A new species of Alopoglossus lizard (Squamata, Alopoglossidae) from the Southern Guiana Shield, northeastern Amazonia, with remarks on diagnostic characters to the genus.
I describe a new species of Alopoglossus from the Southern Guiana Shield in northern Brazilian Amazonia. The new species morphologically resembles A. angulatus in having scales on sides of neck similar in shape to dorsals, nongranular, keeled, and imbricate. Nonetheless, the presence of four pairs of chin shields, with the third pair heptagonal and separated from gulars by large scales, can distinguish the new species from A. angulatus. This description increases the species diversity of the genus Alopoglossus in eastern Amazonia, from where only one taxon was recognized to occur. In addition, I discuss the nomenclature of some diagnostic characters, on the chin region, to the genus, and I present an updated key to Alopoglossus.


Changes in basal hypothalamo-pituitary-adrenal activity during exercise training are centrally mediated.
The effects of exercise training on hypothalamo-pituitary-adrenal (HPA) function are unclear. We investigated whether pituitary-adrenal adaptation during exercise training is mediated by changes in neuropeptide and corticosteroid receptor gene expression in the brain and pituitary. Sprague-Dawley rats were subject to either daily swimming (DS) or sham exercise (SE) for 45 min/day, 5 days/week, for 2 (2W), 4 (4W), or 6 wk (6W) (n = 7-10/group). Corticosterone (Cort) and catecholamine responses during swimming were robust at 6W compared with 2W and 4W, indicating that HPA response to exercise during training is not attenuated when absolute intensity is progressively increased. In DS, basal (morning) plasma ACTH and Cort levels increased from 2W to 4W but plateaued at 6W, whereas in SE, they increased from 4W to 6W, with 6W values higher than in DS. In DS, there was a transient decrease in glucocorticoid receptor (GR) mRNA in the paraventricular nucleus (PVN) and pituitary and a transient increase in corticotrophin-releasing hormone (CRH) mRNA. In contrast, hippocampal mineralocorticoid receptor mRNA and PVN GR mRNA decreased from 4W to 6W in SE, with 6W values lower than in DS. These findings suggest that exercise training prevents an elevation in basal pituitary-adrenal activity potentially via transient alterations in the gene transcription of PVN and pituitary GR as well as CRH to suppress central drive to the HPA axis. In contrast, the increase in basal pituitary-adrenal activity with repeated sham exercise appears to be associated with decreases in hippocampal MR and PVN GR mRNA expression.


Women's access to food-processing technology at the household level is associated with improved diets at the pre-harvest lean season in The Gambia.
Women's access to food processing technology at the household level may have positive dietary benefits during the pre-harvest lean season when households are most stressed from food shortages and higher energy expenditures from agricultural work. This study in rural Gambia was conducted to determine if women's access to small manually operated oil presses (ram) for sesame oil extraction had any significant effects on seasonal fluctuations of household oil supply and on dietary intakes of women and children. Participants were 40 women and children with access to community-based motorized oil press expellers (Expeller-control), 37 women and children with access to village-based ram presses (Press-experiment), and 43 women and children with access to both ram press and motorized expeller (Combination). Dietary data were collected at baseline, at peak oil-pressing, at pre-harvest lean, and at the post-harvest seasons. Households in the Press-experiment and Combination groups consumed 37 and 51 percent more oil, respectively, than those in the Expeller-control group during the pre-harvest lean season. Women from the Press-experiment and Combination groups consumed more energy at the lean season than those in the Expeller-control group. Similarly, children from the Press-experiment and Combination groups consumed more protein at peak oil-processing season than those from the Expeller-control group. At the pre-harvest season children from these two groups also consumed more protein, however, only the consumption of the Combination children was statistically significant compared with that of the Expeller-control group (p < .05). Press-experiment children consumed more nutrient-dense weaning foods during the pre-harvest lean season than Expeller-control children. Women's access to appropriate technology can provide the means to "add value" to their agriculture product, which may serve as an economic stabilizer with potential to increase dietary intakes and incomes, especially during the pre-harvest lean season.


The role of basophil activation test in special populations with mastocytosis and reactions to hymenoptera sting.
Systemic mastocytosis (SM) may be associated with hymenoptera allergy. In such cases, immunotherapy is a life-saving treatment, but a circumstantiated diagnosis is needed for its prescription. Patients with SM and previous reactions to stings, but with negative tests represent a diagnostic dilemma. The basophil activation test (BAT) may be helpful in refining the diagnosis. We assessed the usefulness of BAT in subpopulations of mastocytosis patients, including those with negative tests for insect allergy. Within a population of patients with mastocytosis and previous stings, we studied by BAT and augmented intradermal test (IDT) (10 µg/ml) two groups: (1) with reactions to stings and negative tests; (2) without reactions and negative tests. Basophil activation test was performed with different venoms, assessing at flow cytometry basophils' activation. Sixty-three patients had mastocytosis and 52 had reactions to previous hymenoptera stings. Of them, seven proved negative to diagnostic tests. In six of seven of those patients, BAT was negative with all venoms, and in one, basophils resulted activated also with the negative control. In six patients without previous reactions and negative tests, BAT was totally negative in five of six patients and weakly positive to Hornet in one. Finally, the IDT at 10 µg/ml venom produced nonspecific positive results in most cases. In patients with mastocytosis, the negative results of standard tests are reliable, because BAT and IDT at higher concentration do not add useful information.


N270 sensitivity to conflict strength and working memory: A combined ERP and sLORETA study.
The event-related potential N270 component is known to be an electrophysiological marker of the supramodal conflict processing. However little is know about the factors that may modulate its amplitude. In particular, among all studies that have investigated the N270, little or no control of the conflict strength and of the load in working memory have been done leaving a lack in the understanding of this component. We designed a spatial audiovisual conflict task with simultaneous target and cross-modal distractor to evaluate the N270 sensitivity to the conflict strength (i.e., visual target with auditory distractor or auditory target with visual distractor) and the load in working memory (goal task maintenance with frequent change in the target modality). In a first session, participants had to focus on one modality for the target position to be considered (left-hand or right-hand) while the distractor could be at the same side (compatible) or at opposite side (incompatible). In a second session, we used the same set of stimuli as in the first session with an additional distinct auditory signal that clued the participants to frequently switch between the auditory and the visual targets. We found that (1) reaction times and N270 amplitudes for conflicting situations were larger within the auditory target condition compared to the visual one, (2) the increase in target maintenance effort led to equivalent increase of both reaction times and N270 amplitudes within all conditions and (3) the right dorsolateral prefrontal cortex current density was higher for both conflicting and active maintenance of the target situations. These results provide new evidence that the N270 component is an electrophysiological marker of the supramodal conflict processing that is sensitive to the conflict strength and that conflict processing and active maintenance of the task goal are two functions of a common executive attention system.


eHealth usage among parents to premature or surgically treated neonates: associations with eHealth literacy, healthcare satisfaction or satisfaction with an eHealth device.
A specific eHealth device, a surf tablet, was developed for bridging between advanced in-hospital care and children's homes. Since little is known about determinators for parental eHealth usage, the study's aim was to explore if parents' usage of the device was associated with their eHealth literacy, or their satisfaction with their child's healthcare or with the specific surf tablet. In this explorative usage and questionnaire study, parents to neonates who were discharged home after advanced in-hospital care were included. Their surf tablet usage at maximum 30 days after discharge was reported as frequency (%) of active days (usage days/days having the device) and median number of tablet activities (chat and photo) per usage day. eHealth literacy (eHealth Literacy Questionnaire; eHLQ), healthcare satisfaction (PedsQL Healthcare Satisfaction Generic Module), and satisfaction with the surf tablet were explored regarding tablet usage. Statistics were described in median (range) and (%) using non-parametric and regression models (p < 0.05). Parents to 32 children (11 premature, 21 operated) were included. Active days with eHealth communication using the device was 39% (9.0/29.5), with 2.0 (1.0-4.2) usage occasions per active day. Activity on the tablet was higher among parents reporting to be very satisfied or satisfied with the device (n = 25) compared with neutral/dissatisfied parents (n = 7) (2.8 vs. 2.2 vs. 1.6 activities) (p = 0.030), while their frequency of active days did not differ (31.6% vs. 38.3% vs. 40%) (p = 0.963). A higher eHealth literacy was not associated with frequency of active days (0.926 (0.652-1.317); p = 0.659) or number of eHealth activities (0.973 (0.758-1.250); p = 0.825). Healthcare satisfaction was not associated with higher frequency of active days 0.996 (0.983-1.009; p = 0.519); neither was number of eHealth activities 1.001 (0.991-1.011; p = 0.883). In this study, eHealth usage was associated with parental satisfaction with the specific eHealth device, but not with eHealth literacy or healthcare satisfaction. To assure equal access to healthcare when using eHealth, the user-friendliness of the device seems to be crucial, and technical support needs to be in place. NCT04150120 (04/11/2019).


KCMBT: a k-mer Counter based on Multiple Burst Trees.
A massive number of bioinformatics applications require counting of k-length substrings in genetically important long strings. A k-mer counter generates the frequencies of each k-length substring in genome sequences. Genome assembly, repeat detection, multiple sequence alignment, error detection and many other related applications use a k-mer counter as a building block. Very fast and efficient algorithms are necessary to count k-mers in large data sets to be useful in such applications. We propose a novel trie-based algorithm for this k-mer counting problem. We compare our devised algorithm k-mer Counter based on Multiple Burst Trees (KCMBT) with available all well-known algorithms. Our experimental results show that KCMBT is around 30% faster than the previous best-performing algorithm KMC2 for human genome dataset. As another example, our algorithm is around six times faster than Jellyfish2. Overall, KCMBT is 20-30% faster than KMC2 on five benchmark data sets when both the algorithms were run using multiple threads. KCMBT is freely available on GitHub: (https://github.com/abdullah009/kcmbt_mt). firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


A single genetic locus lengthens deer mouse burrows via motor pattern evolution.
The question of how evolution builds complex behaviors has long fascinated biologists. To address this question from a genetic perspective, we capitalize on variation in innate burrowing behavior between two sister species of Peromyscus mice: P. maniculatus that construct short, simple burrows and P. polionotus that uniquely construct long, elaborate burrows. We identify three regions of the genome associated with differences in burrow length and then narrow in on one large-effect 12-Mb locus on chromosome 4. By introgressing the P. polionotus allele into a P. maniculatus background, we demonstrate this locus, on its own, increases burrow length by 20%. Next, by recording mice digging in a transparent tube, we find this locus has specific effects on burrowing behavior. This locus does not affect time spent digging or latency to dig, but rather affects usage of only two of the primary digging behaviors that differ between the focal species: forelimb digging, which loosens substrate, and hindlimb kicking, which powerfully ejects substrate. This locus has an especially large effect on hindkicking, explaining 56% and 22% of interspecific differences in latency and proportion of hindkicks, respectively. Together, these data provide genetic support for the hierarchical organization of complex behaviors, offering evolution the opportunity to tinker with specific behavioral components.


