two patients with spastic dysphonia demonstrated differences in vocal characteristics. The voice of one patient was characterized by intermittent breathiness which appeared spectrographically as a breakdown in formant structure or as the addition of fricative fill superimposed upon resonance bars. The voice of the second patient was characterized by strain-strangle phonation which appeared spectrographically as widely and irregularly spaced vertical striations. The contrasting vocal characteristics of the two patients are compatible with the viewpoint that there may be two types of spastic dysphonia.


CYP4F22-Related Autosomal Recessive Congenital Ichthyosis: Clinical Presentation.
Autosomal recessive congenital ichthyosis (ARCI) is a group of hereditary, nonsyndromic disorders of keratinization. ARCI encompasses several different clinical presentations and is caused by various genetic mutations. Commonly, ARCI presents with a taut, thick, shiny stratum corneum called a collodion membrane, but patients with mutations in CYP4F22 frequently present only with erythroderma. We report the case of a patient who was heterozygous for a pathogenic variant and a variant of uncertain significance in the CYP4F22 gene and presented with a collodion membrane and developed a mild ichthyosis phenotype.


Soy Infant Formula may be Associated with Autistic Behaviors.
The effects of soy-based infant formulas on childhood development are not well understood. This exploratory study evaluates the severity of autistic behaviors in association with the use of soy-based infant formula in a population of high-functioning autistic children. Medical record data were analyzed from the Simons Foundation Autism Research Initiative Simplex Collection, which included data on infant formula use and autism diagnostic scores for 1,949 autistic children. We found exploratory associations between the use of soy-based infant formula and several autistic behaviors as assessed by line-item analysis of the Aberrant Behavior Checklist, Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. This study provides preliminary data that the use of soy-based infant formula may be associated with specific autistic behaviors.


Analysis of Classes Used in the Treatment of Depression by Physician-reported Severity.
We analyzed use of therapeutic drug classes for the treatment of depression by the three levels of physician-reported disease severity (mild, moderate, and severe) to understand if the mix of therapeutic classes used to treat depression changes as disease severity increases. Prior to analyzing drug uses in each severity category, we established that in the 12 months ending November 2009, the majority of patients (65%) were assigned a severity rating of 'moderate' by their physician; 27 percent and eight percent of patients were designated as 'mild' and 'severe,' respectively. In general, we found that as disease severity changes, so too do the proportions of the various therapeutic classes used in depression. The differences in class mix by severity have persisted at least since the 12 months ending December 2008, and it appears that the mix of drug classes used in severe depression are becoming less similar to the class mix for moderate depression over time.


Vascular hand-arm vibration syndrome--magnetic resonance angiography.
The diagnosis of vascular hand-arm vibration syndrome (HAVS) requires consistent symptoms, photographic evidence of digital blanching and sufficient exposure to hand-transmitted vibration (HTV; A(8) > 2.5 m/s2). There is no reliable quantitative investigation for distinguishing HAVS from other causes of Raynaud's phenomenon and from normal individuals. Hypothenar and thenar hammer syndromes produce similar symptoms to HAVS but are difficult to diagnose clinically and may be confused with HAVS. Magnetic resonance angiography (MRA) is a safe and minimally invasive method of visualizing blood vessels. Three cases of vascular HAVS are described in which MRA revealed occlusions of the ulnar, radial and superficial palmar arteries. It is proposed that HTV was the cause of these occlusions, rather than blows to the hand unrelated to vibration, the assumed mechanism for the hammer syndromes. All three cases were advised not to expose their hands to HTV despite one of them being at Stockholm vascular stage 2 (early). MRA should be the investigation of choice for stage 2 vascular HAVS or vascular HAVS with unusual features or for a suspected hammer syndrome. The technique is however technically challenging and best done in specialist centres in collaboration with an occupational physician familiar with the examination of HAVS cases. Staging for HAVS should be developed to include anatomical arterial abnormalities as well as symptoms and signs of blanching. Workers with only one artery supplying a hand, or with only one palmar arch, may be at increased risk of progression and therefore should not be exposed to HTV irrespective of their Stockholm stage.


Naphtho[2,3-a]pyrene forms chiral domains on Au111.
Chiral domains have been prepared by evaporation of a two-dimensionally chiral molecule, naphtho[2,3-a]pyrene (NP), onto the hexagonal Au(111) surface in an ultrahigh vacuum environment. High-resolution UHV scanning tunneling microscopy (STM) showed that NP formed chiral domains consisting of only one 2D enantiomer rather than racemic two-dimensional unit cells. A structural model is proposed that agrees with the STM observations. Chiral pockets between adsorbed molecules may be useful for binding a specific enantiomer of a 3D chiral molecule.


Cloning and characterization of the platypus mitochondrial genome.
The vertebrate mitochondrial genome is highly conserved in size and gene content. Among the chordates there appears to be one basic gene arrangement, but rearrangements in the mitochondrial gene order of the avian lineages have indicated that the mitochondrial genome may be more variable than once thought. Different gene orders in marsupials and eutherian mammals leave the ancestral mammalian order in some doubt. We have investigated the mitochondrial gene order in the platypus (Ornithorhynchus anatinus), a representative of the third major group of mammals, to determine which mitochondrial gene arrangement is ancestral in mammals. We have found that the platypus mtDNA conforms to the basic chordate gene arrangement, common to fish, amphibians, and eutherian mammals, indicating that this arrangement was the original mammalian arrangement, and that the unusual rearrangements observed in the avians and marsupials are probably lineage-specific.


[Epidemiologic study of bluetongue in sheep, cattle and different species of wild animals in the Ivory Coast].
Between 1992 and 1993, a serological survey was conducted in Côte d'Ivoire on 623 sera from sheep, 215 sera from cattle and 211 sera from wild herbivores. These sera were tested for bluetongue virus (BTV) antibodies using an agar gel immunodiffusion test. The purpose of this survey was twofold: to establish the incidence of bluetongue in the country, and to analyse the putative role of BTV in the reproductive pathology of sheep. Seroprevalence was 52 +/- 4% in sheep, 95 +/- 3% in cattle, and 56 +/- 7% in wild herbivores. The authors found antibodies against BTV in kob (Kobus kob Erxleben, 1777), common waterbuck (Kobus ellipsiprymnus Ogilby, 1833), roan antelope (Hippotragus equinus Desmarest, 1804), buffalo (Syncerus caffer Sparrman, 1779), hartebeest (Alcelaphus buselaphus Pallas, 1766) and elephant (Loxodonta africana Blumenbach, 1797). A significant difference was found in seroprevalence in sheep between the three areas covered by the survey. Antibody prevalence increased significantly with age in sheep and wild herbivores, and seroprevalence was higher in dams with a history of abortion. It can therefore be concluded that bluetongue is enzootic in Côte d'Ivoire.


Functional amblyopia associated with abnormalities of the optic nerve.
Seven patients with structural abnormalities of one or both of their optic nerves had decreased visual acuity partly due to functional amblyopia. They were treated with conventional amblyopia therapy and their visual acuities improved. Functional amblyopia can coexist either secondary to, or coincidentally with, structural optic nerve abnormalities.


Sympathomimetic decongestants during pregnancy: risks for the unborn child.
In addition to the risk of cardiovascular events and neurological disorders, sympathomimetic decongestants have teratogenic potential, albeit weak, when taken during the first trimester of pregnancy, probably through disruption of the vascular system of the embryo and the pregnant woman. In the second and third trimesters of pregnancy, the fetus is exposed to the same adverse effects as the mother.


Charge Transport in MoS2/WSe2 van der Waals Heterostructure with Tunable Inversion Layer.
Despite numerous studies on two-dimensional van der Waals heterostructures, a full understanding of the charge transport and photoinduced current mechanisms in these structures, in particular, associated with charge depletion/inversion layers at the interface remains elusive. Here, we investigate transport properties of a prototype multilayer MoS2/WSe2 heterojunction via a tunable charge inversion/depletion layer. A charge inversion layer was constructed at the surface of WSe2 due to its relatively low doping concentration compared to that of MoS2, which can be tuned by the back-gate bias. The depletion region was limited within a few nanometers in the MoS2 side, while charges are fully depleted on the whole WSe2 side, which are determined by Raman spectroscopy and transport measurements. Charge transport through the heterojunction was influenced by the presence of the inversion layer and involves two regimes of tunneling and recombination. Furthermore, photocurrent measurements clearly revealed recombination and space-charge-limited behaviors, similar to those of the heterostructures built from organic semiconductors. This contributes to research of various other types of heterostructures and can be further applied for electronic and optoelectronic devices.


Development of a Model to Predict the Primary Infection Date of Bacterial Spot (Xanthomonas campestris pv. vesicatoria) on Hot Pepper.
A population model of bacterial spot caused by Xanthomonas campestris pv. vesicatoria on hot pepper was developed to predict the primary disease infection date. The model estimated the pathogen population on the surface and within the leaf of the host based on the wetness period and temperature. For successful infection, at least 5,000 cells/ml of the bacterial population were required. Also, wind and rain were necessary according to regression analyses of the monitored data. Bacterial spot on the model is initiated when the pathogen population exceeds 10(15) cells/g within the leaf. The developed model was validated using 94 assessed samples from 2000 to 2007 obtained from monitored fields. Based on the validation study, the predicted initial infection dates varied based on the year rather than the location. Differences in initial infection dates between the model predictions and the monitored data in the field were minimal. For example, predicted infection dates for 7 locations were within the same month as the actual infection dates, 11 locations were within 1 month of the actual infection, and only 3 locations were more than 2 months apart from the actual infection. The predicted infection dates were mapped from 2009 to 2012; 2011 was the most severe year. Although the model was not sensitive enough to predict disease severity of less than 0.1% in the field, our model predicted bacterial spot severity of 1% or more. Therefore, this model can be applied in the field to determine when bacterial spot control is required.


