Kawasaki disease: Medical therapies.
Medical therapies in patients with Kawasaki disease (KD) are administered to reduce the prevalence of coronary aneurysms, reduce systemic inflammation, and prevent coronary thrombosis. All patients with acute KD should be treated with intravenous immunoglobulin (IVIG) 2 g/kg, generally administered over 10-12 hours. Aspirin has never been shown to prevent aneurysms, but is given for its anti-inflammatory and antipyretic effects until the patient has been afebrile for ∼2 days, then lowered to an antiplatelet dose. Adjunctive therapy with a longer course of corticosteroids, together with IVIG and aspirin, may be considered for primary treatment in patients at high risk for development of aneurysms. For patients who have persistent or recrudescent fever after IVIG treatment without other explanation, adjunctive therapies include retreatment with IVIG, a tapering course of corticosteroids, infliximab, cyclosporine, cyclophosphamide, and other immunomodulatory therapies. Antithrombotic therapies are tailored to the risk of thrombosis, and range from aspirin alone for 4-6 weeks in children without aneurysms to a combination of anticoagulation and antiplatelet therapy for those with giant aneurysms.


Anti-influenza drugs: the development of sialidase inhibitors.
Viruses, particularly those that are harmful to humans, are the 'silent terrorists' of the twenty-first century. Well over four million humans die per annum as a result of viral infections alone. The scourge of influenza virus has plagued mankind throughout the ages. The fact that new viral strains emerge on a regular basis, particularly out of Asia, establishes a continual socio-economic threat to mankind. The arrival of the highly pathogenic avian influenza H5N1 heightened the threat of a potential human pandemic to the point where many countries have put in place 'preparedness plans' to defend against such an outcome. The discovery of the first designer influenza virus sialidase inhibitor and anti-influenza drug Relenza, and subsequently Tamiflu, has now inspired a number of continuing efforts towards the discovery of next generation anti-influenza drugs. Such drugs may act as 'first-line-of-defence' against the spread of influenza infection and buy time for necessary vaccine development particularly in a human pandemic setting. Furthermore, the fact that influenza virus can develop resistance to therapeutics makes these continuing efforts extremely important. An overview of the role of the virus-associated glycoprotein sialidase (neuraminidase) and some of the most recent developments towards the discovery of anti-influenza drugs based on the inhibition of influenza virus sialidase is provided in this chapter.


The Agrobacterium tumefaciens T pilus composed of cyclic T pilin is highly resilient to extreme environments.
Agrobacterium tumefaciens T pili are long semi-rigid, flexuous filaments of 10 nm diameter that are primarily composed of T pilin cyclized protein subunits. The cyclic character of T pilin apparently confers a high level of structural stability on the T pilus. Purified T pili subjected to extreme environmental conditions such as acid and alkali, including glycerol remained relatively unaffected morphologically. T pili lost their semi-rigidity when subjected to high temperatures and high pH, and dissociated into donut shaped subunits when exposed to Triton X-100. Sodium dodecyl sulfate increased the uptake of uranyl acetate exposing a 2 nm wide lumen running the length of the T pilus filament.


PKCα and PKCδ activation regulates transcriptional activity and degradation of progesterone receptor in human astrocytoma cells.
Progesterone regulates cancer cell proliferation and invasion through its receptors (PR-A and PR-B), whose phosphorylation modifies their transcriptional activity and induce their degradation. We identified by in silico analysis a putative residue (Ser400) in PR that might be phosphorylated by protein kinase C (PKC), a family of enzymes involved in the proliferation and infiltration of astrocytomas, the most frequent and aggressive brain tumors. A grade III human astrocytoma-derived cell line was used to study the role of PKC in PR phosphorylation, transcriptional activity, and degradation. Treatment with PKC activator [tetradecanoyl phorbol acetate (TPA)] increased PR phosphorylation in Ser400 after 5 minutes, which in turn induced PR transcriptional activity and its subsequent degradation by the 26S proteasome 3-5 hours after treatment. Silencing or inhibition of PKCα and PKCδ blocked PR phosphorylation and degradation induced by TPA. Both PR isoforms were associated with PKCα and reached the maximum association after 5 minutes of TPA addition. These data correlated with immunnofluorescence assays in which nuclear colocalization of PKCα with PR increased after TPA treatment. We observed a 2-fold increase in cell proliferation after PKC activation with TPA that was reduced with the PR antagonist, RU486. The PR S400A mutant revealed that this residue is essential for PKC-mediated PR phosphorylation and degradation. Our results show a key participation of PKCα and PKCδ in PR regulation and function.


User Interaction Modeling and Profile Extraction in Interactive Systems: A Groupware Application Case Study.
A relevant goal in human-computer interaction is to produce applications that are easy to use and well-adjusted to their users' needs. To address this problem it is important to know how users interact with the system. This work constitutes a methodological contribution capable of identifying the context of use in which users perform interactions with a groupware application (synchronous or asynchronous) and provides, using machine learning techniques, generative models of how users behave. Additionally, these models are transformed into a text that describes in natural language the main characteristics of the interaction of the users with the system.