Socioeconomic factors and heavy drinking over the course of the week among job seekers with at-risk alcohol use.
This article investigates the influence of socioeconomic factors on heavy drinking over the course of the week. As part of a randomized controlled trial, 1,282 job seekers with at-risk alcohol use were systematically recruited at 3 job agencies and reported number of drinks consumed on each day in the past week. Latent growth curve models were calculated to represent variations of alcohol use. School education and duration of lifetime unemployment were tested as predictors; sociodemographic variables were integrated as covariates. A weekly pattern was confirmed in the total sample: constant low alcohol use on working days, escalation on Friday, and a further increase on weekends. Significant associations between longer duration of lifetime unemployment and higher initial alcohol use on Sundays (p < .001) and less increase on Fridays (p = .001) disappeared after controlling for sociodemographic factors. Longer duration of lifetime unemployment does not appear to affect alcohol use trajectories over the course of the week.


The complete mitochondrial genome of the Neochauliodes fraternus (Megaloptera: Corydalidae).
The mitochondrial genome of Neochauliodes fraternus (Megaloptera: Corydalidae) is a circular molecule of 15,768 bp in length, containing 37 typical mitochondrial genes: 13 protein-coding genes (PCGs), 2 ribosomal RNAs, 22 transfer RNAs and a non-coding AT-rich region. Its gene order and arrangement are identical to the common type found in most insect mitogenomes. All PCGs start with a typical ATN codon except for the ND1 which uses TTG as its start codon; all PCGs terminate in the common stop codon TAA or TAG, except for the COI, COIII, ND3, ND5, ND4 and CYTB which use single T as their stop codons. The non-coding AT-rich region is 1031 bp long, located between rrnS and tRNA(lle) genes. It contains some structures of repeated motifs and microsatellite-like elements characteristic of the megaloptera.


Desorption properties of the R600, R134a and their mixtures in several MOF structures: A molecular dynamics study.
The efficiency of organic Rankine cycle is expected to be enhanced via using metal organic heat carriers. Thus, it is important to investigate the properties of organic working fluid in metal organic frameworks (MOFs). In this paper, molecular dynamics method was employed to study the desorption properties of R600, R134a, and their mixtures in MOF-5, IRMOF-16, and MOF-200 structures. The results show that the desorption capacity of pure working fluids are negatively correlated with their molecular size. In mixed refrigerant systems, the desorption of the working medium is competitive, and the higher the proportion of fluorine atoms in the system, the greater the desorption heat in IRMOF-16. It is noteworthy that the behavior of the desorption heat in the other two MOFs is diametrically opposed to this result. The desorption capacity is positively correlated with the average pore size, specific surface area, and porosity of the MOF. The self-diffusion coefficient of the working medium in MOF is inversely proportional to its molecular weight, but directly proportional to its molecular size and to the pore size of MOF.


An unusual case of swelling--Clarkson's syndrome.
Clarkson's syndrome, also called idiopathic systemic capillary leak syndrome is a rare condition characterised by vascular hyper permeability resulting in extreme intravascular volume depletion. The syndrome is unique and almost paradoxical in its presentation, with findings initially suggesting overwhelming heart failure, but in reality the extra vascular fluid represents overt capillary leak, with ultimate intravascular volume depletion, a low output state and hypovolemic shock. Previously described characteristics have classically included severe oedema and anasarca with rapid, profound shock, typically accompanied by haemoconcentration. The authors describe a patient, initially seeming benign in presentation, who rapidly progressed with confusing findings of fluid overload by examination and imaging, ultimately manifesting these findings by severe capillary leak rather than hydrostatic oedema, with ultimate hypovolaemic shock, multisystem organ failure and death. Our aim is that by describing clinical, haemodynamic and pathologic descriptors of the disease, the authors can aid in increasing physician awareness of this unusual syndrome.


Cross-species homology of the CLN3 gene.
A murine cDNA clone was isolated by screening a mouse cDNA library with the human CLN3 cDNA. Sequence analysis indicates that the corresponding CLN3 proteins are highly homologous. We have compared these with recently identified CLN3 sequences from the dog, the nematode C. elegans, and baker's yeast S. cerevisiae. The CLN3 protein is remarkably conserved across eukaryotic species. Several protein modification sites which may be crucial for the function of the protein are conserved.


[Community structure and distribution pattern of small mammals in agricultural area of Yunnan Province, China.]
To understand the characteristics of community structure and spatial distribution of small mammals in agricultural area of Yunnan Province, a systematic investigation was carried out in 104 quadrats of 25 regions in Yunnan Province from August 2010 to April 2018 by rat trap night method. The spatial variation of community characteristics along environmental gradients was analyzed by community ecological indicators. The results showed that a total of 3240 small mammals were captured and cold be classified into 42 species in 21 genera, 9 families, and 4 orders. The largest number of small mammal was rodents, dominated by Apodemus chevrieri and Rattus tanezumi. The 25 regions were clustered into three classes. The altitudinal distribution of small mammals was similar to the latitudinal distribution in agricultural areas. The number of species was relatively less in the low latitude and altitude range, with Rattus spp. and Mus spp. as the dominant species. In the high latitude and altitude region, the dominant species changed into Apodemus, Niviventer and Eothenomys. With the increases of altitude, the diversity index showed unimodal distribution, with the highe-st species diversity occurred in the mid-altitude area. The diversity index of small mammal showed the "V" type pattern in longitude, being the highest in the 98°-99° E gra-dient zone. At the latitude level, it showed an overall upward trend from south to north. Results from the GAM analysis showed that the degree of influence on the small animals in the agricultural area was in order of longitude, altitude and latitude. The similarity analysis in the composition of small mammals showed that the moderate similarity occurred in the adjacent gradient zone, and the highest similarity occurred in middle altitude zone, middle latitude zone, and low longitude zone. The farther the distance between different gradient zones, the lower the similarity of community structure. There was high spatial heterogeneity in different dimensions of small mammals' community structure in Yunnan Province. The geographical distribution trend of species diversity showed different distribution patterns across environmental gradients.


Clinicopathological characteristics, treatments, and prognosis of breast ductal carcinoma in situ with microinvasion: A narrative review.
Ductal carcinoma in situ with microinvasion (DCIS-MI) is defined as ductal carcinoma in situ (DCIS) with a microscopic invasive focus ≤1 mm in the longest diameter. The current literature is controversial concerning the clinical prognostic features and management of DCIS-MI. This narrative review described recently reported literature regarding the characteristics, treatment, and prognosis of it. Searching PubMed for relevant articles covering the period of 1982 to 2021 using the following terms by MeSH and free-word: breast cancer, microinvasion, DCIS, DCIS-MI, and invasive ductal carcinoma (IDC). DCIS-MI tends to express more aggressive pathological features such as necrosis, HER2+, ER- or PR-, and high nuclear grade. The overall prognosis of DCIS-MI is typically good, however, some indicators such as young age, HR-, HER2+ and multimicroinvasive lesions, were associated with worse prognoses. And there are also conflicting results on the differences between the prognoses of DCIS-MI and DCIS or T1a-IDC. Postoperative chemotherapy and anti-HER2 therapy still have uncertain benefits and are more likely to be used to treat high-risk patients who are HR- orHER2+ to improve the prognosis. DCIS-MI has more aggressive pathological features, which may suggest its biological behavior is worse than that of DCIS and similar to early IDC. Although the overall prognosis of DCIS-MI is good, when making decisions about adjuvant therapy clinicians need to give priority to the hormone receptor status, HER2 expression and axillary lymph node status of patients, because these may affect the prognosis and treatment response.


Early intervention in panic: randomized controlled trial and cost-effectiveness analysis.
Panic disorder (PD) is a common, severe and persistent mental disorder, associated with a high degree of distress and occupational and social disability. A substantial proportion of the population experiences subthreshold and mild PD and is at risk of developing a chronic PD. A promising intervention, aimed at preventing panic disorder onset and reducing panic symptoms, is the 'Don't Panic' course. It consists of eight sessions of two hours each. The purpose of this study is to evaluate the effectiveness of this early intervention - based on cognitive behavioural principles - on the reduction of panic disorder symptomatology. We predict that the experimental condition show superior clinical and economic outcomes relative to a waitlisted control group. A pragmatic, pre-post, two-group, multi-site, randomized controlled trial of the intervention will be conducted with a naturalistic follow-up at six months in the intervention group. The participants are recruited from the general population and are randomized to the intervention or a waitlist control group. The intervention is offered by community mental health centres. Included are people over 18 years of age with subthreshold or mild panic disorder, defined as having symptoms of PD falling below the cut-off of 13 on the Panic Disorder Severity Scale-Self Report (PDSS-SR). Primary outcomes are panic disorder and panic symptoms. Secondary outcomes are symptoms of agoraphobia, anxiety, cognitive aspects of panic disorder, depressive symptoms, mastery, health-related quality of life, and cost-effectiveness. We will examine the following variables as potential mediators: cognitive aspects of panic disorder, symptoms of agoraphobia, anxiety and mastery. Potential moderating variables are: socio-demographic characteristics, panic disorder, agoraphobia, treatment credibility and mastery. This study was designed to evaluate the (cost) effectiveness of an early intervention based on cognitive behavioural principles. The strong external validity is one of the strengths of the study design. Current Controlled Trials ISRCTN33407455.


Prothymosin alpha associates with the oncoprotein SET and is involved in chromatin decondensation.
Prothymosin alpha (ProTalpha) is a histone H1-binding protein that interacts with the transcription coactivator CREB-binding protein and potentiates transcription. Based on coimmunoprecipitation and mammalian two-hybrid assays, we show here that ProTalpha forms a complex with the oncoprotein SET. ProTalpha efficiently decondenses human sperm chromatin, while overexpression of GFP-ProTalpha in mammalian cells results in global chromatin decondensation. These results indicate that decondensation of compacted chromatin fibers is an important step in the mechanism of ProTalpha function.