Anomalous Hall conductivity in a honeycomb topological insulator under counter-rotating bicircular laser field.
We investigate the interaction between the counter-rotating bicircular field and the trivial and topological insulator with anomalous Hall conductivity (AHC) to show the effect of the asymmetric spin band and topological invariant. We show that the reaction of the system to the counter-rotating bicircular field is classified into the high-field and low-field regimes. In the high-field regime, it is shown that the AHC of the system is controlled by the phase difference between the ω0 and 2ω0 fields. We also show that in the low-field regime, the AHC of the topological insulator is determined by the helicity of the laser, while the AHC is negligible in the trivial insulator. For the spin-orbit coupling (SOC), it is demonstrated that the high SOC increases the required field amplitude for the transition from the low-field to the high-field regime. Also, we show that strong SOC leads to an additional sign change of the AHC in the high-field regime, but with different origins in the trivial and topological insulator.


Advanced titration to treat a floppy epiglottis in selective upper airway stimulation.
The following report presents a case of a patient with high residual apnea-hypopnea index at 6 months following implantation of an upper airway stimulation device who improved significantly after advanced titration via drug-induced sedated endoscopy by changing the electrode configuration for stimulation from bipolar to monopolar. This case demonstrates the utility of postsurgical advanced titration to optimize programming settings for improved clinical outcomes. Laryngoscope, 126:S22-S24, 2016.


Predicting incident diabetes in Jamaica: the role of anthropometry.
To evaluate the performance of the body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHTR) in predicting incident diabetes in Jamaica. A cohort of 728 nondiabetic adults (290 men and 438 women), ages 25 to 74 years and residents of Spanish Town, Jamaica, were followed for a mean of 4 years. Participants had fasting and 2-hour postchallenge glucose concentrations measured at baseline and follow-up. There were 51 cases of incident diabetes (17 men and 34 women). All indices were independent predictors of diabetes, and none was clearly superior. The area under the receiver operating characteristics curves (95% confidence interval) for BMI was 0.74 (0.59 to 0.88) for men and 0.62 (0.51 to 0.72) for women. For waist circumference, these values were 0.78 (0.65 to 0.91) in men and 0.61 (0.50 to 0.71) in women. Similar results were obtained for WHR and WHTR. "Optimal" cut-off points for BMI were 24.8 kg/m(2) (men) and 29.3 kg/m(2) (women). For waist circumference, these were 88 cm and 84.5 cm for men and women, respectively. Corresponding values for WHR were 0.87 and 0.80 and for WHTR were 0.51 and 0.54, respectively. Cut-off points for waist circumference and WHR were similar to those proposed in developed countries for women but lower in men. Waist circumference could be useful in health promotion as an alternative to BMI.


Is reduction mammaplasty a stimulus for weight loss and improved quality of life?
Reducing breast size for women with macromastia does more than provide symptomatic relief. The purpose of this study was to evaluate whether reduction mammaplasty was felt to be a stimulus for postoperative weight loss, subjective glucose control, and improved self-confidence. All patients who underwent reduction mammaplasty at Emory University Hospital by the senior author were reviewed. Patient demographics were queried, and a standardized questionnaire was devised to obtain information regarding postoperative weight, dress size, glucose control, and exercise. Forty-one women participated in the questionnaire. Mean follow-up was 2 years (range, 1-6). Patients were stratified according to whether they felt reduction mammaplasty was a stimulus for future weight loss; 63% stated yes (group A), 37% responded no (group B). Group A had significant postoperative weight loss (P < 0.001) and decreased dress size (P < 0.001). Group B had no change in weight (P = 0.239) or dress size (P = 0.735). There was 100% improvement of patient reported postoperative glucose control in group A and 50% improvement in group B. Sexual activity was improved in 85% of women in group A, and only 40% in group B. Group A patients had significantly increased postoperative exercise (P < 0.001); group B had no change. Reduction mammaplasty in motivated patients may be a stimulus for postoperative weight loss, and those patients were more physically active, had better glucose control and had an improved self-confidence.


Anaerobic oxidation of short-chain hydrocarbons by marine sulphate-reducing bacteria.
The short-chain hydrocarbons ethane, propane and butane are constituents of natural gas. They are usually assumed to be of thermochemical origin, but biological formation of ethane and propane has been also observed. Microbial utilization of short-chain hydrocarbons has been shown in some aerobic species but not in anaerobic species of bacteria. On the other hand, anaerobic utilization of short-chain hydrocarbons would in principle be expected because various anaerobic bacteria grow with higher homologues (> or =C(6)). Indeed, chemical analyses of hydrocarbon-rich habitats with limited or no access of oxygen indicated in situ biodegradation of short-chain hydrocarbons. Here we report the enrichment of sulphate-reducing bacteria (SRB) with such capacity from marine hydrocarbon seep areas. Propane or n-butane as the sole growth substrate led to sediment-free sulphate-reducing enrichment cultures growing at 12, 28 or 60 degrees C. With ethane, a slower enrichment with residual sediment was obtained at 12 degrees C. Isolation experiments resulted in a mesophilic pure culture (strain BuS5) that used only propane and n-butane (methane, isobutane, alcohols or carboxylic acids did not support growth). Complete hydrocarbon oxidation to CO2 and the preferential oxidation of 12C-enriched alkanes were observed with strain BuS5 and other cultures. Metabolites of propane included iso- and n-propylsuccinate, indicating a subterminal as well as an unprecedented terminal alkane activation with involvement of fumarate. According to 16S ribosomal RNA analyses, strain BuS5 affiliates with Desulfosarcina/Desulfococcus, a cluster of widespread marine SRB. An enrichment culture with propane growing at 60 degrees C was dominated by Desulfotomaculum-like SRB. Our results suggest that diverse SRB are able to thrive in seep areas and gas reservoirs on propane and butane, thus altering the gas composition and contributing to sulphide production.


Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands.
Objective. This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM). Materials and Methods. Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal protein adduct (4-HNE), oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA), 8-isoprostanes (8-isoP), and oxidative stress index (OSI) were measured at 7 (groups 1 and 3) and 14 (groups 2 and 4) days of experiment. Results. The unstimulated salivary flow in DM rats was reduced in the 2nd week, while the stimulated flow was decreased throughout the duration of the experiment versus control. OSI was elevated in both diabetic glands in the 1st and 2nd week, whereas 8-isoP and 8-OHdG were higher only in the parotid gland in the second week. PC and 4-HNE were increased in the 1st and 2nd week, whereas oxy-LDL/MDA was increased in the 2nd week in the diabetic parotid glands. Conclusions. Diabetes induces oxidative damage of the salivary glands, which seems to be caused by processes taking place in the salivary glands, independently of general oxidative stress. The parotid glands are more vulnerable to oxidative damage in these conditions.


[Effect of benzene exposure on hematology and hepatic drug metabolic enzymes in ethanol administrated rats].
There are few reports regarding the effects of benzene and ethanol being administered simultaneously. In our experiments with 4 groups (controls, ethanol, benzene and ethanol plus benzene) Wistar male rats were treated with ethanol (20%) for 5 weeks, and then exposed to benzene (0.26 g/kg) for 5 days per week for 3 weeks. We also investigated the effects of benzene on the body weight, organ weight, peripheral hematology and hepatic drug metabolizing enzymes in the ethanol administrated rats. The liver weight increased significantly, but spleen weight decreased significantly in the benzene exposed group. Hematological examination showed a decrease of leukocyte in the two groups of benzene and ethanol plus benzene in comparison with the controls, but an effect promoted by ethanol was not found. Serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) values were not significantly different in the exposure groups when compared with the controls. The contents of microsomal cytochrome P450 in all the exposed groups showed a tendency to increase, but they were not significantly different in comparison with the controls. On the other hand, hepatic glutathione S-transferase activity in the exposed groups increased significantly.


A suspected case of ornithine transcarbamylase deficiency in a cat.
An 18 month-old, intact female American Shorthair cat was presented for evaluation of stunted growth and postprandial depression. Fasting serum ammonia and serum bile acid concentrations were above reference ranges at 396 microg/dl and 6.5 micromol/ l and their postprandial concentrations were 785 microg/dl and 9.5 micromol/l, respectively. The initial tentative diagnosis of a portosystemic shunt was excluded by mesenteric portography and histopathology of the liver. The cat was then suspected of a urea cycle enzyme deficiency and its urine was analyzed by gas chromatography-mass spectrometry. A presumptive diagnosis of ornithine transcarbamylase deficiency was made on the basis of the detection of orotic acid and uracil.


Structure and function of an ectopic Polycomb chromatin domain.
Polycomb group proteins (PcGs) drive target gene repression and form large chromatin domains. In Drosophila, DNA elements known as Polycomb group response elements (PREs) recruit PcGs to the DNA. We have shown that, within the invected-engrailed (inv-en) Polycomb domain, strong, constitutive PREs are dispensable for Polycomb domain structure and function. We suggest that the endogenous chromosomal location imparts stability to this Polycomb domain. To test this possibility, a 79-kb en transgene was inserted into other chromosomal locations. This transgene is functional and forms a Polycomb domain. The spreading of the H3K27me3 repressive mark, characteristic of PcG domains, varies depending on the chromatin context of the transgene. Unlike at the endogenous locus, deletion of the strong, constitutive PREs from the transgene leads to both loss- and gain-of function phenotypes, demonstrating the important role of these regulatory elements. Our data show that chromatin context plays an important role in Polycomb domain structure and function.