The Moderating Effect of Childhood Maltreatment on the Relations Among PTSD Symptoms, Positive Urgency, and Negative Urgency.
Childhood maltreatment increases the risk for posttraumatic stress disorder (PTSD) and comorbid substance use disorder (SUD). One pathway by which this occurs is through impaired emotion regulation. Past research has shown that negative urgency, a deficit in the regulation of negative emotions, is strongly related to PTSD in those with comorbid SUD. However, there is minimal research on the relation between positive urgency and PTSD in those with comorbid SUD. The current study investigated the association between childhood maltreatment, positive urgency, negative urgency, and PTSD symptoms among those with SUD. Results suggested that PTSD was associated with negative urgency and positive urgency overall. Childhood maltreatment did not moderate the association between negative urgency and PTSD. Childhood emotional abuse, emotional neglect, and sexual abuse moderated the relation between positive urgency and PTSD (ΔR2 = .04 to .10). The association between PTSD and positive urgency was only significant at lower levels of emotional abuse and neglect. Future research should further examine the processing of positive emotions in those with PTSD and comorbid SUD. Findings might inform clinical interventions among populations exposed to childhood maltreatment to reduce or prevent the development of psychopathology.


[Neurologic complications in cardiac surgery patients].
Cerebral infarction and hypoxic-ischemic brain damage (HIE) may impair the recovery of a patient from otherwise successful cardiac operation. Severe neurologic complications occur in approximately 2 to 5% of cardiac surgery patients. The major risk factors can be recognized. The most common cause of cerebral infarction is a calcific embolus released during manipulation of atheromatotic aorta. HIE results from cerebral circulatory deficiency and subsequent hypoxia in the cerebral tissue. The development of complications can be prevented by restricting aortic manipulation and by optimizing the perfusion technique and other treatment during the operation.


[Results of serological surveys for leptospirosis in animals and people in the environs of 2 water reservoirs in eastern Slovakia].
The authors present the results of serological surveys for leptospirosis in rodents, cattle and humans, carried out in the vicinity of two large water reservoirs in Eastern Slovakia. Of the total number of 243 rodents covered by the surveys, 8.2% yielded positive reactions with leptospiral antigens. In most cases the sera reacted with L. grippotyphosa and L. sejroe . Of 168 samples of cattle serum, 13 serum samples, i.e. 7.7.%, yielded positive reactions, also with L. sejroe and L. grippotyphosa. In the group of serum samples obtained from humans, 28 out of 876 samples studied in the surveys, i. e. 3.1%, were positive. Among humans 6 serotypes were established; of these, L. sejroe occurred most frequently among humans, and also among domestic animals and rodents, then followed L. bratislava and L. grippotyphosa. The positive results obtained in humans, cattle and rodents with the prevalence of the same serotypes indicate the existence of close contacts of humans with animals, as well as the possibility of acquiring water-borne infection in recreation zones.


Regulation exerted by miRNAs in the promoter and UTR sequences: MDR1/P-gp expression as a particular case.
One of the common forms of multidrug resistance (MDR) is caused by activation of the mdr1 (ABCB1) gene, resulting in overexpression of P-glycoprotein (P-gp) and conferring cancer cell resistance to a broad range of chemotherapeutics. Recently, P-gp-mediated MDR has been associated with aberrant expression of microRNAs (miRNAs) in several types of cancer. miRNAs are small noncoding RNAs that regulate gene expression in a posttranscriptional manner through partial or total hybridization with specific sequences in the 3'-UTR of target mRNAs. Interestingly, there are at least two reports that suggest an additional regulation by miRNAs at the mdr1 promoter level. Here, we critically analyzed some of the miRNAs that regulate P-gp expression at two different levels: posttranscriptional and transcriptional. We proposed that the latter may occur through two possible scenarios: (1) direct miRNA hybridization with an active promoter and (2) triplex structure formation (double-stranded DNA/RNA) stabilized by Argonaute 2. Also, we classified transcriptional gene silencing (1) by homology, represented by small interfering RNAs directed to viral promoters, and (2) by complementarity (Watson-Crick/Hoogsteen base pairing), mediated by miRNAs. Transcriptional regulation could represent a new avenue of knowledge applicable to the modulation of other genes mediated by these noncoding RNAs.


Photonic jet: key role of injection for etchings with a shaped optical fiber tip.
We demonstrate the key role of the laser injection into a multimode fiber to obtain a photonic jet (PJ). PJ, a high concentrated propagating beam with a full width at half-maximum smaller than the diffraction limit, is here generated with a shaped optical fiber tip using a pulsed laser source (1064 nm, 100 ns, 35 kHz). Three optical injection systems of light are compared. For similar etched marks on silicon with diameters around 1 μm, we show that the required ablation energy is minimum when the injected light beam is close to the fundamental mode diameter of the fiber. Thus, we confirm experimentally that to obtain a PJ out of an optical fiber, light injection plays a role as important as that of the tip shape and, therefore, the role of the fundamental mode in the process.


Toll-like receptor 4 as a predictor of clinical outcomes of estrogen receptor-negative breast cancer in Saudi women.
The aim of this study was to investigate the association of the common polymorphisms of Toll-like receptor 4 (TLR-4) with breast cancer development in the Saudi Arabian population. Four TLR-4 polymorphisms (rs2770150, rs10759931, rs10759932, and rs4986790) were studied using 127 breast cancer patients and 117 controls. Relative expression of TLR-4 protein in the breast tumor and the matched normal breast tissues was determined in a large cohort of 70 clinical breast samples in a tissue micro-array format by immunohistochemistry using a specific anti-TLR-4 antibody. Our results demonstrated an increase in TLR-4 expression in estrogen receptor (ER)-, postmenopausal breast cancer patients compared to normal. We also demonstrated that the G allele of single-nucleotide polymorphism rs10759931 was found to be significantly higher in frequency among patients (36.3%) compared to the control group (26.7%), suggesting that this polymorphism is strongly associated with the development of breast cancer in this ethnic population. In addition, the TLR-4 polymorphism rs2770150 was shown to be highly correlated with breast cancer in patients over 48 years of age. The TLR-4 polymorphism rs4986790 was also found to be associated with this malignancy in the ER- patient groups. Our results suggested firstly that the variation in TLR-4 gene expression may influence breast cancer development and secondly a closely linked association between TLR-4 gene polymorphism and ER status. Our study provides support for a better understanding of the implication of TLR-4 polymorphism in breast tumorigenesis and for its eventual use as a cancer biomarker.