The Glymphatic System: a Potential Key Player in Bacterial Meningitis.
The glial-lymphatic system (glymphatic system) is a recently characterized fluid clearance pathway of the central nervous system. Glymphatic system disfunctions leading to defects in drainage of the cerebrospinal fluid have been associated with several neurological disorders. In their article, J. S. Generoso, S. Thorsdottir, A. Collodel, R. R. E. Santo, et al. (mBio 13:e01886-22, 2022, https://doi.org/10.1128/mBio.01886-22) have now associated impaired glymphatic system functionality to neurological sequelae of murine meningitis caused by Streptococcus pneumoniae. Their work provides an initial and important step into the systematic evaluation of a potential impact of glymphatic system functionality on disease severity and sequelae in meningitis.


PSA-NCAM immunoreactivity in chandelier cell axon terminals of the human temporal cortex.
In the adult central nervous system, the expression of polysialylated forms of the cell-surface glycoprotein NCAM (PSA-NCAM) is thought to be confined to areas particularly susceptible to plastic changes. In the present study, PSA-NCAM was found to be expressed in the somata, dendrites and axonal processes of some neurons, including cartridge-like elements, which according to our criteria, were identified as chandelier cell axon terminals (chandelier terminals), in the adult human entorhinal cortex and neocortex. These chandelier terminals were very numerous in layers II and III, whereas in deeper layers they were found only occasionally. Double immunocytochemical staining for PSA-NCAM with parvalbumin (PV), with GABA transporter (GAT-1) or with the 5-HT(1A) serotonin receptor allowed us to verify them as true chandelier terminals. Nearly all (92-95%) PV-immunoreactive (-ir) and GAT-1-ir chandelier terminals in layers II and III coexpressed PSA-NCAM. Most of the PSA-NCAM-ir chandelier terminals (89-98%) were also labeled for PV and GAT-1. The results suggest that chandelier terminals in layers II and III of the human entorhinal cortex and temporal neocortex might be particularly susceptible to plastic changes.


Alanine and sodium fluxes across mucosal border of rabbit ileum.
Unidirectional influxes of L-alanine and Na from the mucosal solution into the epithelium of in vitro rabbit ileum have been determined. In the presence of 140 mM Na, alanine influx is approximately 2.2 micromoles/hr cm(2), but is inhibited if the NaCl in the mucosal solution is replaced by choline Cl, Tris-Cl, mannitol, LiCl, or KCl. Although alanine influx is strongly dependent upon Na in the mucosal solution, it is uninfluenced by marked reduction of intracellular Na pools. In addition, alanine influx is unaffected by intracellular alanine concentration. Na influx is markedly inhibited by the presence of Li. Evidence is presented that Na transport across the mucosal border cannot be attributed to simple diffusion even though the net flux across this surface is in the direction of the electrochemical potential difference.


Machine learning and image analysis in vascular surgery.
Deep learning, a subset of machine learning within artificial intelligence, has been successful in medical image analysis in vascular surgery. Unlike traditional computer-based segmentation methods that manually extract features from input images, deep learning methods learn image features and classify data without making prior assumptions. Convolutional neural networks, the main type of deep learning for computer vision processing, are neural networks with multilevel architecture and weighted connections between nodes that can "auto-learn" through repeated exposure to training data without manual input or supervision. These networks have numerous applications in vascular surgery imaging analysis, particularly in disease classification, object identification, semantic segmentation, and instance segmentation. The purpose of this review article was to review the relevant concepts of machine learning image analysis and its application to the field of vascular surgery.


Cardiomyoblast caveolin expression: Effects of simulated diabetes, α-linolenic acid and cell signaling pathways.
Caveolins regulate myocardial substrate handling, survival signaling and stress-resistance, however control of expression is incompletely defined. We test how metabolic features of type 2 diabetes (T2D), and modulation of cell signaling, influence caveolins in H9c2 cardiomyoblasts. Cells were exposed to glucose (25 vs. 5 mM), insulin (100 nM) or palmitate (0.1 mM), individually or combined, and effects of adenylate cyclase (AC) activation (50 μM forskolin), focal adhesion kinase (FAK) or protein kinase C b2 (PKCβ2) inhibition (1 μM FAK Inhibitor 14 or CGP-53353, respectively), or the polyunsaturated fatty acid (PUFA) α-linolenic acid (ALA; 10 μM) were tested. Simulated T2D (elevated glucose+insulin+palmitate) depressed caveolin-1 and -3 without modifying caveolin-2. Caveolin-3 repression was primarily palmitate dependent, whereas high glucose (HG) and insulin independently increased caveolin-3 (yet reduced expression when combined). Differential control was evident: baseline caveolin-3 was suppressed by FAK/PKCβ2 and insensitive to AC activities, with baseline caveolin-1 and -2 suppressed by AC and insensitive to FAK/PKCβ2. Forskolin and ALA selectively preserved caveolin-3 in T2D cells, whereas PKCb2 and FAK inhibition increased caveolin-3 under all conditions. Despite preservation of caveolin-3, ALA did not modify nucleosome content (apoptosis marker) or transcription of pro-inflammatory mediators in T2D cells. In summary: caveolin-1 and -3 are strongly repressed with simulated T2D, with caveolin-3 particularly sensitive to palmitate; intrinsic PKCb2 and FAK activities repress caveolin-3 in healthy and stressed cells; ALA, AC activation and PKCβ2 inhibition preserve caveolin-3 under T2D conditions; and caveolin-3 changes with T2D and ALA appear unrelated to inflammatory signaling and extent of apoptosis.


Chiral cardiovascular drugs: an overview.
Stereochemistry in drug molecules is rapidly becoming an important aspect in drug research, design, and development. Recently, individual stereoisomers of drug molecules with asymmetric centers such as fexofenadine, cetirizine, verapamil, fluoxetine, levalbutarol, and amphetamine, for example, have been separated and developed as individual drugs. These stereoisomers have different therapeutic activity, and each isomer has contributed differently with respect to its formulation's pharmacologic activity, side effects, and toxicity. The present overview discusses chirality among a select group of cardiovascular drugs, their stereochemical synthesis/preparation, isolation techniques using chiral chromatography, methods for confirmation of their enantiomeric purity, pharmacodynamics, and pharmacokinetics. Chirality has been visualized as an important factor in cardiovascular research. It is also becoming evident in other areas of therapeutics.


[Medical pluralism revealed by private correspondence in XVIII century Catalonia].
This work constitutes an approach to the complex world of medical pluralism during the modern age. First, there is a review of the recent historiography concerned with recovering all the possible medical resources that existed and were offered to the patient. The complexity of this medical world are then described, noting the persistence of some elements throughout the late medieval and early modern period. Within the theoretical framework and historical setting established, the work concludes by showing the complexity and permanent interrelationship in the care options, from the point of view of private correspondence of the Veciana family at the end of the XVIII century.


Prospect of phytoaccumulation of arsenic by Brassica juncea (L.) in Bangladesh.
The phytoaccummulation of arsenic by Brassica juncea (L.) was investigated for varying concentrations selected within the range that is evident in Bangladeshi soil. B. juncea (Rai and BARI-11) was grown in the hydroponic media under greenhouse condition with different concentrations (0.5, 1.0, 15, 30, 50 and 100 ppm) of sodium arsenite. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used to analyze the data. Mapping of potential area of phytoaccumulation of arsenic by B. juncea was done using Geographic information system (GIS). Arsenic was detected at lower concentrations (0.5 and 1.0 ppm) only at root system of the plant. For higher concentrations (15, 30, and 50 ppm) arsenic was detected both in the root and shoot systems. The results suggested that at 15 and 50 ppm uptake was higher compared to 30 ppm. For 100 ppm of arsenic no plant growth was observed. In Bangladesh, where concentration of arsenic is at lower level and present only at rooting zone, B. juncea may be used for phytoaccumulation of arsenic keeping usual agronomic practices. However, for higher concentrations, B. juncea can be regarded as a good accumulator of arsenic where uptake of arsenic was up to 1% of total biomass of the plant.


Biology of GD2 ganglioside: implications for cancer immunotherapy.
Part of the broader glycosphingolipid family, gangliosides are composed of a ceramide bound to a sialic acid-containing glycan chain, and locate at the plasma membrane. Gangliosides are produced through sequential steps of glycosylation and sialylation. This diversity of composition is reflected in differences in expression patterns and functions of the various gangliosides. Ganglioside GD2 designates different subspecies following a basic structure containing three carbohydrate residues and two sialic acids. GD2 expression, usually restrained to limited tissues, is frequently altered in various neuroectoderm-derived cancers. While GD2 is of evident interest, its glycolipid nature has rendered research challenging. Physiological GD2 expression has been linked to developmental processes. Passing this stage, varying levels of GD2, physiologically expressed mainly in the central nervous system, affect composition and formation of membrane microdomains involved in surface receptor signaling. Overexpressed in cancer, GD2 has been shown to enhance cell survival and invasion. Furthermore, binding of antibodies leads to immune-independent cell death mechanisms. In addition, GD2 contributes to T-cell dysfunction, and functions as an immune checkpoint. Given the cancer-associated functions, GD2 has been a source of interest for immunotherapy. As a potential biomarker, methods are being developed to quantify GD2 from patients' samples. In addition, various therapeutic strategies are tested. Based on initial success with antibodies, derivates such as bispecific antibodies and immunocytokines have been developed, engaging patient immune system. Cytotoxic effectors or payloads may be redirected based on anti-GD2 antibodies. Finally, vaccines can be used to mount an immune response in patients. We review here the pertinent biological information on GD2 which may be of use for optimizing current immunotherapeutic strategies.