Optimization of cell growth on palmitoyl-hyaluronan knitted scaffolds developed for tissue engineering applications.
Polysaccharides meet several criteria for a suitable biomaterial for tissue engineering, which include biocompatibility and ability to support the delivery and growth of cells. Nevertheless, most of these polysaccharides, for example dextran, alginate, and glycosaminoglycans, are highly soluble in aqueous solutions. Hyaluronic acid hydrophobized by palmitic acid and processed to the form of wet-spun fibers and the warp-knitted textile scaffold is water non-soluble, but biodegradable material, which could be used for the tissue engineering purpose. However, its surface quality does not allow cell attachment. To enhance the biocompatibility the surface of palmitoyl-hyaluronan was roughened by freeze drying and treated by different cell adhesive proteins (fibronectin, fibrinogen, laminin, methacrylated gelatin and collagen IV). Except for collagen IV, these proteins covered the fibers uniformly for an extended period of time and supported the adhesion and cultivation of dermal fibroblasts and mesenchymal stem cells. Interestingly, adipose stem cells cultivated on the fibronectin-modified scaffold secreted increasing amount of HGF, SDF-1, and VEGF, three key growth factors involved in cardiac regeneration. These results suggested that palmitoyl-hyaluronan scaffold may be a promising material for various applications in tissue regeneration, including cardiac tissue repair. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1488-1499, 2018.


The Vitamin D Standardization Program (VDSP) Manual for Retrospective Laboratory Standardization of Serum 25-Hydroxyvitamin D Data.
Low concentrations of total 25-hydroxyvitamin D [25(OH)D], the principal biological measure of vitamin D status, have been associated with clinical and public health outcomes. The determination of levels under which there is an increase in the risk of disease, as well as comparisons across populations, have been difficult to establish due the large assay variability in measuring 25(OH)D. Accordingly, the Vitamin D Standardization Program (VDSP) includes the retrospective standardization of existing 25(OH)D values collected by epidemiological and clinical studies, as well as clinical trials, as one of its main objectives. We introduce methodology developed by the VDSP that can be used to standardize the measurement of time-stable analytes, including 25(OH)D, in samples that have been banked and maintained appropriately. Sample size estimation formulae are first applied to calculate the required number of banked blood samples to be reanalyzed using either of two approaches. In the first approach, existing samples are remeasured using the current measurement procedure, and an equation relating "old" to "current" measurements is obtained. A second set of sera, usually 40-50 single-donor serum samples, are measured with the current measurement procedure and an assay traceable to a reference measurement procedure and/or certified reference materials, which yields a second calibration equation. These two equations are combined to produce standardized levels from the original old values. This approach is necessary when study restrictions prevent serum samples from being shipped to an external laboratory and is illustrated with samples from the Canadian Health Measures Survey. When serum samples are permitted to be shared with other laboratories, or the study investigators can carry out the measurements with a traceable assay, a single calibration equation method is used. Existing samples are selected and remeasured using the available traceable assay. We outline the statistical theory supporting the VDSP protocol and provide implementation examples. The methods proposed are generalizable to any instance in which banked specimens have been properly prepared and stored and the analyte of interest is stable under those conditions.


Loss-of-Function PCSK9 Mutations Are Not Associated With Alzheimer Disease.
Hypercholesterolemia is a major risk factor for the late-onset form of Alzheimer disease (AD). Loss-of-function (LOF) mutations of PCSK9 and PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and have been associated with a reduced risk of cardiovascular disease. The aim of this study was to examine the effect of PCSK9 LOF variants on risk and age of onset of AD. A total of 878 participants (410 controls and 468 AD cases) from the Quebec Founder Population were included in the study. Fifty-four (6.2%) participants carried the R46L mutation, whereas 226 (26.2%) participants carried the InsLEU mutation. There was no protective or no deleterious effect of carrying PCSK9 LOF mutations on AD prevalence nor on age of onset, even when stratified by apolipoprotein E epsilon 4 genotype or by gender. Our data indicate that carrying PCSK9 LOF mutations has a neutral effect on neurocognitive health and the prevalence of AD.


[Unplanned pregnancies among women soldiers in the IDF--an overview].
According to the Security Service Law in Israel, a pregnant soldier serving her compulsory military service, who decides to continue with the pregnancy, is discharged from military service. If she wishes to terminate the pregnancy (TOP) and continue serving in the army, she is referred to a civilian pregnancy termination committee. This article aims to examine the incidence of pregnancies amongst soldiers during their compulsory military service (ages 18-20 years) and characterize the populations at risk. Data reflecting yearly incidence of pregnancies, number of TOPs, discharges from military duty as a result of continuation of pregnancy and missed abortions amongst soldiers during their compulsory military duty were derived from the military social services records for the period 1997-2003. Socio-demographic variables, number of prior pregnancies, age of pregnancy, means of TOP, relationship with the other parent and his involvement regarding the pregnancy, were obtained from military records between the years 2002-2003. The reported yearly incidence of pregnancies in 1997 was 18.6 per 1000 soldiers during their compulsory military service. In 2003, the incidence rose to 21.5 per 1000. The incidence of continuation of pregnancy, TOPs and missed abortions remained unchanged. Number-wise, the pregnancies occurred most often in Israeli-born, high-school educated young women. When stratifying by country of birth, however, the percentage of pregnancies within subgroups varied significantly. Half of the pregnancies were terminated by pharmaceutical means. In the majority of cases, the pregnancy resulted from a relationship lasting over half a year with a male partner, who was aware of the pregnancy and involved with the decisions regarding its outcome. In recent years there has been a rise in the reported yearly incidence of pregnancies among soldiers aged 18-20 years serving their compulsory military service. These findings reiterate the need to increase the efforts in implementing sex education programs amongst educators and the responsible military authorities.


Gunshot wounds to the spine in adolescents.
The incidence of spinal instability after penetrating gunshot wounds to the spine in adolescents is unknown. We describe our experience over a 15-year period. Hospital records were reviewed retrospectively. After injury and emergency care, patients were transferred to a rehabilitation facility. Examinations were completed using the American Spinal Injury Association and Frankel scales on admission, discharge, and 6 and 12 months after injury. Severity of injury was described by: 1) degree of neurological damage, 2) degree of preserved neurological function, and 3) presence of instability. Sixty patients were identified with a mean age 15.6 years (+/- 2.7 yr). Twelve patients had cervical, 31 thoracic, and 17 lumbosacral injuries. No operative treatments were used in their care. Thirty-four patients had complete neurological deficits. Mean acute hospitalization was 21.1 days (+/- 22.8 d), and mean rehabilitation stay was 86.3 days (+/- 48.9 d), for a total hospitalization of 107.4 days (+/- 65.9 d). At 1 year, 19 patients were ambulatory and 53 were autonomous. Despite the presence of bony involvement in all, no evidence of spinal instability was noted on follow-up dynamic imaging. Even in two patients with apparent two-column disruption, no instability was noted. At 1-year follow-up, significant (nonfunctional) improvement was noted in the neurological examination (P < 0.0001). Improvements were most notable in those patients with cervical injuries, followed by thoracic and lumbar injuries. After penetrating gunshot wounds to the spine, patients at 1-year follow-up examinations have evidence of significant, but nonfunctional, improvement. No evidence of spinal instability was noted in this study, and no surgical intervention was required.


Steady state relations between control proteins regulating the formation of the alternative pathway C3 convertase.
A steady state algebraic Mass Action analysis of the factors controlling the concentration of the alternative pathway C3 convertase is presented. The positive feedback loop does not make this portion of the complement system insensitive to variation in control protein concentrations; on the contrary, a hyperbolic relationship is revealed between C3 convertase and a complex product of the control protein concentrations which contains some mathematical non-linearities. The consequences of this relationship are explored. It is found that variations in the concentration of any one control protein will have an effect which can only be predicted if its initial concentration and those of the other control proteins are known. The system is capable of responding with a considerable range of amplitudes to a given signal which raises the question as to whether the feedback loop confers biological advantage, not only by augmenting the activation of C3 to C3b, but through its potential for flexibility in responding to an activating stimulus. The analysis may also prove useful in the design and evaluation of experiments to determine the reaction rate constants governing the interactions between the control proteins in the fluid phase in vitro.


Identification of flavonoids in Dendrobium huoshanense and comparison with those in allied species of Dendrobium by TLC, HPLC and HPLC coupled with electrospray ionization multi-stage tandem MS analyses.
Dendrobium huoshanense, a unique species in the genus Orchidaceae, is only found in China and is known as "mihu". Due to the lack of quality control, the use of D. huoshanense in the herbal market has been limited. In this study, methods based on thin-layer chromatography, high-performance liquid chromatography and high-performance liquid chromatography coupled with electrospray ionization multi-stage tandem mass spectrometry were used to identify the flavonoids in D. huoshanense and distinguish this species from other Dendrobium species. Using thin-layer chromatography, a characteristic band was observed for D. huoshanense, and this band was absent from the thin-layer chromatography plates of other Dendrobium species. Then, using high-performance liquid chromatography, nine peaks of flavonoids were observed in the chromatograms of ten batches of D. huoshanense. Ultimately, 22 flavonoids in D. huoshanense were identified by multi-stage tandem mass spectrometry, and 11 of these compounds are being reported from D. huoshanense for the first time. In addition, two compounds both with molecular weights of 710, were identified as being unique to D. huoshanense; one of these compounds, apigenin-6-C-α-L-rhamnosyl-(1→2)-β-D-glucoside-8-C-α-L-arabinoside, was proven to be responsible for the characteristic thin-layer chromatography band of D. huoshanense. These analysis methods can be applied for the identification and quality control of D. Huoshanense.