Design and characterization of a cryogenic linear Paul ion trap for ion-neutral reaction studies.
Ultra-high vacuum conditions are ideal for the study of trapped ions. They offer an almost perturbation-free environment, where ions confined in traps can be studied for extended periods of time-facilitating precision measurements and allowing infrequent events to be observed. However, if one wishes to study processes involving molecular ions, it is important to consider the effect of blackbody radiation (BBR). The vast majority of molecular ions interact with BBR. At 300 K, state selection in trapped molecular ions can be rapidly lost (in a matter of seconds). To address this issue, and to maintain state selectivity in trapped molecular ions, a cryogenic ion trap chamber has been constructed and characterized. At the center of the apparatus is a linear Paul ion trap, where Coulomb crystals can be formed for ion-neutral reaction studies. Optical access is provided, for lasers and for imaging of the crystals, alongside ion optics and a flight tube for recording time-of-flight mass spectra. The ion trap region, encased within two nested temperature stages, reaches temperatures below 9 K. To avoid vibrations from the cryocooler impeding laser cooling or imaging of the ions, vibration-damping elements are explicitly included. These components successfully inhibit the coupling of vibrations from the cold head to the ion trap-confirmed by accelerometer measurements and by the resolution of images recorded at the trap center (at 9 and 295 K). These results confirm that the cryogenic ion trap apparatus meets all requirements for studying ion-neutral reactions under cold, controlled conditions.


Report of the Canadian Hypertension Society Consensus Conference: 2. Diagnosis of hypertension in adults.
To update recommendations for the diagnosis of mild hypertension in adults and to assess the role of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring. Literature reviews of previous consensus conferences were updated with searches of MEDLINE for the period Jan. 1, 1988, to Nov. 15, 1991, and supplemented by reference lists and personal files. Panel members selected relevant articles and rated them according to methodologic criteria. The data extracted concerned the measurement of blood pressure, the diagnosis of hypertension, the treatment of mild hypertension, and the reliability and validity of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring in the diagnosis of mild hypertension. The recommendations made were graded according to the level of evidence available, circulated to many experts and approved at a consensus conference. Previous recommendations for the accurate measurement of blood pressure remain mostly unchanged. Antihypertensive treatment should be prescribed for patients (including the elderly) with an average diastolic blood pressure of at least 100 mm Hg, for those with isolated systolic hypertension (systolic blood pressure of at least 160 mm Hg and diastolic blood pressure of less than 90 mm Hg) and for patients with a diastolic blood pressure of 90 to 99 mm Hg and target-organ damage. Clinical judgement is required in treating patients with a diastolic blood pressure of 90 to 99 mm Hg without target-organ damage, and individual risk for cardiovascular disease must be taken into account. There is insufficient evidence to warrant the routine use of echocardiography, self-measurement of blood pressure or ambulatory blood pressure monitoring in diagnosis. Recent high-quality evidence supports several new recommendations for the diagnosis of mild hypertension in adults. Additional research is needed to determine the role of echocardiography, self-measurement of blood pressure and ambulatory blood pressure monitoring.


Identification of the binding sites of regulatory proteins in bacterial genomes.
We present an algorithm that extracts the binding sites (represented by position-specific weight matrices) for many different transcription factors from the regulatory regions of a genome, without the need for delineating groups of coregulated genes. The algorithm uses the fact that many DNA-binding proteins in bacteria bind to a bipartite motif with two short segments more conserved than the intervening region. It identifies all statistically significant patterns of the form W(1)N(x)W(2), where W(1) and W(2) are two short oligonucleotides separated by x arbitrary bases, and groups them into clusters of similar patterns. These clusters are then used to derive quantitative recognition profiles of putative regulatory proteins. For a given cluster, the algorithm finds the matching sequences plus the flanking regions in the genome and performs a multiple sequence alignment to derive position-specific weight matrices. We have analyzed the Escherichia coli genome with this algorithm and found approximately 1,500 significant patterns, which give rise to approximately 160 distinct position-specific weight matrices. A fraction of these matrices match the binding sites of one-third of the approximately 60 characterized transcription factors with high statistical significance. Many of the remaining matrices are likely to describe binding sites and regulons of uncharacterized transcription factors. The significance of these matrices was evaluated by their specificity, the location of the predicted sites, and the biological functions of the corresponding regulons, allowing us to suggest putative regulatory functions. The algorithm is efficient for analyzing newly sequenced bacterial genomes for which little is known about transcriptional regulation.