The relationship between prenatal exposure to organophosphate insecticides and neurodevelopmental integrity of infants at 5-weeks of age.
Organophosphate (OP) insecticides are among the most abundantly used insecticides worldwide. Thailand ranked third among 15 Asian countries in its use of pesticides per unit hectare and fourth in annual pesticide use. More than 40% of Thai women of childbearing age work on farms where pesticides are applied. Thus, the potential for pregnant women and their fetuses to be exposed to pesticides is significant. This study investigated the relationship between early, mid, and late pregnancy maternal urine concentrations of OP metabolites and infant neural integrity at 5 weeks of age. We enrolled women employed on farms from two antenatal clinics in the Chiang Mai province of northern Thailand. We collected urine samples monthly during pregnancy, composited them by early, mid and late pregnancy and analyzed the composited samples for dialkylphosphate (DAP) metabolites of OP insecticides. At 5 weeks after birth, nurses certified in use of the NICU Network Neurobehavioral Scale (NNNS) completed the evaluation of 320 healthy infants. We employed generalized linear regression, logistic and Poisson models to determine the association between NNNS outcomes and DAP concentrations. All analyses were adjusted for confounders and included creatinine as an independent variable. We did not observe trimester specific associations between DAP concentrations and NNNS outcomes. Instead, we observed statistically significant inverse associations between NNNS arousal (β = -0.10; CI: -0.17, -0.002; p = 0.0091) and excitability [0.79 (0.68, 0.92; p = 0.0026)] among participants with higher average prenatal DAP concentrations across pregnancy. We identified 3 NNNS profiles by latent profile analysis. Higher prenatal maternal DAP concentrations were associated with higher odds of being classified in a profile indicative of greater self-regulation and attention, but arousal and excitability scores below the 50th percentile relative to US normative samples [OR = 1.47 (CI: 1.05, 2.06; p = 0.03)]. Similar findings are also observed among infants with prenatal exposure to substances of abuse (e.g., methamphetamine). Overall, the associations between prenatal DAP concentrations and NNNS summary scores were not significant. Further evaluations are warranted to determine the implications of low arousal and excitability for neurodevelopmental outcomes of attention and memory and whether these results are transitory or imply inadequate responsivity to stimulation among children as they develop.


Correlations among handedness, eyedness, monocular shifts from binocular focal point, and nonverbal intelligence in university mathematics students.
Relationships among hand preference, nonverbal intelligence, and the monocular shifts of binocular focal point were studied in 33 men and 12 women university mathematics students. Ocular dominance was assessed with the Miles test. The monocular shift of binocular focal point for each eye was assessed with a modified Miles test. Hand preference was assessed on the Edinburg Handedness Inventory. Nonverbal intelligence was assessed with Cattell's Culture Fair Intelligence Test. In a prior study, the percentage of left-eye preference had been reported to be greater for mathematics students than for nonmathematics students. In the present study there were positive correlations between hand preference and the sum of the monocular shifts of two eyes. In addition, there was a negative correlation between nonverbal intelligence and the sum of the monocular shifts of two eyes. As these resultssuggest that the sum of the monocular shifts of two eyes may be related to mathematical ability and nonverbal intelligence, further research with a larger sample including non-mathematics students is needed.


[Studies on the shift of cefmetazole into the gastrointestinal tract (author's transl)].
From the studies on the stability of cefmetazole and cefazolin in feces of animals and children, and the determination of the fecal concentration of cefmetazole in three pediatric patients, the following results were obtained. 1) When cefmetazole was kept at 37 degrees C for 24 approximately 48 hours in feces of rats, rabbits, dogs and children, it showed no decrease of the potency. On the other hand, cefazolin kept in the same condition as that of cefmetazole showed a remarkable decrease of the potency. 2) Fecal excretions of cefmetazole were 0, 0.22 and 0.65% of total doses, respectively, in two pediatric patients of scarlet fever and one pediatric patient of serous meningitis.


Four free parameter empirical parametrization of glow discharge Langmuir probe data.
For the purpose of developing a simple empirical model capable of producing the electron energy distribution function (EEDF) from Langmuir probe I-V characteristics, a four parameter empirical equation that fits most Langmuir probe experimental data is suggested. The four free fitting parameters are related to the main plasma properties. These properties include the ion and electron saturation currents and the plasma electron temperature. This equation can be readily differentiated twice to give the EEDF according to the Druyvesteyn formula. Furthermore, a MATLAB platform based computer code based on this model yielding results for the plasma potential and all plasma parameters mentioned above is presented. The information given below can be used to write other computer codes for the same purpose in any other programming language.


A case of vascular leiomyoma of the larynx.
We present a 68-year-old woman with a vascular leiomyoma of the larynx, a benign tumour that rarely involves that organ. Chief complaints were a feeling of a narrowing of the pharynx and difficulty in breathing in the supine position. A spherical tumour measuring 1.5 cm and covered with normal mucosa was found at the margin of her epiglottis. The patient was administered a general anaesthetic and the tumour was successfully removed via direct laryngoscopy. Histological examination revealed that the tumour lay beneath a layer of stratified squamous epithelium and was encased in a well-defined fibrous capsule. The tumour parenchyma was composed of proliferated fibres that consisted of elongated cells, surrounded by an abundance of blood vessels. Its complete removal is the treatment of choice with care taken to avoid profuse bleeding. Recurrence is rare.


Abnormal RNA metabolism in spinal motor neurons in the wobbler mouse.
RNA metabolism was studied in anterior horn neurons in wobbler mice. In the wobbler mice, RNA content was reduced in histologically normal neurons but not consistently reduced in vacuolated neurons, as compared with normal littermates. Nuclear and nucleolar incorporation of [5--3H]uridine was reduced both in vacuolated and in histologically normal neurons of wobbler mice, while cytoplasmic counts were higher in histologically normal neurons of wobbler mice than in vacuolated neurons or the neurons of normal littermates. These findings point to an abnormality of RNA synthesis which precedes the earliest morphological changes seen in nerve cells with the light microscope. Nuclear [5--3H]uridine uptake was reduced both in small and in large neurons, a finding suggesting that the metabolic abnormality is probably not confined to alpha-motoneurons.


Enzyme-Mediated Intercellular Proximity Labeling for Detecting Cell-Cell Interactions.
Cell-cell interactions and communications play fundamental roles in life processes but remain largely uncharacterized. We developed an enzyme-mediated proximity cell labeling (EXCELL) strategy as a general method to detect and record cell-cell interactions under living conditions. EXCELL relies on an evolved Staphylococcus aureus transpeptidase sortase A variant (mgSrtA) capable of promiscuous labeling of various cell surface proteins containing a monoglycine residue at the N-terminus. Displaying mgSrtA on the surface of a cell of interest allows the labeling and detection of interacting cells in a proximity-dependent fashion.


Are prophylactic systemic antibiotics necessary with nasal packing? A systematic review.
The use of prophylactic systemic antibiotics with nasal packing has been a controversial topic. There are few evidence-based studies to determine the need for prophylactic systemic antibiotics. We performed a systematic literature review to determine the role of prophylactic systemic antibiotics with nasal packing in the prevention of toxic shock syndrome and local nasal infections. The purpose of this study was to perform a systematic literature review to determine the role of prophylactic systemic antibiotics with nasal packing in the prevention of toxic shock syndrome and local nasal infections. A search for studies that reviewed the efficacy of prophylactic systemic antibiotics in the prevention of toxic shock or nasal infections and/or sinusitis for patients with nasal packing for epistaxis and postoperative septoplasties was performed. This was conducted in a number of medical literature data bases by following the methods of the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only English publications and human studies that were randomized control trials, quasi-randomized control trials, controlled clinical trials, retrospective studies, and case series were included. Six studies, with a total of 990 patients, met the inclusion criteria for the review and were included. Primary outcomes were signs and symptoms of nasal or sinus infections in patients who underwent nasal packing for epistaxis or septoplasty. There were no reports of toxic shock syndrome in any patients, and there was no statistical difference in purulent drainage in patients who had septoplasty (9.9 versus 11.2%) treated with or without antibiotics. There is a paucity of literature that reviewed the need for prophylactic systemic antibiotics with nasal packing. The available literature does not show a significant benefit to the use of antibiotics with nasal packing, but the studies were underpowered to detect such a difference. One must consider the associated risks of prophylactic antibiotics to the patient as well when deciding to prescribe prophylactic antibiotics.


Quantum theory of multiscale coarse-graining.
Coarse-grained (CG) models serve as a powerful tool to simulate molecular systems at much longer temporal and spatial scales. Previously, CG models and methods have been built upon classical statistical mechanics. The present paper develops a theory and numerical methodology for coarse-graining in quantum statistical mechanics, by generalizing the multiscale coarse-graining (MS-CG) method to quantum Boltzmann statistics. A rigorous derivation of the sufficient thermodynamic consistency condition is first presented via imaginary time Feynman path integrals. It identifies the optimal choice of CG action functional and effective quantum CG (qCG) force field to generate a quantum MS-CG (qMS-CG) description of the equilibrium system that is consistent with the quantum fine-grained model projected onto the CG variables. A variational principle then provides a class of algorithms for optimally approximating the qMS-CG force fields. Specifically, a variational method based on force matching, which was also adopted in the classical MS-CG theory, is generalized to quantum Boltzmann statistics. The qMS-CG numerical algorithms and practical issues in implementing this variational minimization procedure are also discussed. Then, two numerical examples are presented to demonstrate the method. Finally, as an alternative strategy, a quasi-classical approximation for the thermal density matrix expressed in the CG variables is derived. This approach provides an interesting physical picture for coarse-graining in quantum Boltzmann statistical mechanics in which the consistency with the quantum particle delocalization is obviously manifest, and it opens up an avenue for using path integral centroid-based effective classical force fields in a coarse-graining methodology.


Recombinant HMGB1 with cytokine-stimulating activity.
We describe methods for the isolation, purification, and characterization of full-length high-mobility group box 1 (HMGB1) and truncated mutants expressed in bacteria and in mammalian Chinese Hamster Ovary (CHO) cells. HMGB1 is an abundant nuclear and cytoplasmic protein, highly conserved across species and widely distributed in eukaryotic cells from yeast to man. As a ubiquitous nuclear DNA binding protein, HMGB1 binds DNA, facilitates gene transcription, and stabilizes nucleosome structure. In addition to these intracellular roles, HMGB1 can be released into the extracellular milieu by activated innate immune cells (i.e., macrophages, monocytes) and functions as a mediator of lethal endotoxemia and sepsis. The proinflammatory cytokine activity of HMGB1 has become an intense area of research and recombinant protein can be a useful tool to probe HMGB1 functions. Due to its dipolar charged properties, HMGB1 isolated by some methods can be contaminated with bacterial products (such as CpG DNA or lipopolysaccharide [LPS]) that may interfere with immunological analyses. Here we report our newly developed methods for the isolation and purification of biologically active HMGB1 from bacteria or mammalian CHO cells that is essentially free of contaminants. This strategy provides an important advance in methodology to facilitate future HMGB1 studies.