Structure of the PSD-95/MAP1A complex reveals a unique target recognition mode of the MAGUK GK domain.
The PSD-95 family of membrane-associated guanylate kinases (MAGUKs) are major synaptic scaffold proteins and play crucial roles in the dynamic regulation of dendritic remodelling, which is understood to be the foundation of synaptogenesis and synaptic plasticity. The guanylate kinase (GK) domain of MAGUK family proteins functions as a phosphor-peptide binding module. However, the GK domain of PSD-95 has been found to directly bind to a peptide sequence within the C-terminal region of neuronal-specific microtubule-associated protein 1A (MAP1A), although the detailed molecular mechanism governing this phosphorylation-independent interaction at the atomic level is missing. In the present study, we determine the crystal structure of PSD-95 GK in complex with the MAP1A peptide at 2.6-Å resolution. The complex structure reveals that, unlike a linear and elongated conformation in the phosphor-peptide/GK complexes, the MAP1A peptide adopts a unique conformation with a stretch of hydrophobic residues far from each other in the primary sequence clustering and interacting with the 'hydrophobic site' of PSD-95 GK and a highly conserved aspartic acid of MAP1A (D2117) mimicking the phosphor-serine/threonine in binding to the 'phosphor-site' of PSD-95 GK. We demonstrate that the MAP1A peptide may undergo a conformational transition upon binding to PSD-95 GK. Further structural comparison of known DLG GK-mediated complexes reveals the target recognition specificity and versatility of DLG GKs.


Early thyroidectomy for medullary thyroid carcinoma in children and young adults with the multiple endocrine neoplasia type 2A (MEN 2A) syndrome.
A South African family, at risk for the multiple endocrine neoplasia type 2A (MEN 2A) syndrome, was identified. The Bloemfontein MEN Study Group was founded, inter alia, to study the effects of early detection of medullary carcinoma of the thyroid (MTC) and treatment by total thyroidectomy in children and young adults with MEN 2A. Genotypes were identified by DNA probe and MTC diagnosed by basal and stimulated calcitonin levels. Between 1986 and 1989, 10 members of the family underwent total thyroidectomy and central lymph node dissection for MTC. There were 6 female and 4 male patients (mean age 22,0 years; range 10 - 35 years). Histological examination of the resected thyroid revealed MTC in all patients; 8 had bilateral disease and 2 unilateral. Lymph nodes were negative for MTC in all patients. None of the patients suffered injury to the recurrent nerve, while 1 experienced transient hypoparathyroidism postoperatively. Replacement therapy is maintaining thyroid hormone levels in all patients. Screening should probably begin at the age of 1 year, and total thyroidectomy should be performed when an elevated calcitonin level is observed.


Computational investigation of surface freezing in a molecular model of water.
Water freezes in a wide variety of low-temperature environments, from meteors and atmospheric clouds to soil and biological cells. In nature, ice usually nucleates at or near interfaces, because homogenous nucleation in the bulk can only be observed at deep supercoolings. Although the effect of proximal surfaces on freezing has been extensively studied, major gaps in understanding remain regarding freezing near vapor-liquid interfaces, with earlier experimental studies being mostly inconclusive. The question of how a vapor-liquid interface affects freezing in its vicinity is therefore still a major open question in ice physics. Here, we address this question computationally by using the forward-flux sampling algorithm to compute the nucleation rate in a freestanding nanofilm of supercooled water. We use the TIP4P/ice force field, one of the best existing molecular models of water, and observe that the nucleation rate in the film increases by seven orders of magnitude with respect to bulk at the same temperature. By analyzing the nucleation pathway, we conclude that freezing in the film initiates not at the surface, but within an interior region where the formation of double-diamond cages (DDCs) is favored in comparison with the bulk. This, in turn, facilitates freezing by favoring the formation of nuclei rich in cubic ice, which, as demonstrated by us earlier, are more likely to grow and overcome the nucleation barrier. The films considered here are ultrathin because their interior regions are not truly bulk-like, due to their subtle structural differences with the bulk.


Decoding the grammar of transcriptional regulation from RNA polymerase measurements: models and their applications.
The genomic revolution has indubitably brought about a paradigm shift in the field of molecular biology, wherein we can sequence, write and re-write genomes. In spite of achieving such feats, we still lack a quantitative understanding of how cells integrate environmental and intra-cellular signals at the promoter and accordingly regulate the production of messenger RNAs. This current state of affairs is being redressed by recent experimental breakthroughs which enable the counting of RNA polymerase molecules (or the corresponding nascent RNAs) engaged in the process of transcribing a gene at the single-cell level. Theorists, in conjunction, have sought to unravel the grammar of transcriptional regulation by harnessing the various statistical properties of these measurements. In this review, we focus on the recent progress in developing falsifiable models of transcription that aim to connect the molecular mechanisms of transcription to single-cell polymerase measurements. We discuss studies where the application of such models to the experimental data have led to novel mechanistic insights into the process of transcriptional regulation. Such interplay between theory and experiments will likely contribute towards the exciting journey of unfurling the governing principles of transcriptional regulation ranging from bacteria to higher organisms.


Dietary administration of tetrodotoxin and its putative biosynthetic intermediates to the captive-reared non-toxic Japanese fire-bellied newt, Cynops pyrrhogaster.
The origin of tetrodotoxin (TTX) in amphibians has long been disputed. In this study, TTX and its putative biosynthetic intermediates or shunt compounds (4,9-anhydro-10-hemiketal-5-deoxyTTX and Cep-242) were dietary administered to the captive-reared, non-toxic Japanese fire-bellied newt, Cynops pyrrhogaster. After 4 weeks, the ingested compounds were detected mainly in the newt body using liquid chromatography-mass spectrometry (LC-MS), while these compounds were not converted into other TTX analogues in newts.


Relationship of ascorbic acid levels of blood and gingival tissue with response to periodontal therapy.
The effect of ascorbic acid megadoses on gingival clinical parameters and vitamin content of blood and gingival tissue was studied. 10 nondeficient individuals, carefully matched according to age, periodontal status, and oral hygiene level, were divided into 2 groups: one received 250 mg q.i.d. of ascorbic acid and the other a placebo. After 1 week on the tablet all patients were scaled and root planed and received oral hygiene instructions. Blood samples and clinical parameters were obtained at baseline and 2, 6, and 7 weeks after. A gingival biopsy was taken at week 6. Correlations between the clinical parameters and the ascorbic acid levels at the different time periods revealed no significant differences between the vitamin and the placebo groups, therefore suggesting that the use of megadoses of vitamin C in normal human subjects does not have a predictable or strong effect on the gingival response to initial therapy.


Regioselective synthesis of isoxazole and 1,2,4-oxadiazole-derived phosphonates via [3 + 2] cycloaddition.
The results of the study on reactions of halogenoximes bearing (protected) functional groups or fluorinated substituents with various phosphorus-containing dipolarophiles are described. To control the regioselectivity of the reaction, vinylphosphonates bearing a leaving group (i.e. bromine or dialkylamino group) in the α or β position were used; 3,5- and 3,4-disubstituted isoxazoles were obtained in 47-80% and 63-75% yields, respectively. The reaction was also effective for the parent vinyl phosphonate and cyanophosphonate; in this case, the corresponding isoxazoline- and 1,2,4-oxadiazole-derived phosphonates were isolated in 55-69% and 34-73% yields, respectively. The utility of the products obtained was demonstrated by the preparation of direct conformationally restricted analogues of phosphohistidine.


The acquisition and retention of urinary catheterisation skills using surgical simulator devices: teaching method or student traits.
The acquisition of procedural skills is an essential component of learning for medical trainees. The objective of this study was to assess which teaching method of performing urinary catheterisation is associated with most efficient procedural skill acquisition and retention. We evaluated factors affecting acquisition and retention of skills when using simulators as adjuncts to medical training. Forty-two second year medical students were taught urinary catheter insertion using different teaching methods. The interactive group (n = 19) were taught using a lecture format presentation and a high fidelity human urinary catheter simulator. They were provided with the use of simulators prior to examination. The observer group (n = 12) were taught using the same method but without with simulator use prior to examination. The didactic group (n = 11) were taught using the presentation alone. Student characteristics such as hand dexterity and IQ were measured to assess for intrinsic differences. All students were examined at four weeks to measure skill retention. Catheter scores were significantly higher in the interactive group (p < 0.005). Confidence scores with catheter insertion were similar at index exam however were significantly lower in the didactic group at the retention testing (p < 0.05). Retention scores were higher in the interactive group (p < 0.001). A significant positive correlation was observed between laparoscopy scores and time to completion with overall catheter score (p < 0.05). Teaching method, spatial awareness and time to completion of laparoscopy were significantly associated with higher catheter scores at index exam (p = 0.001). Retention scores at 4 weeks were significantly associated with teaching method and original catheter score (p = 0.001). The importance of simulators in teaching a complex procedural skill has been highlighted. Didactic teaching method was associated with a significantly higher rate of learning decay at retention testing.


Apparent affinity estimates of rimonabant in combination with anandamide and chemical analogs of anandamide in rhesus monkeys discriminating Delta9-tetrahydrocannabinol.
Anandamide and Delta(9)-tetrahydrocannabinol (Delta(9)-THC) sometimes produce different discriminative stimulus effects and, therefore, appear to differ in their mechanism of action. In order to understand the widespread use of cannabis and the therapeutic potential of cannabinoids, mechanisms responsible for behavioral effects need to be identified. Drug discrimination was used to compare the mechanism of action of Delta(9)-THC, anandamide, and two structural analogs of anandamide in rhesus monkeys. Monkeys discriminated Delta(9)-THC (0.1 mg/kg i.v.) from vehicle. Delta(9)-THC, anandamide, methanandamide, and arachidonylcyclopropylamide (ACPA) were administered i.v. alone and in combination with at least one dose of rimonabant. Schild analysis and single-dose apparent affinity estimates were used to estimate the potency of rimonabant as an antagonist of each cannabinoid; these values were compared to examine whether the same receptors mediated discriminative stimulus effects. Delta(9)-THC, ACPA, methanandamide, and anandamide produced greater than 96% of responses on the Delta(9)-THC lever. The ED(50) values were 0.024 mg/kg for Delta(9)-THC, 0.14 mg/kg for ACPA, 0.28 mg/kg for methanandamide, and 1.7 mg/kg for anandamide. The duration of action of Delta(9)-THC was 4-6 h and longer than the duration of action ACPA, methanandamide, and anandamide (i.e., each less than 50 min). Rimonabant surmountably antagonized the discriminative stimulus effects of each agonist, and the apparent affinity estimates (pA (2) and pK (B) values) were 6.24-6.83. Rimonabant can produce surmountable antagonism of the behavioral effects of not only Delta(9)-THC but also anandamide, methanandamide, and ACPA, and the interactions appear simple, competitive, and reversible. These cannabinoid agonists act at the same receptors to produce discriminative stimulus effects.