Recent insights into mechanisms of hypoxia-induced vasodilatation in the human brain.
The cerebral vasculature manages oxygen delivery by adjusting arterial blood in-flow in the face of reductions in oxygen availability. Hypoxic cerebral vasodilatation, and the associated hypoxic cerebral blood flow reactivity, involve many vascular, erythrocytic and cerebral tissue mechanisms that mediate elevations in cerebral blood flow via micro- and macrovascular dilatation. This contemporary review focuses on in vivo human work - with reference to seminal preclinical work where necessary - on hypoxic cerebrovascular reactivity, particularly where recent advancements have been made. We provide updates with the following information: in humans, hypoxic cerebral vasodilatation is partially mediated via a - likely non-obligatory - combination of: (1) nitric oxide synthases, (2) deoxygenation-coupled S-nitrosothiols, (3) potassium channel-related vascular smooth muscle hyperpolarization, and (4) prostaglandin mechanisms with some contribution from an interrelationship with reactive oxygen species. And finally, we discuss the fact that, due to the engagement of deoxyhaemoglobin-related mechanisms, reductions in O2 content via haemoglobin per se seem to account for ∼50% of that seen with hypoxic cerebral vasodilatation during hypoxaemia. We further highlight the issue that methodological impediments challenge the complete elucidation of hypoxic cerebral reactivity mechanisms in vivo in healthy humans. Future research is needed to confirm recent advancements and to reconcile human and animal findings. Further investigations are also required to extend these findings to address questions of sex-, heredity-, age-, and disease-related differences. The final step is to then ultimately translate understanding of these mechanisms into actionable, targetable pathways for the prevention and treatment of cerebral vascular dysfunction and cerebral hypoxic brain injury.


Predicting the Most Deleterious Missense Nonsynonymous Single-Nucleotide Polymorphisms of Hennekam Syndrome-Causing CCBE1 Gene, In Silico Analysis.
Hennekam lymphangiectasia-lymphedema syndrome has been linked to single-nucleotide polymorphisms in the CCBE1 (collagen and calcium-binding EGF domains 1) gene. Several bioinformatics methods were used to find the most dangerous nsSNPs that could affect CCBE1 structure and function. Using state-of-the-art in silico tools, this study examined the most pathogenic nonsynonymous single-nucleotide polymorphisms (nsSNPs) that disrupt the CCBE1 protein and extracellular matrix remodeling and migration. Our results indicate that seven nsSNPs, rs115982879, rs149792489, rs374941368, rs121908254, rs149531418, rs121908251, and rs372499913, are deleterious in the CCBE1 gene, four (G330E, C102S, C174R, and G107D) of which are the highly deleterious, two of them (G330E and G107D) have never been seen reported in the context of Hennekam syndrome. Twelve missense SNPs, rs199902030, rs267605221, rs37517418, rs80008675, rs116596858, rs116675104, rs121908252, rs147974432, rs147681552, rs192224843, rs139059968, and rs148498685, are found to revert into stop codons. Structural homology-based methods and sequence homology-based tools revealed that 8.8% of the nsSNPs are pathogenic. SIFT, PolyPhen2, M-CAP, CADD, FATHMM-MKL, DANN, PANTHER, Mutation Taster, LRT, and SNAP2 had a significant score for identifying deleterious nsSNPs. The importance of rs374941368 and rs200149541 in the prediction of post-translation changes was highlighted because it impacts a possible phosphorylation site. Gene-gene interactions revealed CCBE1's association with other genes, showing its role in a number of pathways and coexpressions. The top 16 deleterious nsSNPs found in this research should be investigated further in the future while researching diseases caused CCBE1 gene specifically HS. The FT web server predicted amino acid residues involved in the ligand-binding site of the CCBE1 protein, and two of the substitutions (R167W and T153N) were found to be involved. These highly deleterious nsSNPs can be used as marker pathogenic variants in the mutational diagnosis of the HS syndrome, and this research also offers potential insights that will aid in the development of precision medicines. CCBE1 proteins from Hennekam syndrome patients should be tested in animal models for this purpose.


[Evaluating endoscopy].
Endoscopy is a safe technique with a sensitivity and specificity superior to those of conventional diagnostic procedures, which it has consequently replaced. In doing so, it has also altered many diagnostic and therapeutic concepts. Moreover, endoscopy has positively influenced the previously unaffected course of certain diseases, e.g. upper G. I. bleeding. Endoscopy benefits both the patient and the physician. Although no complete cost-benefit analysis is available, preliminary reports have been favourable. These aspects indicate that endoscopy is highly valuable in a clinical setting. It must be pointed out, however, that endoscopy as a whole has not yet been fully analyzed in any single given clinical study.


The gut microbiota of insecticide-resistant insects houses insecticide-degrading bacteria: A potential source for biotechnological exploitation.
The exploration of new niches for microorganisms capable of degrading recalcitrant molecules is still required. We hypothesized the gut microbiota associated with insect-resistant lines carry pesticide degrading bacteria, and predicted they carry bacteria selected to degrade pesticides they were resistant to. We isolated and accessed the pesticide-degrading capacity of gut bacteria from the gut of fifth instars of Spodoptera frugiperda strains resistant to lambda-cyhalothrin, deltamethrin, chlorpyrifos ethyl, spinosad and lufenuron, using insecticide-selective media. Sixteen isolates belonging to 10 phylotypes were obtained, from which four were also associated with the susceptible strain. However, growth of gut bacteria associated with larvae from the susceptible strain was not obtained in any of the insecticide-based selective media tested. Growth of isolates was affected by the concentration of insecticides in the media, and all grew well up to 40 μg/ml. The insecticide-degrading capacity of selected isolates was assessed by GC or LC-MS/MS analyses. In conclusion, resistant strains of S. frugiperda are an excellent reservoir of insecticide-degrading bacteria with bioremediation potential. Moreover, gut-associated bacteria are subjected to the selection pressure imposed by insecticides on their hosts and may influence the metabolization of pesticides in insects.