Pharmacokinetic stereoselectivity of troglitazone, an antidiabetic agent, in the KK mouse.
Troglitazone, an oral antidiabetic agent, is an equal mixture of four stereoisomers involving two asymmetric centres. In the present study, the stereoselectivity of in vitro epimerization in plasma and organ homogenate and in vivo plasma disposition in the KK mouse, an animal model of non-insulin-dependent diabetes, was examined. In the incubation experiments at 37 degrees C, there was a fivefold to eightfold acceleration of epimerization at the 5 position of the thiazolidine ring in KK mouse plasma compared with that in buffer. However, no inversion at the 2 position of the chroman ring was observed. In addition, there was an approximately 1.3-fold difference in the epimerization rates among stereoisomers at the 2 position of the chroman ring. However, there were no differences in the values of the equilibrium constants of epimerization, and the ratio of epimerization among stereoisomers at the 5 position of thiazolidine ring was almost unity. The acceleration of epimerization is thought to be due to the high degree of protein binding because of the relationship between the initial epimerization rate and the dilution ratio of the plasma. Although acceleration of epimerization was also observed in the 20% homogenates of liver, kidney, and intestine of the KK mouse, the degree of stereoselectivity was lower than in plasma. The analysis of the plasma disposition after intravenous administration of troglitazone stereoisomers, using a kinetic model, indicated that the metabolic clearance in the liver showed a 2.5-fold maximum difference among stereoisomers and that the stereoselectivity of epimerization was low.


OpenFLUX2: (13)C-MFA modeling software package adjusted for the comprehensive analysis of single and parallel labeling experiments.
Steady-state (13)C-based metabolic flux analysis ((13)C-MFA) is the most powerful method available for the quantification of intracellular fluxes. These analyses include concertedly linked experimental and computational stages: (i) assuming the metabolic model and optimizing the experimental design; (ii) feeding the investigated organism using a chosen (13)C-labeled substrate (tracer); (iii) measuring the extracellular effluxes and detecting the (13)C-patterns of intracellular metabolites; and (iv) computing flux parameters that minimize the differences between observed and simulated measurements, followed by evaluating flux statistics. In its early stages, (13)C-MFA was performed on the basis of data obtained in a single labeling experiment (SLE) followed by exploiting the developed high-performance computational software. Recently, the advantages of parallel labeling experiments (PLEs), where several LEs are conducted under the conditions differing only by the tracer(s) choice, were demonstrated, particularly with regard to improving flux precision due to the synergy of complementary information. The availability of an open-source software adjusted for PLE-based (13)C-MFA is an important factor for PLE implementation. The open-source software OpenFLUX, initially developed for the analysis of SLEs, was extended for the computation of PLE data. Using the OpenFLUX2, in silico simulation confirmed that flux precision is improved when (13)C-MFA is implemented by fitting PLE data to the common model compared with SLE-based analysis. Efficient flux resolution could be achieved in the PLE-mediated analysis when the choice of tracer was based on an experimental design computed to minimize the flux variances from different parts of the metabolic network. The analysis provided by OpenFLUX2 mainly includes (i) the optimization of the experimental design, (ii) the computation of the flux parameters from LEs data, (iii) goodness-of-fit testing of the model's adequacy, (iv) drawing conclusions concerning the identifiability of fluxes and construction of a contribution matrix reflecting the relative contribution of the measurement variances to the flux variances, and (v) precise determination of flux confidence intervals using a fine-tunable and convergence-controlled Monte Carlo-based method. The developed open-source OpenFLUX2 provides a friendly software environment that facilitates beginners and existing OpenFLUX users to implement LEs for steady-state (13)C-MFA including experimental design, quantitative evaluation of flux parameters and statistics.


The Short Isoform of DNAJB6 Protects against 1-Methyl-4-phenylpridinium Ion-Induced Apoptosis in LN18 Cells via Inhibiting Both ROS Formation and Mitochondrial Membrane Potential Loss.
In a previous study, we found that the short isoform of DNAJB6 (DNAJB6(S)) had been decreased in the striatum of a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). DNAJB6, one of the heat shock proteins, has been implicated in the pathogenesis of PD. In this study, we explored the cytoprotective effect of DNAJB6(S) against 1-methyl-4-phenylpyridinium ion- (MPP+-) induced apoptosis and the underlying molecular mechanisms in cultured LN18 cells from astrocytic tumors. We observed that MPP+ significantly reduced the cell viability and induced apoptosis in LN18 glioblastoma cells. DNAJB6(S) protected LN18 cells against MPP+-induced apoptosis not only by suppressing Bax cleavage but also by inhibiting a series of apoptotic events including loss of mitochondrial membrane potential, increase in intracellular reactive oxygen species, and activation of caspase-9. These observations suggest that the cytoprotective effects of DNAJB6(S) may be mediated, at least in part, by the mitochondrial pathway of apoptosis.


The socioendocrinology of adolescent development in male rhesus monkeys (Macaca mulatta).
Observations were made on four captive breeding groups of rhesus monkeys in order to measure hormonal, behavioral, and genital changes in adolescent males during the annual mating season. Three questions were addressed with regard to possible effects of social environment upon reproductive maturation: (1) Does male agonistic rank influence adolescent development? (2) Does affiliation between adolescent males and adult females during the mating season influence the males' reproductive development? (3) Does maternal rank exert any effect upon reproductive maturation in adolescent sons? In many (but not all) cases male rank was positively correlated with circulating testosterone and testes weights during the mating season. Affiliative behavior (allogrooming and sexual interactions) between adolescents and adult females in their social groups bore no relationship to the degree of reproductive maturation in males. Mounts involving intromission were infrequent, but sons of high-ranking mothers gained significantly more intromissions than sons of lower-ranking females. Maternal rank was also found to correlate with circulating testosterone levels, testes weights, growth of the baculum (os penis), and maintenance of body weight in adolescent sons during the mating season. By contrast, levels of beta-endorphin in the cerebrospinal fluid of adolescent males did not correlate with social rank, testosterone levels, or genital development. These findings point to possible effects of maternal rank, as well as intermale agonistic rank, in determining reproductive maturation during adolescence in the male rhesus monkey.


Possible Roles of Hypotaurine and Thiotaurine in the Vesicomyid Clam Phreagena okutanii.
AbstractVesicomyid clams, which inhabit deep-sea hydrothermal vents and hydrocarbon seeps, are nutritionally dependent on symbiotic, chemoautotrophic bacteria that produce organic matter by using hydrogen sulfide. Vesicomyid clams absorb hydrogen sulfide from the foot and transport it in their hemolymph to symbionts in the gill. However, mechanisms to cope with hydrogen sulfide toxicity are not fully understood. Previous studies on vent-specific invertebrates, including bathymodiolin mussels, suggest that hypotaurine, a precursor of taurine, mitigates hydrogen sulfide toxicity by binding it to bisulfide ion, so as to synthesize thiotaurine. In this study, we cloned cDNAs from the vesicomyid clam Phreagena okutanii for the taurine transporter that transports hypotaurine into cells and for cysteine dioxygenase and cysteine-sulfinate decarboxylase, major enzymes involved in hypotaurine synthesis. Results of reverse-transcription polymerase chain reaction indicate that mRNAs of these three genes are most abundant in the foot, followed by the gill. However, hypotaurine and thiotaurine levels, measured by reverse-phase high-performance liquid chromatography, were low in the foot and high in the gill. In addition, thiotaurine was detected in hemolymph cells. Hypotaurine synthesized in the foot may be transported to the gill after binding to bisulfide ion, possibly by hemolymph cells.


Effects of Repeated Botulinum Toxin Treatment for Sialorrhea in Patients with Parkinson's Disease.
To evaluate the efficacy and adverse effects of repeated onabotulinumtoxinA (BoNT-A) treatment in patients suffering from Parkinson's disease (PD) with sialorrhea. A retrospective analysis of 16 patients with sialorrhea treated with BoNT-A at our movement disorders outpatient clinic was conducted from February 2009 to September 2013. A patient with adult cerebral palsy and a patient with PD who received only a single application were excluded. BoNT-A was injected into the parotid glands without ultrasound guidance. Pre-treatment sialorrhea severity was quantified according to the Drooling Frequency and Severity Scale (DFSS). The efficacy was evaluated four weeks after BoNT-A injections using DFSS and according to the subjective assessment of the patients and/or caregivers. The mean age of the patients was 70.00±9.82 years and the mean follow-up duration was 18.78±10.37 months. Totally, 37 applications were performed. The mean BoNT-A total dose was 34.35±6.41 units. The mean scores of DFSS before and after injections were 7.00±1.03 and 3.21±0.89, respectively (p<0.001). Efficacy was 100%, and the mean experienced sialorrhea improvement was 71.78±12.95%. We found a significant difference between the first and last application in the mean duration of efficacy (17.28±9.21 weeks and 18.03±9.02 weeks, respectively, p=0.001). We did not observe side effects in this study group. Repeated injections of BoNT-A are safe and effective in treating sialorrhea in patients with PD. Based on our results, it seems that there is a maintenance of efficacy after a three-year period and an increase in the mean duration of efficacy with the number of injections. Further prospective clinical studies with larger number of patients and more longer duration of follow-up are needed to confirm our results.


[Clinical data analysis of cardiovascular involvement in Behcet's disease].
To analysis the clinical features of cardiovascular involvement in Behcet's disease. We reviewed 35 medical records of Behcet's disease with cardiovascular lesions in Anzhen Hospital, Capital Medical University from January 2002 to January 2014. 77.1% patients (27/35) were male. The mean (x±s) age when cardiovascular diseases occur was 37.19±10.4 years in male and 36.0±8.6 years in female respectively. The clinical spectrum of cardiovascular abnormalities included valvular regurgitation (20, 57.1%), conduction system disturbances (10, 28.6%), intracardiac thrombosis(1, 2.9%), aneurysms of the arteries (13, 37.1%), artery stenosis or occlusion (5, 14.3%), pulmonary vascular diseases(3, 8.6%), venous thrombosis(4, 11.4%). Twenty patients had more than one of these lesions. Inflammatory indicators had no significantly difference between the above subgroups (P>0.05). Treatments included corticosteroids and immunosuppressive drugs, together with symptomatic treatments, intervention therapy and operation.Two inpatient died from multiple organ dysfunction syndrome and cardiac shock respectively. Cardiovascular involvement is a remarkable systemic lesion of Behcet's disease. Multi-subject cooperation is beneficial for the diagnosis and treatment of the disease.