Left atrial mechanical functions in patients with anterior myocardial infarction: a velocity vector imaging-based study.
The contribution of the left atrium (LA) to left ventricular (LV) function increases in myocardial infarction (MI). To evaluate LA function by using volume measurements and a novel strain imaging method, namely velocity vector imaging (VVI), in patients with acute anterior MI. Twenty-four patients with previous anterior MI (aged 63.8 ± 4.2 years, 56% men) and 30 healthy controls (aged 60.7 ± 5.3 years, 60% men) were enrolled. LA volume measurements and VVI-derived LA peak systolic strain (S), strain rate (SRs), early diastolic (ESRd) and late diastolic strain rate (LSRd) were measured. LV diastolic function was analysed by pulsed wave-Doppler and tissue velocity ımaging. LA maximum volume index was increased in patients compared to controls (28.83 ± 7.2 vs. 19.72 ± 6.27 mL/m²,p = 0.0001). As LA active emptying volume index and fraction were increased (6.16 ± 0.7 vs. 5.46 ± 0.99 mL/m², p = 0.009 and 22.16 ± 3.07 vs. 16.78 ± 2.93%, p = 0.0001, respectively), passive emptying volume index and fraction were decreased in the patient group (6.09 ± 0.57 vs. 7.57 ± 0.61 mL/m², p = 0.0001 and 45.76 ± 6.86 vs. 56.45 ± 5.36%, p = 0.0001, respectively). However, total emptying volume index of the LA was similar between the two groups. VVI-derived LA peak systolic S, SRs and ESRd were impaired in the patient group. LA LSRd was similar between the groups. LA active emptying fraction was positively correlated with LV diastolic dysfunction and negatively correlated with LV systolic dysfunction. We demonstrated increased LA booster function and decreased LA conduit and reservoir functions in patients with prior anterior MI. Improvement in LA booster function correlated with the degree of LV systolic and diastolic dysfunction, suggesting a compensatory response of the LA.


Staged repair for aortic arch reconstruction and intracardiac repair following bilateral pulmonary artery banding in 3 critical patients.
Bilateral pulmonary artery banding has been performed as a first palliation for hypoplastic left heart syndrome with a poor preoperative condition. We report 3 patients with aortic arch reconstruction and intracardiac repair following bilateral pulmonary artery banding in moribund patients after birth. Our patients successfully received arch reconstruction, pulmonary debanding and patch closure of the ventricular septal defect at the age of 2 or 3 months after birth with a body weight of 3.5 and 4.5 kg, respectively. No postoperative neurological deficits were observed, and postoperative morbidity was significantly reduced. More than 75% of cerebral oxygenation may provide higher urinary output due to higher renal blood flow through collateral circulation. This technique reduces the risk of perioperative neurological damage.


Drs. Konsta and van der Horst-Bruinsma reply.
We thank Dr. Slouma et al1 for their earnest interest in our recent article, which examined the prevalence and radiographic progression of hip involvement in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor inhibitors (TNFi).2.


Phospholipids of New Zealand Edible Brown Algae.
Edible brown algae have attracted interest as a source of beneficial allenic carotenoid fucoxanthin, and glyco- and phospholipids enriched in polyunsaturated fatty acids. Unlike green algae, brown algae contain no or little phosphatidylserine, possessing an unusual aminophospholipid, phosphatidyl-O-[N-(2-hydroxyethyl) glycine], PHEG, instead. When our routinely used technique of 31P-NMR analysis of phospholipids was applied to the samples of edible New Zealand brown algae, a number of signals corresponding to unidentified phosphorus-containing compounds were observed in total lipids. NI (negative ion) ESI QToF MS spectra confirmed the presence of more familiar phospholipids, and also suggested the presence of PHEG or its isomers. The structure of PHEG was confirmed by comparison with a synthetic standard. An unusual MS fragmentation pattern that was also observed prompted us to synthesise a number of possible candidates, and was found to follow that of phosphatidylhydroxyethyl methylcarbamate, likely an extraction artefact. An unexpected outcome was the finding of ceramidephosphoinositol that has not been reported previously as occurring in brown algae. An uncommon arsenic-containing phospholipid has also been observed and quantified, and its TLC behaviour studied, along with that of the newly synthesised lipids.


Biomass behaviour in a conventional activated sludge system treating olive mill wastewater.
The current work aims to study the biomass behaviour in a continuous mode activated sludge system (ASS) treating olive mill wastewater (OMWW) through an increasing OMWW food to microorganism ration (F/M). To this end, the biomass growth, the specific oxygen uptake rate (SOUR), microbial characterization, sludge volume index (SVI) as well as COD and phenolic compounds removal efficiencies were examined over time. Results showed a successful growth of the biomass that reached 6.79 gTSS l-1 and 5.42 gVSS l-1. Its viability, its adaptability, and its good physiological activity were confirmed by the obtained result of SOUR with an average of 9.95 mgO2 gVSS-1h-1, as well as aerobic microbial population characterization in terms of aerobic revivable bacteria at 22°C and 37°C, Pseudomonas sp., mould and yeast and total fungi. The concentration of these strains characterized by their ability to degrade effectively COD and phenolic compounds increased significantly (p < .05) over time. This demonstrated a great promptness in response to the increasing OMWW mass ratio. For all treatment steps, removal efficiencies were high and reached 95% of COD and 93% of phenolic compounds, also the flocs settleability shown by SVI measurement was optimal.


DFT prediction of multitopic N-heterocyclic carbenes using Clar's aromatic sextet theory.
Existence of several multitopic N-heterocyclic carbene (NHC) ligands with up to four carbene centers have been predicted on the basis of Clar's aromatic sextet theory. Assessment on stability and reactivity of NHCs was made by quantifying aromaticity, aromatic stabilization energy (E(aroma)), strength of carbene lone pair, proton affinity, and CuCl binding energy. On NICS(0) and HOMA scales of aromaticity, several NHCs showed high aromaticity, while E(aroma) (17.2-19.4 kcal/mol) indicated substantial stability for the N-heterocycle. Homodesmotic reactions suggested that heat of formation of most of the newly designed carbenes is very close to that of the existing bis-NHCs. Designing a multitopic ligand through branching via C(sp3) linkage was very effective as it improved the stability of the carbene. Electrostatic potential minimum (V(min)) at the carbene lone pair suggested that annelation of heterocycle to a benzenoid ring or branching through C(sp3) linkage can only marginally influence the electron donating power of the ligand. Hence, all multitopic NHCs showed proton affinity (252.3-267.4 kcal/mol) and CuCl binding energy (62.9-66.6 kcal/mol) very close to those of 1,3-dimethylimidazolidine-2-ylidene (1). It has also been demonstrated that branched multitopic 3-dimensional NHCs are attractive for designing metal-organic framework with narrow (1-1.5 nm) cage/pore size.


Brain correlates of memory reconsolidation: A role for the TPJ.
In this paper, we investigate the process by which new experiences reactivate and potentially update old memories. Such memory reconsolidation appears dependent on the extent to which current experience deviates from what is predicted by the reactivated memory (i.e. prediction error). If prediction error is low, the reactivated memory is likely to be updated with new information. If it is high, however, a new, separate, memory is more likely to be formed. The temporal parietal junction TPJ has been shown across a broad range of content areas (attention, social cognition, decision making and episodic memory) to be sensitive to the degree to which current information violates the observer's expectations - in other words, prediction error. In the current paper, we investigate whether the level of TPJ activation during encoding predicts if the encoded information will be used to form a new memory or update a previous memory. We find that high TPJ activation predicts new memory formation. In a secondary analysis, we examine whether reactivation strength - which we assume leads to a strong memory-based prediction - mediates the likelihood that a given individual will use new information to form a new memory rather than update a previous memory. Individuals who strongly reactivate previous memories are less likely to update them than individuals who weakly reactivate them. We interpret this outcome as indicating that strong predictions lead to high prediction error, which favors new memory formation rather than updating of a previous memory.


Rhythmic Music Training's Effect on Syntactic Structure Processing among Malay Adolescents with Syntactic Specific Language Impairment.
Adolescents with syntactic specific language impairment (S-SLI) fail to comprehend which object questions. We hypothesised that rhythmic music training is more effective in treating this condition than conventional methods because music is often perceived as having a clear, isochronous beat or pulse. Thus, this study aims to investigate the effects of rhythmic music training on the syntactic structure processing of Malay which questions among native adolescents. In this research study, the participants were three groups of Malay adolescents aged 13 years old-15 years old: i) adolescents with S-SLI with music training, ii) adolescents with S-SLI without music training and iii) typically developing adolescents. Before and after music training, the participants were given a sentence-picture matching task. Accuracy measures and reaction times were captured using E-Prime 2.0. The results indicated that with music training, the accuracy and reaction time associated with which object questions among the two SLI groups were significantly higher and lower, respectively. The implications of using rhythmic music training in enhancing syntactic structure processing are also discussed.