Laser-fluoride effect on root demineralization.
Although the individual cariostatic effects of laser and fluoride have been shown, the combined effect of CO(2) laser and fluoride on root demineralization remains uncertain and was the main aim of this study. By using a pH-cycling system and Polarized Light Microscopy, we demonstrated the synergistic effect of fluoride combined with CO(2) laser treatment on reducing root demineralization. The mean lesion depths (in microm) for each group were 160 +/- 14 (Control), 113 +/- 8 (Laser treatment alone), 111 +/- 6 (Fluoride treatment alone), and 25 +/- 7 (Fluoride followed by laser treatment). A significant laser-enhanced fluoride uptake, characterized by the ToF-SIMS analysis, was revealed by the 37% and 400% increments in loosely and firmly bound fluorides (both p < 0.002) in laser-irradiated areas, compared with the non-irradiated controls. In conclusion, there is a significant synergistic effect of combined CO(2) laser and fluoride treatment on the inhibition of root demineralization, possibly due to laser-enhanced fluoride uptake in the root.


Emphysematous cystitis and bladder trigone diverticulum in a dog.
A 14-month-old, male German shepherd dog was evaluated for chronic, recurrent Escherichia coli urinary tract infection. An initial diagnosis of emphysematous cystitis was made, which resolved with appropriate antibacterial therapy. The urinary tract infection, however, did not resolve and on further investigation a bladder trigone diverticulum was evident, thought to be congenital in origin. This report describes the apparent ultrasonographic and radiological changes, and surgical repair of the diverticulum, and reviews the literature with regard to both congenital bladder trigone diverticulum and emphysematous cystitis. The former has never been documented in the dog and the latter is an unusual finding in a non-diabetic dog.


Exchange Phenomena in the Electron Paramagnetic Resonance Spectra of the Nitroxyl and Trityl Radicals: Multifunctional Spectroscopy and Imaging of Local Chemical Microenvironment.
This Feature overviews the basic principles of using stable organic radicals involved in reversible exchange processes as functional paramagnetic probes. We demonstrate that these probes in combination with electron paramagnetic resonance (EPR)-based spectroscopy and imaging techniques provide analytical tools for quantitative mapping of critical parameters of local chemical microenvironment. The Feature is written to be understandable to people who are laymen to the EPR field in anticipation of future progress and broad application of these tools in biological systems, especially in vivo, over the next years.


Exploration of African-American women's infant feeding choices.
It is well documented in the literature that breastfeeding is more beneficial for infants and mothers than is formula feeding. Yet, African-American women are least likely to initiate and continue breastfeeding compared to other ethnic groups. Few studies have examined African-American women's infant feeding choices from the women's perspectives. Therefore, the purpose of this exploratory study was to examine African-American women's infant feeding choices with individual narrative interviews at 3 weeks postpartum. Five African-American women participated. After coding and analyzing the narrative interviews, three major themes with sub-themes emerged that identified influencing factors on participants' choices and their opinions about other women who chose formula. The women willingly shared their rationales for their infant feeding methods. In an effort to develop and implement culturally appropriate interventions and to increase breastfeeding rates in this population, further exploration of infant feeding choices from the women's perspectives is needed.


Genetic suppression of defective profilin by attenuated Myosin II reveals a potential role for Myosin II in actin dynamics in vivo in fission yeast.
The actin cytoskeleton plays a variety of roles in eukaryotic cell physiology, ranging from cell polarity and migration to cytokinesis. Key to the function of the actin cytoskeleton is the mechanisms that control its assembly, stability, and turnover. Through genetic analyses in Schizosaccharomyces pombe, we found that myo2-S1 (myo2-G515D), a Myosin II mutant allele, was capable of rescuing lethality caused by partial defects in actin nucleation/stability caused, for example, through compromised function of the actin-binding protein Cdc3-profilin. The mutation in myo2-S1 affects the activation loop of Myosin II, which is involved in physical interaction with subdomain 1 of actin and in stimulating the ATPase activity of Myosin. Consistently, actomyosin rings in myo2-S1 cell ghosts were unstable and severely compromised in contraction on ATP addition. These studies strongly suggest a role for Myo2 in actin cytoskeletal disassembly and turnover in vivo, and that compromise of this activity leads to genetic suppression of mutants defective in actin filament assembly/stability at the division site.


INCORPORATION OF A EUROPEAN WEED INTO THE DIET OF A NORTH AMERICAN HERBIVORE.
Populations of the butterfly Euphydryas editha living within a 30 times 100-km region on the eastern slope of the Sierra Nevada range were compared for oviposition preference and ability of larvae to grow and survive on two host plants, Collinsia parviflora and Plantago lanceolata. Since its introduction approximately 100 years ago, P. lanceolata has been incorporated in the diet of E. editha in one of the study populations. The populations differed in oviposition preference; only the population that uses P. lanceolata contains some individuals that prefer P. lanceolata. Larvae from two populations, one using both P. lanceolata and C. parviflora, the other using only C. parviflora, were not found to differ in relative abilities to grow or survive on P. lanceolata. The potential for E. editha to use P. lanceolata appears in populations that have had no prior exposure to this plant, while oviposition preference for this plant has evolved in the population in which the plant now grows.