[Stress test and aortic stenosis].
In patients with severe asymptomatic aortic stenosis (AS), the decision to operate is difficult. In effect, the operative mortality is not negligible (about 5% in subjects age over 75 years) while spontaneous mortality from sudden death is low (about 0.4% per year). The aim of the stress test is to detect patients who are falsely asymptomatic (due to subconscious self limitation of daily physical activity) for whom aortic valvular replacement should be proposed because of the risk of sudden death. On the other hand, if the stress test is negative (normal blood pressure elevation on effort, the absence of either any symptoms, ST segment depression of more than 2 mm, or severe ventricular rhythm disorders linked to effort), surgical intervention could (and probably should) be postponed. This article presents the studies which have allowed integration of the stress test as an aid to the decision of when to operate in patients with asymptomatic severe AS with good left ventricular function into the European and North American recommendations.


The Relationship between Ultrasonographic Features of Hepatocellular Carcinoma and the Severity of Hepatocellular Carcinoma and the Expression of PTEN and Tg737.
To investigate the relationship between the ultrasonographic features of hepatocellular carcinoma (HCC) and the severity of HCC and the expression of tumor suppressor genes PTEN and Tg737, 90 patients with primary liver cancer are selected as the study subjects. The enhancement of liver tumor in arterial phase, portal venous phase, and delayed phase is observed by contrast-enhanced ultrasound (CEUS) before operation, and the echo intensity is compared with that of surrounding liver parenchyma. Immunohistochemistry is used to detect the expression of PTEN and Tg737 in hepatocellular carcinoma and paracancerous tissues. (1) In HCC, CEUS enhancement is characterized by rapid enhancement in arterial phase, enhancement in portal venous phase and delayed phase, and decreased hypoechoic changes. About 78.0% of the stage I-II liver cancer and 85.0% of the stage III-IV liver cancer show rapid enhancement and high echo in the arterial phase; only 8.0% of the stage I-II liver cancer shows moderate echo changes in the portal venous phase, while 32.5% (13/40) stage III-IV liver cancer shows moderate echo changes in the portal venous phase. (2) The positive rates of PTEN in liver cancer tissues and paracancerous tissues are 21.1% (19/90) and 70.0% (63/90), respectively, and the difference is statistically significant. The positive rates of Tg737 in liver cancer tissues and paracancerous tissues are 17.8% (16/90) and 75.6% (68/90), respectively, and the difference is statistically significant. Compared with PTEN and Tg737 negative groups, the ascending slope (RS) and initial elimination time (WT) of PTEN and Tg737 positive groups are significantly higher, indicating that the inflow velocity of contrast medium in the positive group is higher, the outflow time is shorter, and the lesions shows low enhancement rapidly. However, the expression of PTEN and Tg737 had no significant difference in maximal intensity (IMAX), peak time (TTP), and mean transit time (mTT). (3) Correlation analysis shows that the immunohistochemical scores of PTEN and Tg737 are not significantly correlated with IMAX, mTT, and TTP but positively correlated with RS (r = 0.359,P < 0.05), suggesting that the positive expressions of PTEN and Tg737 are negatively correlated with the inflow velocity of contrast medium. The immunohistochemical scores of PTEN and Tg737 are negatively correlated with WT, which indicated that the higher the expression intensity of PTEN is, the longer the outflow time of contrast medium is and the slower the outflow of contrast medium is. There is a significant correlation between the expression of PTEN and Tg737 proteins and CEUS parameters in hepatocellular carcinoma.


Involvement of multiple P2Y receptors and signaling pathways in the action of adenine nucleotides diphosphates on human monocyte-derived dendritic cells.
Adenosine 5'-triphosphate (ATP), which is released from necrotic cells, induces a semimaturation state of dendritic cells (DC), characterized by the up-regulation of costimulatory molecules and the inhibition of proinflammatory cytokines. This action is mediated by cyclic adenosine monophosphate (cAMP) and involves the P2Y11 receptor. As DC express the ecto-enzyme CD39, which converts ATP into adenosine 5'-diphosphate (ADP), the effects of adenine nucleotides diphosphates on molecular signaling [intracellular calcium ([Ca2+]i), cAMP, extracellular signal-regulated kinase 1 (ERK1)], costimulatory molecule expression (CD83), and cytokine production [interleukin (IL)-12, tumor necrosis factor alpha (TNF-alpha), IL-10] were investigated in human monocyte-derived DC. ADP, 2-methylthio-ADP, and ADPbetaS had no effect on cAMP, increased [Ca2+]i, and stimulated the phosphorylation of ERK1. The effect on ERK1 was inhibited by AR-C69931MX, a P2Y12 and P2Y13 antagonist. On the contrary the effect on [Ca2+]i was neither inhibited by AR-C69931MX or by the P2Y1 antagonist MRS-2179. Both effects were inhibited by pertussis toxin. ADPbetaS alone was less potent for up-regulation of CD83 than ATPgammaS and did not increase the CD83 expression by DC stimulated with lipopolysaccharide (LPS). Similar to ATPgammaS, ADPbetaS inhibited the release of IL-12p40, IL-12p70, and TNF-alpha stimulated by LPS (1-100 ng/ml). The inhibitory effect of ADPbetaS on IL-12 release was neither reversed by AR-C69931MX or by MRS-2179. The two nucleotides had opposite effects on IL-10 production: inhibition by ADPbetaS and potentiation by ATPgammaS. In conclusion, ATP can modulate the function of DC, directly via a cAMP increase mediated by the P2Y11 receptor and indirectly via its degradation into ADP, which acts via Gi-coupled receptors coupled to ERK activation and calcium mobilization. These distinct mechanisms converge on the inhibition of inflammatory cytokine production, particularly IL-12, but have a differential effect on IL-10.


Release of simvastatin from scaffolds of poly(lactic-co-glycolic) acid and biphasic ceramic designed for bone tissue regeneration.
The aim of this study was to evaluate the release of simvastatin from scaffolds composed of poly(lactic-co-glycolic) acid (PLGA) and biphasic ceramic designed for bone engineering and to assess the physico-chemical and mechanical properties of the scaffolds. Samples with 30% and 70% porosity were obtained with 0, 2, 5, and 8 wt %. of simvastatin through the solvent evaporation technique and leaching of sucrose particles. Scaffold degradation and simvastatin release were evaluated in phosphate-buffered saline. Scaffolds were analyzed by scanning electron microscopy and microtomography for two-dimensional and three-dimensional morphological characterization of the porosity, connectivity, and intrinsic permeability. The mechanical characterization was conducted based on the compressive strength and the chemical characterization by differential scanning calorimetry and energy dispersive X-ray spectroscopy. Gradual and prolonged simvastatin release from the scaffolds was observed. The release followed the Korsmeyer kinetics model with the predominance of case II transport for 30% porosity scaffolds, and anomalous behavior for the 70% porosity samples. Simvastatin release was also influenced by the slow scaffold degradation due to the strong chemical interaction between simvastatin and PLGA, as observed by differential scanning calorimetry. The scaffolds presented spherical and sucrose crystal-shaped pores that resulted in a homogenous porosity, with a predominance of open pores, ensuring interconnectivity. Simvastatin incorporation into the scaffolds and increased porosity did not influence the mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties, a promise for applications in bone regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2152-2164, 2019.


CRELD2, endoplasmic reticulum stress, and human diseases.
CRELD2, a member of the cysteine-rich epidermal growth factor-like domain (CRELD) protein family, is both an endoplasmic reticulum (ER)-resident protein and a secretory factor. The expression and secretion of CRELD2 are dramatically induced by ER stress. CRELD2 is ubiquitously expressed in multiple tissues at different levels, suggesting its crucial and diverse roles in different tissues. Recent studies suggest that CRELD2 is associated with cartilage/bone metabolism homeostasis and pathological conditions involving ER stress such as chronic liver diseases, cardiovascular diseases, kidney diseases, and cancer. Herein, we first summarize ER stress and then critically review recent advances in the knowledge of the characteristics and functions of CRELD2 in various human diseases. Furthermore, we highlight challenges and present future directions to elucidate the roles of CRELD2 in human health and disease.


Promoting Thermodynamically Unfavorable [3,3] Rearrangements by Chemoselective Reduction.
Herein described is a strategy for promoting thermodynamically unfavorable [3,3] Cope rearrangements. 3,3-Dicyano-1,5-dienes that are resistant to the thermal rearrangement can be promoted under reductive conditions. The reduced Cope products are versatile, bifunctional building blocks.


3D continuum phonon model for group-IV 2D materials.
A general three-dimensional continuum model of phonons in two-dimensional materials is developed. Our first-principles derivation includes full consideration of the lattice anisotropy and flexural modes perpendicular to the layers and can thus be applied to any two-dimensional material. In this paper, we use the model to not only compare the phonon spectra among the group-IV materials but also to study whether these phonons differ from those of a compound material such as molybdenum disulfide. The origin of quadratic modes is clarified. Mode coupling for both graphene and silicene is obtained, contrary to previous works. Our model allows us to predict the existence of confined optical phonon modes for the group-IV materials but not for molybdenum disulfide. A comparison of the long-wavelength modes to density-functional results is included.


Is there a relationship between different types of prior bariatric surgery and post-thyroidectomy hypocalcemia?
Hypocalcemia is a common complication after total thyroidectomy (TT). A history of bariatric surgery has been identified as a risk factor for this complication. This study aimed to assess the risk of hypocalcemia post TT in patients with a history of obesity procedures: laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), and laparoscopic gastric banding (LAGB). We compared the risk of hypocalcemia post TT (serum calcium levels <8 mg/dL) between patients with restrictive (LSG and LAGB), malabsorptive (RYGB), and patients without a history of obesity surgery. Hypoparathyroidism was considered permanent if the plasma parathyroid hormone (PTH) levels at 6 months were less than 15 pg/mL (normal range: 15-65 pg/mL) and the patient still required oral calcium (calcium carbonate) and vitamin D supplementation, in addition to the supplements that were taken routinely before thyroidectomy. From the 13,242 patients who underwent TT from 2006 to 2018, 90 patients (0.7%) had a history of bariatric surgery: 35 LAGB, 29 LSG, and 26 RYGB. The risk of hypocalcemia was higher in RYGB patients (50%, n=13) than in LAGB (17.1%, n=6) or LSG patients (20.6%, n=6) (P=0.003). Furthermore, hypocalcemia risk was similar between patients with a history of restrictive procedures (18.8%, 12/64) and patients with no history of bariatric surgery (17.2%, 2,268/13,152) (P=0.4). Permanent hypoparathyroidism was observed in one and 6 patients from the LAGB and RYGB groups, respectively; however, it was not observed in any patient from the LSG group. RYGB is a risk factor for hypocalcemia post TT, while restrictive bariatric procedures are not.