Enzymatic Polymerization of Furan-2,5-Dicarboxylic Acid-Based Furanic-Aliphatic Polyamides as Sustainable Alternatives to Polyphthalamides.
Furan-2,5-dicarboxylic acid (FDCA)-based furanic-aliphatic polyamides can be used as promising sustainable alternatives to polyphthalamides (semiaromatic polyamides) and be applied as high performance materials with great commercial interest. In this study, poly(octamethylene furanamide) (PA8F), an analog to poly(octamethylene terephthalamide) (PA8T), is successfully produced via Novozym 435 (N435)-catalyzed polymerization, using a one-stage method in toluene and a temperature-varied two-stage method in diphenyl ether, respectively. The enzymatic polymerization results in PA8F with high weight-average molecular weight (M̅(w)) up to 54000 g/mol. Studies on the one-stage enzymatic polymerization in toluene indicate that the molecular weights of PA8F increase significantly with the concentration of N435; with an optimal reaction temperature of 90 °C. The temperature-varied, two-stage enzymatic polymerization in diphenyl ether yields PA8F with higher molecular weights, as compared to the one-stage procedure, at higher reaction temperatures. MALDI-ToF MS analysis suggests that eight end groups are present in the obtained PA8F: ester/amine, ester/ester, amine/amine, acid/amine, ester/acid, acid/acid, ester/amide, and no end groups (cyclic). Compared to PA8T, the obtained PA8F possesses a similar Tg and similar crystal structures, a comparable Td, but a lower Tm.


[Basal ganglia calcification: clinical manifestations and diagnostic evaluation].
Physiological intracranial calcification occurs in about 0,3-1,5% of cases. It is asymptomatic and is detected incidentally by neuroimaging. Pathological basal ganglia calcification is due to various causes, such as: metabolic disorders, infectious and genetic diseases and other. Hypoparathyroidism and pseudohypoparathyroidism are the most common causes of pathological basal ganglia calcification. Besides tetany and seizures this condition is presented by parkinsonism and dementia. Such parkinsonism doesn't respond to drugs containing levodopha. Infections (toxoplasmosis, rubella, cytomegalovirus, cysticercosis, AIDS) give multiple and asymmetric intracranial calcification. Inherited and neurodegenerative diseases cause symmetrical, bilateral basal ganglia calcification which is not related to metabolic disorders (blood calcium level and other), those are: Cockayne syndrome, tuberous sclerosis, Fahr's syndrome, Down syndrome and other. We observed some cases of basal ganglia calcification and studied clinical manifestations and treatment tolerance of this pathological condition. Since adequate treatment of hypoparathyroidism may lead to marked clinical improvement, serum concentration of calcium, phosphorus, and parathyreoid hormone is suggested to be determined in all individuals with calcification of the basal ganglia to rule out hypoparathyroidism. Basal ganglia calcification in young patient with acute hepatitis may be result of Wilson disease.


Intramolecular radical cyclization-ring-closing metathesis approach to fused polycyclic ethers. Convergent synthesis and conformational analysis of the (E)FGH ring system of ciguatoxin.
A convergent synthetic route to the (E)FGH ring system 4 of ciguatoxins, the causative toxins for ciguatera fish poisoning, has been developed. The synthesis features convergent coupling to form dioxane acetal, regioselective acetal cleavage by diethylaluminum phenylthiolate or diisobutylaluminum phenylselenolate followed by intramolecular radical cyclization to construct the oxepane ring G, and a ring-closing metathesis reaction to form the hexahydrooxonine ring F. The hexahydrooxonine ring F of tetracyclic model system 4 existed as a 5:1 equilibrium mixture of two conformers (UP and DOWN conformers), with the UP one predominating. This is the first illustration that reproduces the preference for the UP conformer over the DOWN one, which preference was observed for natural ciguatoxins.


Adiponectin may play a part in the pathogenesis of diabetic retinopathy.
To measure plasma adiponectin concentrations in patients with type 2 diabetes and to investigate any association with the severity of diabetic retinopathy, because adiponectin seems to be an important modulator for metabolic and vascular diseases. Seventy-four patients (mean age 46.8+/-5.1 years; body mass index (BMI), 26.8+/-2.10 kg/m(2)) and 54 healthy volunteers (mean age 46.8+/-5.4 years; BMI 26.47+/-2.33 kg/m(2)) were included. Adiponectin concentrations in the patients were significantly lower than those in controls (4.71+/-2.11 microg/ml for patients, n=74; 15.95+/-3.72 microg/ml for controls, n=54; P<0.001). In the patients group there was a significant negative correlation between adiponectin and homeostasis model assessment index (r=-0.318, P=0.006 respectively). Plasma adiponectin concentrations in patients with proliferative diabetic retinopathy (n=20; 3.16+/-1.83 microg/ml) or non-proliferative diabetic retinopathy (n=24; 3.97+/-1.47 microg/ml, P=0.014) were significantly lower than those in patients without diabetic retinopathy (n=30; 6.30+/-1.57 microg/ml, P=0.001). When the presence of diabetes was defined as the final variable in the conditional logistic regression model with the adiponectin concentration as the continuous variable, adiponectin was significantly involved in the model. The results show that adiponectin concentrations are lower in patients with type 2 diabetes and that the concentrations are associated with the severity of diabetic retinopathy. Our findings suggest that adiponectin may take part in the pathogenesis of diabetic retinopathy.


Isolation of Borrelia burgdorferi from the blood of a bushy-tailed wood rat in California.
Borrelia burgdorferi was isolated from the blood of a bushy-tailed wood rat (Neotoma cinerea) from northeastern California, USA. This is the first isolation of live B. burgdorferi spirochetes from a wild animal in California. Spirochetes were observed in stained tissues from the brain, liver, spleen, and kidneys.


Preliminary evidence for an automatic link between sex and power among men who molest children.
Understanding critical motivational processes of sexual offenders may ultimately provide important clues to more effective treatments. Implicit, automatic cognitive processes have received minimal attention; however, a lexical decision experiment revealed automatic links between the concepts of power and sex among participants who self-reported attraction to sexual aggression. The current study replicates this experiment with a group of male child molesters and forensic and analogue controls. Subliminally presented sex words elicited a facilitation effect for power words among child molesters only; that is, sex to power associations were evident, as well as a trend for the reverse. These results provide preliminary evidence for an automatic sex-power association in child molesters and may point to a crucial pathological link in the cognitive schemata of sex offenders. As well, the current study suggests that paradigms from cognitive psychology may contribute to multimodal (risk) assessment of sexual offenders.


[Volume changes of intervertebral disc and vertebral body after dorsal fusion].
Even today, different opinions can be found concerning realignment loss of the adjoining intervertebral disc after fracture followed by dorsal fusion. There is still disagreement on intervertebral disc excision and the subsequent necessity of intercorporal fusion. In this context, fractures of the thoracolumbar transition and its operative repair via instrumented bisegmental dorsal fusion at T11 - L1 and T12 - L2, respectively, have been examined. Immediately after the accident and after removal of the implant, sagittal MR images (T1-, TE-, T2-weighted) with a standard 4 mm slice thickness were made. Eighteen patients with fractures of the thoracolumbar transition (A3 and B1 according to the AO classification) could be included in this study. All fractures were of traumatic genesis. The implant was removed after an average of ten months. Allowing for planimetric measuring errors, our analysis generated a 14 % volume decrease of the upper and a 15 % volume decrease of the lower intervertebral disc. A volume change of 3 % in the bridged or fractured vertebral body was found to be without any verifiable significance. Tendentially, a slight volume loss of both adjacent intervertebral discs could be observed. In our opinion, the realignment loss after a mean ten months cannot be explained by the volume changes of the discs alone. The creeping of the intervertebral disc into the adjacent vertebral body accounts for the post-traumatic malalignment.


Delivery of E. coli Nissle to the mouse gut by mucoadhesive microcontainers does not improve its competitive ability against strains linked to ulcerative colitis.
For patients with ulcerative colitis (UC), administration of the probiotic E. coli Nissle (EcN) holds promise for alleviation of disease symptoms. The mechanisms are unclear, but it has been hypothesised that a capacity of the probiotic to outcompete potentially detrimental UC-associated E. coli strains plays an important role. However, this could previously not be confirmed in a mouse model of competition between EcN and two UC-associated strains, as reported by Petersen et al. 2011. In the present study, we re-evaluated the idea, hypothesising that delivery of EcN by a micro device dosing system (microcontainers), designed for delivery into the intestinal mucus, could support colonisation and confer a competition advantage compared to classical oral dosing. Six groups of mice were pre-colonised with one of two UC-associated E. coli strains followed by oral delivery of EcN, either in capsules containing microcontainers with freeze-dried EcN powder, capsules containing freeze-dried EcN powder, or as a fresh sucrose suspension. Co-colonisation between the probiotic and the disease-associated strains was observed regardless of dosing method, and no competition advantages linked to microcontainer delivery were identified within this setup. Other approaches are thus needed if the competitive capacity of EcN in the gut should be improved.