Development of the thalamo-dorsal ventricular ridge tract in the Chinese soft-shelled turtle, Pelodiscus sinensis.
With the exception of that from the olfactory system, the vertebrate sensory information is relayed by the dorsal thalamus (dTh) to be carried to the telencephalon via the thalamo-telencephalic tract. Although the trajectory of the tract from the dTh to the basal telencephalon seems to be highly conserved among amniotes, the axonal terminals vary in each group. In mammals, thalamic axons project onto the neocortex, whereas they project onto the dorsal pallium and the dorsal ventricular ridge (DVR) in reptiles and birds. To ascertain the evolutionary development of the thalamo-telencephalic connection in amniotes, we focused on reptiles. Using the Chinese soft-shelled turtle (Pelodiscus sinensis), we studied the developmental course of the thalamic axons projecting onto the DVR. We found, during the developmental period when the thalamo-DVR connection forms, that transcripts of axon guidance molecules, including EphA4 and Slit2, were expressed in the diencephalon, similar to the mouse embryo. These results suggest that the basic mechanisms responsible for the formation of the thalamo-telencephalic tract are shared across amniote lineages. Conversely, there was a characteristic difference in the expression patterns of Slit2, Netrin1, and EphrinA5 in the telencephalon between synapsid (mammalian) and diapsid (reptilian and avian) lineages. This indicates that changes in the expression domains of axon guidance molecules may modify the thalamic axon projection and lead to the diversity of neuronal circuits in amniotes.


Ultrafast demagnetization dynamics at the M edges of magnetic elements observed using a tabletop high-harmonic soft x-ray source.
We use few-femtosecond soft x-ray pulses from high-harmonic generation to extract element-specific demagnetization dynamics and hysteresis loops of a compound material for the first time. Using a geometry where high-harmonic beams are reflected from a magnetized Permalloy grating, large changes in the reflected intensity of up to 6% at the M absorption edges of Fe and Ni are observed when the magnetization is reversed. A short pump pulse is used to destroy the magnetic alignment, which allows us to measure the fastest, elementally specific demagnetization dynamics, with 55 fs time resolution. The use of high harmonics for probing magnetic materials promises to combine nanometer spatial resolution, elemental specificity, and femtosecond-to-attosecond time resolution, making it possible to address important fundamental questions in magnetism.


Short-term effects of behavioral treatment on movement initiation and postural control in Parkinson's disease: a controlled clinical study.
In a controlled clinical study, we investigated the effects of behavioral treatment on postural and gait initiation problems idiopathic Parkinson's disease (PD). Comparable groups of patients received therapy (experimental group, n = 15) and nonspecific psychological treatment (control group, n = 14) for 10 weeks. We monitored various variables reflecting properties of posture and gait initiation by using an optoelectronic motion analyzer (electronic movement analysis system, ELITE). A clinician blind to group membership of the patients assessed PD severity with the United Parkinson's Disease Rating Scale (UPDRS) before and after the treatment period. ELITE measures of postural stability and movement initiation revealed treatment-specific effects. In addition, UPDRS motor scores showed significant improvement only after behavioral treatment. We conclude that behavioral treatment in Parkinson's disease may improve motor disabilities in moderately advanced PD patients.


Antidepressant Drugs Effects on Blood Pressure.
Individuals suffering from depressive disorders display a greater incidence of hypertension compared with the general population, despite reports of the association between depression and hypotension. This phenomenon may depend, at least in part, on the use of antidepressant drugs, which may influence blood pressure through different effects on adrenergic and serotoninergic pathways, as well as on histaminergic, dopaminergic, and cholinergic systems. This review summarizes extant literature on the effect of antidepressant drugs on blood pressure. Selective serotonin reuptake inhibitors are characterized by limited effects on autonomic system activity and a lower impact on blood pressure. Thus, they represent the safest class-particularly among elderly and cardiovascular patients. Serotonin-norepinephrine reuptake inhibitors, particularly venlafaxine, carry a greater risk of hypertension, possibly related to greater effects on the sympathetic nervous system. The norepinephrine reuptake inhibitor reboxetine is considered a safe option because of its neutral effects on blood pressure in long-term studies, even if both hypotensive and hypertensive effects are reported. The dopamine-norepinephrine reuptake inhibitor bupropion can lead to blood pressure increases, usually at high doses, but may also cause orthostatic hypotension, especially in patients with cardiovascular diseases. The norepinephrine-serotonin modulators, mirtazapine and mianserin, have minimal effects on blood pressure but may rarely lead to orthostatic hypotension and falls. These adverse effects are also observed with the serotonin-reuptake modulators, nefazodone and trazodone, but seldomly with vortioxetine and vilazodone. Agomelatine, the only melatonergic antidepressant drug, may also have limited effects on blood pressure. Tricyclic antidepressants have been associated with increases in blood pressure, as well as orthostatic hypotension, particularly imipramine. Oral monoamine-oxidase inhibitors, less frequently skin patch formulations, have been associated with orthostatic hypotension or, conversely, with hypertensive crisis due to ingestion of tyramine-containing food (i.e., cheese reaction). Lastly, a hypertensive crisis may complicate antidepressant treatment as a part of the serotonin syndrome, also including neuromuscular, cognitive, and autonomic dysfunctions. Clinicians treating depressive patients should carefully consider their blood pressure status and cardiovascular comorbidities because of the effects of antidepressant drugs on blood pressure profiles and potential interactions with antihypertensive treatments.