Erratum.
Kim SY, Huh KH, Roh YH, Oh YJ, Park J, Choi YS. Nefopam as an adjunct to intravenous patient-controlled analgesia after renal transplantation: a randomised trial. Acta Anaesthesiologica Scandinavica, 59(8), 1068-1075. DOI: 10.1111/aas.12519. In the article "Nefopam as an adjunct to intravenous patient-controlled analgesia after renal transplantation: a randomised trial", the published title of vertical axis B in Figure 2 which is 'Pain at rest' was incorrect. The correct title of the vertical axis B is 'Pain on coughing.' The correct figure 2 has been reproduced here for clarity. We apologize for any inconvenience caused.


The Face of Chronic Migraine Which Has Started to be Clarified.
Recently, information about migraine which is generally characterized with attacks has gradually increased. In some patients with migraine, progression may be observed such that the frequency and time of the attacks are increased and an attack lasts for days. This condition is called chronic migraine (CM). According to the last classification, chronic migraine is defined as headache which occurs 15 days a month or more frequently at least 8 of which show the characteristic properties of migraine or response to migraine-specific treatment. The diagnostic cirteria of chronic migraine, its differences from other chronic daily headaches and the question if it is a migraine form with a high frequency which transforms from episodic migraine or a completely different pathophysiological picture are still contradictory. Clarifying these issues is possible with clinical studies as well as increasing the studies directed to investigate the pathophysiological mechanisms.


Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine.
A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment methods. Here, we present such a model by tachycardia-induced cardiomyopathy, which can be produced by rapid cardiac pacing in swine. A single pacing lead is introduced transvenously into fully anaesthetized healthy swine, to the apex of the right ventricle, and fixated. Its other end is then tunneled dorsally to the paravertebral region. There, it is connected to an in-house modified heart pacemaker unit that is then implanted in a subcutaneous pocket. After 4 - 8 weeks of rapid ventricular pacing at rates of 200 - 240 beats/min, physical examination revealed signs of severe heart failure - tachypnea, spontaneous sinus tachycardia, and fatigue. Echocardiography and X-ray showed dilation of all heart chambers, effusions, and severe systolic dysfunction. These findings correspond well to decompensated dilated cardiomyopathy and are also preserved after the cessation of pacing. This model of tachycardia-induced cardiomyopathy can be used for studying the pathophysiology of progressive chronic heart failure, especially hemodynamic changes caused by new treatment modalities like mechanical circulatory supports. This methodology is easy to perform and the results are robust and reproducible.


Outbreak of OXA-232-producing carbapenem-resistant Klebsiella pneumoniae ST15 in a Chinese teaching hospital: a molecular epidemiological study.
The incidence of OXA-232-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) has been on the rise in China over the past five years, potentially leading to nosocomial epidemics. This study investigates the first outbreak of CRKP in the Second Affiliated Hospital of Jiaxing University. Between February 2021 and March 2022, 21 clinical isolates of OXA-232-producing CRKP were recovered from 16 patients in the Second Affiliated Hospital of Jiaxing University. We conducted antimicrobial susceptibility tests, whole genome sequencing, and bioinformatics to determine the drug resistance profile of these clinical isolates. Whole-genome sequencing revealed that all 21 OXA-232-producing CRKP strains belonged to the sequence type 15 (ST15) and shared similar resistance, virulence genes, and plasmid types, suggesting clonal transmission between the environment and patients. Integrated genomic and epidemiological analysis traced the outbreak to two clonal transmission clusters, cluster 1 and cluster 2, including 14 and 2 patients. It was speculated that the CRKP transmission mainly occurred in the ICU, followed by brain surgery, neurosurgery, and rehabilitation department. Phylogenetic analysis indicated that the earliest outbreak might have started at least a year before the admission of the index patient, and these strains were closely related to those previously isolated from two major adjacent cities, Shanghai and Hangzhou. Comparative genomics showed that the IncFII-type and IncHI1B-type plasmids of cluster 2 had homologous recombination at the insertion sequence sites compared with the same type of plasmids in cluster 1, resulting in the insertion of 4 new drug resistance genes, including TEM-1, APH(6)-Id, APH(3'')-Ib and sul2. Our study observed the clonal spread of ST15 OXA-232-producing between patients and the hospital environment. The integration of genomic and epidemiological data offers valuable insights and facilitate the control of nosocomial transmission.


A feasibility and safety study of computed tomography-guided percutaneous microwave ablation: a novel therapy for multiple synchronous ground-glass opacities of the lung.
Purpose: The present study retrospectively evaluated the feasibility, safety, and short-term efficacy of computed tomography (CT)-guided percutaneous microwave ablation (MWA) to treat multiple synchronous ground-glass opacities (GGOs) of the lung.Materials and Methods: From October 2016 to May 2019, 33 patients (9 males and 24 females, mean age: 59.6 ± 10.0 years) with multiple GGOs (103 GGOs with mean size 12.3 ± 6.3 mm) were enrolled in this study. Patients underwent 66 procedures of CT-guided percutaneous MWA. The feasibility, safety, local progression-free survival, and overall survival were evaluated.Results: The technical success and technique efficacy rate were 100% and no MWA procedure-related deaths were reported. The median follow-up period was 18.1 (range: 6.8-37.7) months. Major complications included pneumothorax (11/66, 16.7%), pleural effusion (2/66, 3.0%), pneumonia (3/66, 4.5%), and nerve injury (1/66, 1.5%), which were well controlled by appropriate treatment. Minor complications included pneumothorax (38/66, 57.6%), pleural effusion (43/66, 65.2%), hemoptysis (13/66, 19.7%), subcutaneous emphysema (4/66, 6.1%), and hemothorax (2/66, 3.0%). Currently, all patients are alive without local progression or tumor recurrence, despite the relatively insufficient follow-up time.Conclusion: CT-guided percutaneous MWA for the treatment of multiple synchronous lung GGOs is feasible, safe, and efficacious over short-term follow-up. It may also be employed as an alternative approach for nonsurgical candidates. A longer follow-up is warranted to evaluate the oncologic outcomes.


Testing a Model of Care for Patients on Immune Checkpoint Inhibitors Based on Electronic Patient-Reported Outcomes: Protocol for a Randomized Phase II Controlled Trial.
Management of severe symptomatic immune-related adverse events (IrAEs) related to immune checkpoint inhibitors (ICIs) can be facilitated by timely detection. As patients face a heterogeneous set of symptoms outside the clinical setting, remotely monitoring and assessing symptoms by using patient-reported outcomes (PROs) may result in shorter delays between symptom onset and clinician detection. We assess the effect of a model of care for remote patient monitoring and symptom management based on PRO data on the time to detection of symptomatic IrAEs from symptom onset. The secondary objectives are to assess its effects on the time between symptomatic IrAE detection and intervention, IrAE grade (severity), health-related quality of life, self-efficacy, and overall survival at 6 months. For this study, 198 patients with cancer receiving systemic treatment comprising ICIs exclusively will be recruited from 2 Swiss university hospitals. Patients are randomized (1:1) to a digital model of care (intervention) or usual care (control group). Patients are enrolled for 6 months, and they use an electronic app to complete weekly Functional Assessment of Cancer Therapy-General questionnaire and PROMIS (PROs Measurement Information System) Self-Efficacy to Manage Symptoms questionnaires. The intervention patient group completes a standard set of 37 items in a weekly PROs version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire, and active symptoms are reassessed daily for the first 3 months by using a modified 24-hour recall period. Patients can add items from the full PRO-CTCAE item library to their questionnaire. Nurses call patients in the event of new or worsening symptoms and manage them by using a standardized triage algorithm based on the United Kingdom Oncology Nursing Society 24-hour triage tool. This algorithm provides guidance on deciding if patients should receive in-person care, if monitoring should be increased, or if self-management education should be reinforced. The Institut Suisse de Recherche Expérimentale sur le Cancer Foundation and Kaiku Health Ltd funded this study. Active recruitment began since November 2021 and is projected to conclude in November 2023. Trial results are expected to be published in the first quarter of 2024 and will be disseminated through publications submitted at international scientific conferences. This trial is among the first trials to use PRO data to directly influence routine care of patients treated with ICIs and addresses some limitations in previous studies. This trial collects a wider spectrum of self-reported symptom data daily. There are some methodological limitations brought by changes in evolving treatment standards for patients with cancer. This trial's results could entail further academic discussions on the challenges of diagnosing and managing symptoms associated with treatment remotely by providing further insights into the burden symptoms represent to patients and highlight the complexity of care procedures involved in managing symptomatic IrAEs. ClinicalTrials.gov NCT05530187; https://www.clinicaltrials.gov/study/NCT05530187. DERR1-10.2196/48386.


Pharmacodynamics of cinacalcet over 48 hours in patients with controlled secondary hyperparathyroidism: useful data in clinical practice.
Cinacalcet induces immediate changes in serum PTH levels, but the pharmacodynamic effect throughout the daily dosing interval in controlled patients is unknown. Also, in patients with reduced PTH, it is unknown what happens in the first 24 hours after withdrawal. Our aim was to describe the effect over 48 hours of cinacalcet in hemodialysis patients with controlled secondary hyperparathyroidism. This was a phase 4, open-label, single-arm, single-dose, single-center clinical trial. The study was conducted at a public hospital (Hospital Perpetuo Socorro, Alicante, Spain). We included 10 patients on cinacalcet for 6 months or longer with intact PTH (iPTH) levels 100-400 pg/mL [8 men, mean age of 66 years (range 39-82 years)], chronically treated with 30 mg (n = 6), 60 mg (n = 3), or 90 mg (n = 1) of cinacalcet. A single dose (30-90 mg) was administered at baseline. iPTH (Duo Kit Scantibodies and Elecsys Roche), PTH 1-84, ionized calcium, phosphorus (P), and calcitonin were determined at baseline and at 1, 3, 6, 12, 24, and 48 hours. There was a significant reduction in iPTH between 1 and 6 hours, and values returned to baseline at 24 hours [maximum mean (95% confidence interval) percent change from baseline: -50%(-34; -66) at 3 hours]. A transient increase in calcitonin and a decrease in P were also observed, with no changes in calcium. At 48 hours, there was a significant increase in iPTH [+51% (26; 76)] and P. Changes in PTH were similar with the 3 determination methods. In hemodialysis patients with secondary hyperparathyroidism controlled by cinacalcet, a transient (1-6 hours) reduction in PTH and P and an increase in calcitonin are observed after each daily dose, with return to baseline at 24 hours. After calcimimetics discontinuation, PTH was significantly increased at 48 hours. The assay used to measure PTH does not influence relative changes induced by cinacalcet.