Effect of an oral alpha 2-adrenergic blocker (MK-912) on pancreatic islet function in non-insulin-dependent diabetes mellitus.
We used MK-912, a potent new selective alpha 2-adrenergic receptor antagonist that is active orally, to study the effect of short-term, selective alpha 2-blockade on fasting plasma glucose (FPG) and pancreatic islet function in non-insulin-dependent diabetes (NIDDM). Ten asymptomatic patients with NIDDM received either a single oral dose of MK-912 (2 mg) or placebo in a double-blind, cross-over study. B-cell function was measured by the acute insulin response (AIR) to glucose (1.66 mmol/kg intravenously [IV]) and by the AIR to arginine (5 g IV) during a hyperglycemic glucose clamp at a mean glucose level of 32.1 mmol/L to provide an estimation of maximal B-cell secretory capacity. A-cell function was estimated by the acute glucagon response (AGR) to arginine during the glucose clamp. Effective alpha 2-adrenergic blockade was apparently achieved, as there were substantial increases of plasma norepinephrine (NE) (P less than .01) and both systolic blood pressure (SBP) (P less than .01) and diastolic blood pressure (DBP) (P less than .05) after treatment with MK-912, but not after placebo. MK-912 caused a significant (P less than .05) although modest decrease of FPG that was associated with a small increase of fasting plasma insulin (P less than 0.01), C-peptide (P less than .05), and glucagon (P less than .01). FPG and hormone levels remained unchanged after placebo. MK-912 tended to increase the AIR (P = .06) and the C-peptide response (P = .07) to glucose compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)


Humoral immune response in convalescent COVID-19 people with multiple sclerosis treated with high-efficacy disease-modifying therapies: A multicenter, case-control study.
To determine the influence of high-efficacy disease modifying therapy (DMT) on the development of IgG SARS-CoV-2 antibody response in COVID-19 convalescent people with multiple sclerosis (pwMS). Seventy-four pwMS taking high-efficacy DMTs (specifically natalizumab, fingolimod, alemtuzumab, ocrelizumab, cladribine and ublituximab) and diagnosed with COVID-19 and 44 healthy persons (HC) were enrolled. SARS-CoV2 antibodies were tested with Elecsys® Anti-SARSCoV-2 S assay. pwMS taking high-efficacy DMTs had a significantly higher chance of having negative titer of SARS-CoV2 antibodies compared to healthy controls (33 negative pwMS [44.6%] compared to one negative HC [2.3%], p < 0.001). pwMS taking B-cell depleting therapy (ocrelizumab and ublituximab) had a significantly higher chance of having negative titer of SARS-CoV2 antibodies compared to pwMS on all other DMTs (29 negative pwMS on B-cell therapy [64.4%] compared to four negative pwMS on all other DMTs [13.8%], p < 0.001). Out of other DMTs, two (33.3%) pwMS taking fingolimod and two (16.7%) pwMS taking cladribine failed to develop IgG SARS-COV-2 antibodies. B-cell depleting therapy independently predicted negative titer of IgG SARS-CoV-2 antibody (Exp[B] =0.014, 95%CI 0.002-0.110, p < 0.001). A significant proportion of convalescent COVID-19 pwMS on high-efficacy DMTs will not develop IgG SARS-CoV-2 antibodies. B-cell depleting therapies independently predict negative and low titer of IgG SARS-CoV-2 antibody.


SiRNA silencing of VEGF, IGFs, and their receptors in human retinal microvascular endothelial cells.
Vascular endothelial growth factor (VEGF) is a potent mitogen that regulates proliferation, migration, and tube formation of endothelial cells (EC). VEGF has recently become a target for severe retinopathy of prematurity (ROP) therapy. We tested the hypothesis that a specific VEGF isoform and/or receptor acts synergistically with insulin-like growth factor (IGF)-I to alter normal retinal microvascular EC angiogenesis and RNA interference can be used to reverse VEGF effects. We used small interfering RNA (SiRNA) transfection to target VEGF isoforms, IGFs, and their receptors in human retinal microvascular endothelial cells (HRECs). Media was collected at 24 and 48 hours post transfection for measurement of VEGF, sVEGFR-1 and IGF-1 levels; and HRECs were assessed for migration, tube formation, VEGF signaling genes, oxidative stress, and immune-reactivity. At 24 hours post transfection VEGF increased with VEGFR-2; sVEGFR-1 decreased with VEGF165, VEGFR-2, and IGF-1R; and IGF-I increased with VEGF189, VEGFR-1, IGF-2R, IGF+VEGF165, and IGF+VEGF121. IGF-I transfection with each VEGF isoform reduced sphere- forming and migration capacities with robust upregulation of caspase-9, COX-2, MAPK, PKC, and VEGF receptors. At 48 hours, the effects were reversed with a majority of genes downregulated, except with IGF-I and NP-1 transfection. Using RNA interference for targeted inhibition of VEGF isoforms in conjunction with IGF-I may be preferable for suppression of HREC overgrowth in vasoproliferative retinopathies such as ROP.


Self-efficacy is associated with walking ability in persons with diabetes mellitus and peripheral arterial disease.
Self-efficacy is a known predictor for behavior change. Little is known about the association of self-efficacy with walking ability in individuals with diabetes mellitus and peripheral arterial disease (PAD). The objective of this study was to determine the association of self-efficacy with walking ability in individuals with diabetes mellitus and PAD. In this cross-sectional study, baseline data were analyzed from individuals with diabetes mellitus type 1 or 2 and PAD who were enrolled in a walking intervention clinical trial. As part of the baseline assessment, individuals completed questionnaires to ascertain self-efficacy and co-existing illnesses. In addition, participants completed a treadmill walking test and a 6-minute walking test. A total of 145 individuals were enrolled (mean age 66.5 +/- 10.1 years) with diabetes mellitus and PAD; 45 (31%) were women. The mean ankle-bracial index was 0.70 (range - 0.18-2.20) and the mean glycosylated hemoglobin value was 7.1 (SD 1.2). The mean distance walked, as per the treadmill walking test, was 418 meters (SD 258) and the mean distance walked, as per the 6-minute walking test, was 272 meters (SD 74). As measured by the treadmill walking test and the 6-minute walking test, self-efficacy was associated with treadmill walking distance, coefficient 33.0 (95% CI 11.0, 55.1; p = 0.0036), and the 6-minute walking test, coefficient 10.4 (95% CI 3.0, 17.7; p = 0.0061), after adjusting for comorbidities, social habits, and disease severity. In conclusion, self-efficacy, a psychosocial mediator for behavior change, was significantly associated with walking ability in individuals with diabetes mellitus and PAD. Future studies should determine the benefits of targeting self-efficacy to improve adherence to walking therapy in patients with PAD.


Live high-frame-rate echocardiography.
We describe an advanced real-time high-speed echocardiographic system with live display while scanning. Images are acquired at rates up to 1000 per second for adult cardiac applications and are stored in computer memory. Images may be played back in slow motion or frame by frame to analyze cardiac motion at the millisecond time scale. Images are acquired using the T5 Duke University Phased Array Scanner that allows 32:1 hardware parallel processing in receive and uses a defocused transmit beam. Clinical scans of 70 patients at rates of 240 to 1000 fps showed adequate image quality for diagnostic purpose. We anticipate that high temporal resolution cardiac images will enable the realization of more accurate and new quantitative descriptors of cardiac function in disease and health.


Heating-Induced Transformation of Anatase TiO2 Nanorods into Rock-Salt TiO Nanoparticles: Implications for Photocatalytic and Gas-Sensing Applications.
Anatase TiO2 nanocrystals (NCs) play a vital role in photocatalytic applications due to their high catalytic activity and in gas-sensing applications due to their high chemical sensitivity. Here, we report the transformation at elevated temperature of anatase nanorods (NRs) with a length of 25 nm into rock-salt TiO nanoparticles with an average size of 9.2 ± 2.1 nm investigated by means of in situ heating in the transmission electron microscope. The NRs were completely transformed to titanium monoxide NCs after heating to a temperature of 1200 °C. We also identified an intermediate stage in the temperature range of 950-1200 °C, during which not only the anatase and rock-salt phases were found but also the brookite phase. Understanding of the phase and morphology evolution at high temperatures is of essence to the functionality of the NRs in various applications, as discussed in this work. Moreover, the high-temperature transformation to titanium monoxide is of interest as rock-salt TiO (γ-TiO) is known to exhibit superconducting properties. We propose the heating-induced transformation as a physical route to synthesize TiO NCs of very small size.


Food security in a world without borders.
The alleviation of poverty and the eradication of hunger and malnutrition are within reach. Considerable progress has been made over the past thirty years in reducing the numbers of the hungry, and projections over the next thirty years suggest that this progress will continue. The majority of developing countries have participated in this progress and have improved nutrition but there are significant regional differences. The current challenge is to build upon and accelerate the progress already made. Everyone is involved in this struggle against hunger and malnutrition, and to achieve these goals, global partnerships to enhance co-operation and co-ordination are being strengthened. Successful country experiences for improving food security and nutrition have demonstrated the importance of peace, political stability, and stable economic growth. There is also the need for increased foreign investment and increased ODA, particularly for African agriculture, debt relief, the better integration of LDCs in the global economy, their more secure access to markets and more equitable terms of trade, enhanced South-South co-operation, training and research and new high-yield and drought-resistant crop varieties. While all these have been commented on and recognised before, we must close the credibility gap in our political will by honouring our existing commitments for providing tangible benefits at the local level. For globalisation, the key issue is how the aggregate benefits of globalisation will be distributed and how to translate this into better nutrition. The LDCs, which are the most vulnerable and disadvantaged members of the international community, should be at the centre of this drive towards food security and take genuine ownership of policies, initiatives and activities to improve development. At the same time we need to succeed in making the developed world more aware of and responsive to the conditions of the LDCs. The most effective way to improve nutrition is through community nutrition programmes that encourage the full participation and co-operation of the entire community, maximise the utilisation of local resources, grasp the benefits of new technologies for productivity gains, involve multiple sectors and engage strong political commitment. The international community will be judged by its treatment of its most vulnerable members. The international community has repeatedly declared that it is dedicated to the eradication of poverty. Eliminating hunger and malnutrition is a vital first step. The political will to fight hunger and a firm commitment to invest in agriculture' and rural development are critical elements in any effort to achieve sustainable alleviation of hunger and poverty. This meeting and the WFS:FYL provide the additional impetus to meet the challenge of achieving food and nutritional security in a world without borders and free from hunger and malnutrition.