Over-expression of fibroblast growth factor receptor 3 in human hepatocellular carcinoma.
To describe the significant over-expression of fibroblast growth factor receptor 3 (FGFR3), which is a signal transduction and cell proliferation related gene in hepatocellular carcinoma (HCC). Following DNA microarray, Northern blot and quantitative real-time PCR were employed to confirm FGFR3 expression difference in HCC tissues and surrounding non-neoplastic liver tissue. FGFR3 expression levels were further determined by immunohistochemical study in 43 cases of HCC. Northern blot results showed the significant over-expression of FGFR3 in HCC tissues, which was consistent with that from DNA microarray. Quantitative real-time PCR demonstrated that the mean ratio of FGFR3 mRNA to glyceraldehyde-3-phosphate dehydrogenase (GADPH) mRNA in HCC tissue was 0.250, whereas the ratio in non-neoplastic liver tissue was 0.014. Statistical analyses of 43 cases of HCC revealed that HCC scored higher than the matched non-neoplastic liver tissues. Examination of clinicopathological features revealed a strong correlation of over-expression of FGFR3 with poor tumor differentiation and high nuclear grade. Over-expression of FGFR3 may play an important role in liver carcinogenesis. FGFR3 may be an ideal candidate as a molecular marker in the diagnosis of HCC and a potential therapeutic target.


Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum.
Members of the Corynebacterineae, including Corynebacterium and Mycobacterium, have an atypical cell envelope characterized by an additional mycomembrane outside of the peptidoglycan layer. How this multilayered cell envelope is assembled remains unclear. Here, we tracked the assembly dynamics of different envelope layers in Corynebacterium glutamicum and Mycobacterium smegmatis by using metabolic labeling and found that the septal cell envelope is assembled sequentially in both species. Additionally, we demonstrate that in C. glutamicum, the peripheral peptidoglycan layer at the septal junction remains contiguous throughout septation, forming a diffusion barrier for the fluid mycomembrane. This diffusion barrier is resolved through perforations in the peripheral peptidoglycan, thus leading to the confluency of the mycomembrane before daughter cell separation (V snapping). Furthermore, the same junctional peptidoglycan also serves as a mechanical link holding the daughter cells together and undergoes mechanical fracture during V snapping. Finally, we show that normal V snapping in C. glutamicum depends on complete assembly of the septal cell envelope.


Succinic semialdehyde reductase Gox1801 from Gluconobacter oxydans in comparison to other succinic semialdehyde-reducing enzymes.
Gluconobacter oxydans is an industrially important bacterium that possesses many uncharacterized oxidoreductases, which might be exploited for novel biotechnological applications. In this study, gene gox1801 was homologously overexpressed in G. oxydans and it was found that the relative expression of gox1801 was 13-fold higher than that in the control strain. Gox1801 was predicted to belong to the 3-hydroxyisobutyrate dehydrogenase-type proteins. The purified enzyme had a native molecular mass of 134 kDa and forms a homotetramer. Analysis of the enzymatic activity revealed that Gox1801 is a succinic semialdehyde reductase that used NADH and NADPH as electron donors. Lower activities were observed with glyoxal, methylglyoxal, and phenylglyoxal. The enzyme was compared to the succinic semialdehyde reductase GsSSAR from Geobacter sulfurreducens and the γ-hydroxybutyrate dehydrogenase YihU from Escherichia coli K-12. The comparison revealed that Gox1801 is the first enzyme from an aerobic bacterium reducing succinic semialdehyde with high catalytic efficiency. As a novel succinic semialdehyde reductase, Gox1801 has the potential to be used in the biotechnological production of γ-hydroxybutyrate.


Pancake Bond Orders of a Series of π-Stacked Triangulene Radicals.
Conjugated radicals are capable of forming π-stacking "pancake-bonded" dimers. Members of the family of triangulene hydrocarbons, non-Kekulé neutral multiradicals, can utilize more than one singly occupied molecular orbital (SOMO) to form multiple pancake-bonded dimers with formal bond orders of up to five. The resulting dimer binding energies can be quite high and the intermolecular contacts rather small compared to the respective van der Waals values. The preferred configurations are driven by the large stabilization energy of overlapping SOMOs.


Bacillary angiomatosis associated with myositis in a patient infected with human immunodeficiency virus.
A man with AIDS presented with a deep soft-tissue mass involving the right thigh. Biopsy of a skin lesion on the back and culture of a specimen from this lesion showed bacillary angiomatosis due to Bartonella (formerly Rochalimaea) quintana. Magnetic resonance imaging revealed a large heterogeneous mass involving the vastus medialis and intermedius muscles. Therapy with erythromycin caused rapid resolution of both the cutaneous lesion and the muscle lesion. Bartonella infection is proposed as an additional cause of bacterial myositis and expands the spectrum of presentation of bacillary angiomatosis.


Cortex Cercis chinensis Granules Attenuate Streptococcus pneumoniae Virulence by Targeting Pneumolysin.
Pore-forming toxins produced by bacteria are some of the most important molecular weapons for bacterial virulence. Pneumolysin (PLY) is a pore-forming toxin secreted by Streptococcus pneumoniae (S. pneumoniae) and plays a vital role in the spread, colonization, and invasion of this bacterium in the host, indicating that PLY is a promising target for developing treatments against S. pneumoniae infection. In this study, Cortex Cercis chinensis granules (CCCGs), a prescription drug on the market, were shown to inhibit the pore-forming activity of PLY and protect against PLY-mediated cell hemolysis and A549 cell death without antibacterial activity or inhibition of PLY production. In addition, CCCG treatment inhibited the oligomerization of PLY. Animal experiments showed that CCCGs can reduce the death of mice infected with S. pneumoniae, the degree of pathological damage to the lungs, and the levels of TNF-α and IL-6 in the lungs. In summary, our results demonstrated that CCCGs, a marketed Chinese medicine, inhibit PLY activity and subsequently attenuate S. pneumoniae virulence, which would offer a novel strategy for fighting S. pneumoniae infection and a new use for CCCGs.