Influence of the new angiotensin converting enzyme inhibitor ramipril on several models of acute inflammation and the adjuvant arthritis in the rat.
Paw oedema in the rat by carrageenin and kaolin partially caused by Hageman factor activation was potentiated by the new angiotensin converting enzyme (ACE) inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl-L-alanyl]-(lS,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid] (ramipril, Hoe 498) due to its inhibition of kininase II which results in increased bradykinin levels. A dose of 1 microgram ramipril injected into the hind paw of Sprague-Dawley rats concomitantly with, or 1 mg/kg given orally 30 min before administration of the irritants, led to significantly increased inflammatory reactions. The same effects were observed when ramipril was administered 3 h after carrageenin. In the kallikrein-kinin-deficient Brown-Norway rat strain Mai Pfd/f, ramipril did not significantly alter the paw oedema induced as described above. In addition, pretreatment of Sprague-Dawley rats with 10 mg/kg i.v. bromelains completely prevented the potentiation of inflammation by ramipril. Paw oedema provoked by the Hageman factor non-activators serotonin, dextran, ovalbumin and anti-rat IgG was not potentiated by ramipril. The chronic adjuvant arthritis in Lewis rats was not influenced by daily oral treatment with 0.1-3 mg/kg ramipril. Thus, in the rat only those inflammatory reactions involving kinins, presumably generated by Hageman factor activators, are potentiated by ramipril and presumably by other ACE-inhibitors.


The comet assay for the evaluation of genotoxic potential of landfill leachate.
Genotoxic assessment of landfill leachate before and after biological treatment was conducted with two human cell lines (Me45 and NHDF) and Daphnia magna somatic cells. The alkali version of comet assay was used to examine genotoxicity of leachate by DNA strand breaks analysis and its repair dynamics. The leachate samples were collected from Zabrze landfill, situated in the Upper Silesian Industrial District, Poland. Statistically significant differences (Kruskal-Wallice ANOVA rank model) were observed between DNA strand breaks in cells incubated with leachate before and after treatment (P < 0.001). Nonparametric Friedman ANOVA confirmed time-reliable and concentration-reliable cells response to leachate concentration. Examinations of chemical properties showed a marked decrease in leachate parameters after treatment which correlate to reduced genotoxicity towards tested cells. Obtained results demonstrate that biological cotreatment of leachate together with municipal wastewater is an efficient method for its genotoxic potential reduction; however, treated leachate still possessed genotoxic character.


Effects of ceramic layer thickness, cement color, and abutment tooth color on color reproduction of feldspathic veneers.
To optimize the esthetics of ceramic restorations, it is important to determine accurately the effects of various parameters on the final color of the restoration. However, there is a lack of information on what determines the color of translucent feldspathic veneers formed using ceramics such as Vita Mark II. The aim of this study was to evaluate the effects of the ceramic layer thickness, cement color, and abutment tooth color on the color of the feldspathic ceramic veneer restoration. A total of 30 all-ceramic monolithic veneers (Vita Mark II) were fabricated using a CAD/CAM system. The crowns were divided into three groups of differing ceramic thickness (0.4-, 0.7-, and 1.0-mm thick). Each type of crown was seated on six different-colored abutment teeth (1M1 [reference], 1M2, 2M2, 3M2, 4M2, and 5M2) using seven different try-in paste colors. The color of the resulting restoration was evaluated using spectrophotometry with a spot-measurement device (Vita Easyshade Advance 4.0). Color data are expressed in CIE L*a*b* system coordinates, and color differences ΔE relative to the reference tooth were calculated and analyzed using one-way analysis of variance (ANOVA) with the Bonferroni post hoc test at α = 0.05. The color difference ΔE of the feldspathic all-ceramic veneer system was significantly affected by the thickness of the ceramic layer, the cement color, and the abutment tooth color (P < 0.05). The smallest values of ΔE compared with the reference color were found when try-in pastes shade -3 was used. As the thickness of the ceramic layer increased, a significant decrease in ΔE was found. As the color of the abutment tooth varied from light to dark, a significant increase was found in ΔE. The thickness of the ceramic layer, the cement color, and the abutment tooth color significantly affected the color of the resulting CAD/CAM feldspathic ceramic veneer restoration.


Interleukin-24 (IL-24) Expression and Biological Impact on HECV Endothelial Cells.
IL-24, also termed MDA-7, is a member of the IL-10 family of cytokines. IL-24 is reported to be expressed in a series of cell lines, including keratinocytes as well as breast, lung and prostate cancer cells, but was primarily found in a human melanoma cell line. IL-24 is suggested to have many biological properties displaying anti-tumour effects via induction of apoptosis, suppressing proliferation, invasion and metastasis of cancer cells. IL-24 has also been reported to inhibit the migration of cancer cells and keratinocytes, and have anti-angiogeneic properties. The biological functions of IL-24 are regulated through both autocrine and paracrine methods. However, currently there exists little knowledge regarding the effect of IL-24 on endothelial cell biology. The impact of rhIL-24 on human endothelial HECV cell growth, migration, trans-endothelial resistance and angiogenic potential was examined using cellular functional assays. Additionally, the relationship between IL-24 and a number of cell junction proteins were examined using immunofluorescence staining. IL-24 and receptor molecules was found to be expressed in HECV endothelial cells. Treatment of this cell line with rhIL-24 was found to promote cell migration rates and suppress tubule formation. Treatment of HECV cells with rhIL-24 can promote migration and inhibit tubule formation but does not impact cell growth or permeability at the tested concentrations. Potential links between IL-24 and AKT or PLCγ-related pathways with regard to these effects are also presented in the present study.


Predicting family burden following childhood traumatic brain injury: a cumulative risk approach.
To examine the utility of a cumulative risk index (CRI) in predicting the family burden of injury (FBI) over time in families of children with traumatic brain injury (TBI). One hundred eight children with severe or moderate TBI and their families participated in the study. The measures used in the study include the Socioeconomic Composite Index, Life Stressors and Social Resources Inventory--Adult Form, Vineland Adaptive Behavior Scales, Child Behavior Checklist, Children's Depression Inventory, McMaster Family Assessment Device, Brief Symptom Inventory, and Family Burden of Injury Interview. In addition, information on injury-related risk was obtained via medical charts. Participants were assessed immediately, 6, and 12 months postinjury and at a 4-year extended follow-up. Risk variables were dichotomized (ie, high- or low-risk) and summed to create a CRI for each child. The CRI predicted the FBI at all assessments, even after accounting for autocorrelations across repeated assessments. Path coefficients between the outcome measures at each time point were significant, as were all path coefficients from the CRI to family burden at each time point. In addition, all fit indices were above the recommended guidelines, and the chi statistic indicated a good fit to the data. The current study provides initial support for the utility of a CRI (ie, an index of accumulated risk factors) in predicting family outcomes over time for children with TBI. The time period immediately after injury best predicts the future levels of FBI; however, cumulative risk continues to influence the change across successive postinjury assessments. These results suggest that clinical interventions could be proactive or preventive by intervening with identified "at-risk" subgroups immediately following injury.


An Artificial Liposome Compartment with Size Exclusion Molecular Transport.
The cellular compartment plays an essential role in organizing the complex and diverse biochemical reactions within the cell. By mimicking the function of such cellular compartments, the challenge of constructing artificial compartments has been taken up to develop new biochemical tools for efficient material production and diagnostics. The important features required for the artificial compartment are that it isolates the interior from the external environment and is further functionalized to control the transport of target chemicals to regulate the interior concentration of both substrate and reaction products. In this study, an artificial compartment with size-selective molecular transport function was constructed by using a DNA origami-guided liposome prepared by modifying the method reported by Perrault et al. This completely isolates the liposome interior, including the DNA origami skeleton, from the external environment and allows the assembly of a defined number of molecules of interest inside and/or outside the compartment. By incorporating a bacterial membrane protein, OmpF, into the liposome, the resulting artificial compartment was shown to transport only the molecule of interest with a molecular weight below 600 Da from the external environment into the interior of the compartment.


[Echo-guided puncture of intraprostatic cysts: our experience].
Prostatic cysts are a pathological condition which is rare and still poorly known. In the past a precise diagnosis was difficult and was made with radiologic examination and/or cystoscopy and/or surgery. Up to date echotomography is the most important technique not only for the diagnosis but also for the treatment of prostatic cysts. The Authors relate upon their experience about diagnosis and treatment of prostatic cysts.


[Barrett's esophagus: epidemiology diagnosis and treatment in 2005].
Barrett's oesophagus is a complication of gastro-oesophageal reflux disease and should be considered as a major risk factor for the development of adenocarcinoma of the oesophagus. Each and every patient with Barrett's oesophagus should be enrolled in a endoscopic surveillance program. During the last years, the endoscopic treatment of high grade dysplasia or intramucosal adenocarcinoma (by mucosectomy) has been reported to be successful in relatively large series of patients. This therapeutic option is particularly useful for patients with a high operative risk. It can be applied for lesions detected at an early stage only (i.e., usually detected in the setting of a surveillance program). Therefore, non-operability is not considered as an exclusion criteria of such programs anymore.


Group psychotherapy for persons with HIV and AIDS-related illnesses.
Although some individuals are able to cope well with the challenges posed by HIV and AIDS, others experience psychological difficulties. This article reviews factors that facilitate or hinder successful coping with HIV including preexisting psychological functioning, medical health status, quality and adequacy of social support, stress-and-coping style, and perceived expected benefits of treatment. The article reviews studies evaluating the effects of group psychotherapy intervention for persons living with HIV. The article then describes clinical issues encountered in therapy groups for persons with HIV. These clinical issues include the presence of coexisting problems unrelated to HIV/AIDS, disclosure of HIV-positive serostatus to others, making changes in transmission-risk-behavior practices, AIDS-related bereavement and caregiving stress, establishing social supports, adhering to medical care regimens, and developing a positive self-identity as a person living with HIV. Practical considerations of group therapy for HIV-positive clients are also described.