Goldenhar syndrome with various clinical manifestations.
Four case reports of children with clinical features of Goldenhar syndrome are described. Although the syndrome itself is not very rare, the occurrence in dizygotic twins and the presence of heart dextroposition and peripheral facial nerve palsy, which are rare associations, prompted the report of these cases.


Role of health technology assessment in the process of implementation of the EU Transparency Directive: relevant experience from Central Eastern European countries.
A total of 7 years after the addition of Poland, the Czech Republic and Hungary to the EU, the pricing and reimbursement regulations introduced in these countries are still considered to be not fully compliant with Directive 89/105/EEC, commonly referred to as the 'Transparency Directive' (TD). The TD aims to ensure the transparency of the pricing and reimbursement processes for medicinal products established by the member states. Among the most difficult barriers on the way to successful implementation of the TD discussed are meeting the timelines indicated by the TD, the implementation of objective and verifiable criteria for decisions, and the availability of remedies for negative decisions. Health technology assessment (HTA) has been introduced in to the reimbursement systems in Poland, the Czech Republic and Hungary almost simultaneously to their accession to the EU. Even though Central Eastern European (CEE) countries faced similar challenges during the transformation to a democratic system, certain differences in the extent to which HTA principles have been implemented in these countries could be distinguished. Hence, it is thought-provoking to consider the different views of HTA experts on the role of HTA in the adaptation of the TD in the CEE region. The key objective of this article will be to discuss whether the adaptation of HTA principles has supported or only triggered additional challenges in the process of successful implementation of the TD in the CEE region. In particular, the article will discuss whether the introduction of mandatory HTA recommendations or explicit willingness-to-pay threshold would encourage or discourage implementation of the TD. The importance of the independent HTA agency as a condition for successful introduction of the TD will also be debated.


Repair of head and neck defects with thin and double-lined pectoralis flaps.
The evolution of nondelayed , single-stage repairs of extensive ablative defects of the upper aerodigestive tract with thin, skin-lined pectoralis myogenous and myocutaneous flaps is described, with particular emphasis on technique and applicability. To date, 15 such modified flap reconstructions of the oral cavity, oropharynx, and pharyngoesophagus have been performed. Other than one instance of flap failure, no significant short- or long-term complications were noted. The functional results of these repairs are equivalent to other, less convenient or technically more difficult methods of reconstruction.


Production of specific copolymers of polyhydroxyalkanoates from industrial waste.
Polyhydroxyalkanoates, biodegradable plastics with the desired physical and chemical properties of conventional synthetic plastics, are extensively investigated. In this study, specific bacterial strains produced specific copolymers from food waste. Copolymers of HB and HV (poly[3-hydroxybutyrate-co-3-hydroxyvalerate]) were obtained using various ratios of butyric acid (C4) and valeric acid (C5) as carbon sources. The C4 to C5 ratio affected the melting points of the copolymers. Melting and glass transition temperatures and many other thermal properties are important parameters relative to in-service polymer applications. Higher ratios of butyrate to valerate gave higher melting points. When a mixed culture of activated sludge was employed to produce copolymers using food wastes as nutrients, the obtained copolymers showed various monomer compositions. Copolymers with a higher portion of HV were obtained using soy waste; copolymers with less HV were obtained using malt wastes. Pure strains, (i.e., Alcaligenes latus DSM 1122, and DSM 1124, Staphylococcus spp., Klebsiella spp.) produced specific copolymers from food waste. Only Klebsiella spp. produced different copolymers; the ratios of HB:HV were 93:7 and 79:21 from malt waste and soy waste, respectively. The other strains produced polymers of 100% HB. Selecting industrial food wastes as carbon sources can further reduce the cost of producing copolymers.


Nuclear RNA surveillance complexes silence HIV-1 transcription.
Expression from the HIV-1 LTR can be repressed in a small population of cells, which contributes to the latent reservoir. The factors mediating this repression have not been clearly elucidated. We have identified a network of nuclear RNA surveillance factors that act as effectors of HIV-1 silencing. RRP6, MTR4, ZCCHC8 and ZFC3H1 physically associate with the HIV-1 TAR region and repress transcriptional output and recruitment of RNAPII to the LTR. Knock-down of these factors in J-Lat cells increased the number of GFP-positive cells, with a concomitant increase in histone marks associated with transcriptional activation. Loss of these factors increased HIV-1 expression from infected PBMCs and led to reactivation of HIV-1 from latently infected PBMCs. These findings identify a network of novel transcriptional repressors that control HIV-1 expression and which could open new avenues for therapeutic intervention.


Encapsulating Peritoneal Sclerosis Presenting after Two Donor Kidney Transplantations: A Case Report and Literature Review.
Encapsulating peritoneal sclerosis is a rare, recurring complication in peritoneal dialysis (PD) patients. With a mortality rate of 51%, it continues to be a therapeutic enigma among clinicians. However, the incidence after kidney transplantation (KT) has rarely been reported. We report a unique case of encapsulating peritoneal sclerosis (EPS), occurring years after failed initial living KT, and diagnosed after second deceased donor kidney transplantation. A 35-year-old male, on prior PD for 4 years, followed by failed KT of 8 years, was presented with abdominal pain, weight loss, and vomiting, 7 months after his second deceased donor KT. An abdominal computed tomography showed intra-abdominal loculated fluid collection, but no obstruction. Exploratory laparotomy revealed extensive peritoneal thickening and blocked intestinal loops. Histopathology was indicative of EPS with fibrous adhesions and sclerotic tissues. Besides restarting his immunosuppressive medications, tamoxifen therapy was initiated as definitive medical management. Currently, he is in clinical remission, follows at transplant clinic, and still experiences episodes of small bowel obstruction. Though the incidence of EPS after KT has been observed sporadically worldwide, none has been reported in the USA. Despite its prevalence in PD patients, therapeutic interventions attempted so far, are not definitive.


[Effects of the implementation of Universal Access with Explicit Guaranties (AUGE) Plan on the quality of care of patients with terminal renal failure].
The implementation of the AUGE plan for renal failure in Chile in August 2002, generated larger waiting list for outpatient care. To analyze the incidence of terminal renal failure, the proportion of patients that were admitted to hemodialysis using a definitive vascular access and the lapse of use of transitory catheters, before and after the implementation of AUGE in Calama. Since 1999, in a dialysis center of Calama, all new patients that are admitted to hemodialysis and the type of vascular access they have are registered. Using this registry, the incidence of terminal renal failure and the lapse between the admission to the center and the installation of a definitive vascular access were calculated for the period 2000 to 2005. From January 2000 to December 2003, the incidence of terminal renal failure was stable in 190 +/- 21 patients per million inhabitants (ppmh). It decreased between January and September 2004 to 124 +/- 18.6. Afterwards, it progressively increased to 221 +/- 21 ppmh. In the study period, the proportion of patients admitted to hemodialysis with a definitive access decreased from 63 to 10% (p<0.01) and the mean lapse of transitory catheter use, increased from 32.9 +/- 42.6 to 73.1 +/- 80.4 days (p<0.01). The implementation of AUGE for chronic renal failure reduced the quality of care of patients admitted to hemodialysis.


Membrane-Active Molecular Machines.
Both biological and artificial membrane transporters mediate passive transmembrane ion flux predominantly via either channel or carrier mechanisms, tightly regulating the transport of materials entering and exiting the cell. One early elegant example unclassifiable as carriers or channels was reported by Smith who derivatized a phospholipid molecule into an anion transporter, facilitating membrane transport via a two-station relay mechanism (Smith et al. J. Am. Chem. Soc. 2008, 130, 17274-17275). Our journey toward blurring or even breaking the boundaries defined by the carrier and channel mechanisms starts in January of 2018 when seeing a child swinging on the swing at the playground park. Since then, I have been wondering whether we could build a nanoscale-sized molecular swing able to perform the swing function at the molecular level to induce transmembrane ion flux. Such research journey culminates in several membrane-active artificial molecular machines, including molecular swings, ion fishers, ion swimmers, rotors, tetrapuses and dodecapuses that permeabilize the membrane via swinging, ion-fishing, swimming, rotating, or swing-relaying actions, respectively. Except for molecular ion swimmers, these unconventional membrane transporters in their most stable states readily span across the entire membrane in a way akin to channels. With built-in flexible arms that can swing or bend in the dynamic membrane environment, they transport ions via constantly changing ion permeation pathways that are more defined than carriers but less defined than channels. Applying the same benzo-crown ether groups as the sole ion-binding and -transporting units, these transporters however differ immensely in ion transport property. While the maximal K+ transport activity is achieved by the molecular swing also termed "motional channel" that displays an EC50 value of 0.021 mol % relative to lipid and transports K+ ions at rate 27% faster than gramicidin A, the highest K+/Na+ selectivity of 18.3 is attained by the molecular ion fisher, with the highest Na+/K+ selectivity of 13.7 by the molecular dodecapus. Having EC50 values of 0.49-1.60 mol % and K+/Na+ values of 1.1-6.3, molecular rotors and tetrapuses are found to be generally active but weakly to moderately K+-selective. For molecular ion swimmers that contain 10 to 14 carbon atom alkyl linkers, they all turn out to be highly active (EC50 = 0.18-0.41 mol %) and highly selective (RK+/RNa+ = 7.0-9.5) transporters. Of special note are crown ether-appended molecular dodecapuses that establish the C60-fullerene core as an excellent platform to allow for a direct translation of solution binding affinity to transmembrane ion transport selectivity, providing a de novo basis for rationally designing artificial ion transporters with high transport selectivity. Considering remarkable cytotoxic activities displayed by molecular swings and ion swimmers, the varied types of existing and emerging unconventional membrane transporters with enhanced activities and selectivities eventually might lead to medical benefits in the future.