Analysis of LH receptor in canine ovarian follicles throughout the estrous cycle.
The aim of this study was to determine the mRNA LHR and LHR protein expression pattern in the canine ovarian follicles at different stage of development throughout the estrous cycle. Dog ovaries were obtained from 1-6y bitches at proestrus/estrus, anestrus and diestrus stages following ovariohysterectomy. Follicular cells were mechanically recovered from follicles distributed into four types (preantral, small antral, medium antral and large antral). Total RNA extraction was performed and the evaluation of gene expression levels was achieved by relative quantification q-PCR analysis. Intrafollicular amounts of LHR were assessed by western blot method. All results were evaluated by ANOVA. The expression levels of mRNA LHR in follicular cells were observed in every stage of development, however this gene expression varied over the estrous cycle. LHR transcripts increased (P < 0.05) from preantral to antral stage. There were not differences in LHR gene expression among follicles at preantral stages; however, at antral stages the lowest (P < 0.05) LHR mRNA expression was found at anestrus and the highest (P < 0.05) at proestrus/estrus. The LHR protein was also detected in dog follicles in all reproductive phases with patterns varying with stage of follicular development over the reproductive cycle. The antibody against human LHR revealed two bands at ∼90 and ∼67 kDa, probably representing the matured protein and its precursor respectively. Both bands LHR appeared already at preantral follicles increasing (P < 0.05) with growth. A high proportion of LHR was presented as immature forms in all follicles stages during different phases of the estrous cycle. In conclusion, the gene and protein of LHR are differentially expressed in dog follicles over the estrous cycle, increasing with growth and the precursor protein is the most predominant LHR form present in canine follicles.


Influence of surface sealant on the color-stability of a composite resin immersed in different beverages.
This study evaluated the influence of surface sealant (Fortify-Bisco) on the color-stability of a composite resin (Charisma-3M) immersed in different beverages. It was prepared resin specimens with 10 mm-diameter X 2 mm-thickness for each beverage (soft drink, coffee, tea and artificial saliva=control). Specimens were divided in 2 groups (with or without surface sealant) and afterwards divided in 4 subgroups (n=7) according to the immersion solution. After 24 hours, it was started the cycling in the solutions 3 times/day during 5 minutes for 90 days. Opacity (ΔL) and color change (ΔE) of specimens were analyzed with a spectrophotometer (BYK-Gardner) in the different groups in relation to the control group. This handheld portable equipment is unique. Composite resin showed statistically significant difference (p<0.05) in the solutions, and coffee promoted the higher color change, followed by tea and soft drink. There was no difference between specimens sealed or not. Therefore, surface sealant was inefficient on the protection against color change and coffee promoted the higher darkening of the specimens.


Tuberculosis and other clinical presentation of HIV/AIDS in patients with or without undergoing antiretroviral therapy in Kathmandu.
To screen tuberculosis (TB) and examine the clinical presentation of AIDS in HIV sero-positive persons. A Cross-sectional study was designed. One hundred HIV infected persons were randomly selected from different parts of the country visiting Tribhuvan University, Teaching Hospital, Kathmandu and different HIV/AIDS care centres. After taking informed consent, questionnaires were filled and three sputum specimens from each person were collected to investigate tuberculosis by Ziehl-Neelsen staining and culture. Data generated were entered into SPSS 11.5 and relevant statistical tools were applied. Among 100 HIV infected cases, 66 (66%) were males and 34 (34%) were females. Sixty percent of the cases were in the age group of 21-30 years. Majority of them were Smokers (41%), alcoholics (34%), illiterates (54%) and unemployed (59%). Heterosexual activity (51%) was found to be the major risk factor for HIV infection. Of the 100 HIV cases, 23 (23%) were co-infected with tuberculosis of which 18(78%) were sputum smear negative tuberculosis, mostly developed in late stage of HIV infection. Weight loss (54%) and diarrhoea (43%) were the major clinical presentations of AIDS. Antiretro-viral therapy non-receiver were more likely to suffer with various clinical disorders/TB as compared to ARV therapy receiver but the values were statistically insignificant, 2 values ranging from 0.003 to 2.24, p>0.05. Prevalence of tuberculosis was still high in HIV/AIDS patients, and specifically, sputum smear negative tuberculosis cases constituted the significant proportion, particularly in late stage of HIV infection. Weight loss and diarrhoea were found to be the major clinical presentation of AIDS. Illiterate and unemployed young adults involved in unsafe sexual practice and drug addiction were high risk of acquiring HIV infection. Key words: Clinical features, HIV/AIDS, Kathmandu; Smear Negative Tuberculosis.


[A Case of Systemic Polyarteritis Nodosa Presenting with Scrotal Pain].
A 76-year-old man with a history of hypertension was admitted with high fever and left scrotal pain. Laboratory findings revealed high serum C-reactive protein levels. The left epididymis appeared to be swollen on computed tomography. The patient was diagnosed with bacterial epididymitis and treatment with antibiotics was initiated. Despite treatment, his left scrotal pain and fever did not improve. Additionally, he developed right scrotal and posterior neck pain. For histopathological diagnosis, a left high orchiectomy was performed and the findings revealed thickened arteriolar walls with infiltration of inflammatory cells around the testis, leading to a final diagnosis of systemic polyarteritis nodosa. Treatment with steroids led to complete resolution of the patient's systemic pain and inflammation.


A randomized clinical trial of nebulized magnesium sulfate in addition to albuterol in the treatment of acute mild-to-moderate asthma exacerbations in adults.
We sought to compare the efficacy and safety of nebulized magnesium sulfate (MgSO(4)) plus albuterol with that of albuterol alone in adult patients with mild-to-moderate acute asthma exacerbations. Patients were randomized to receive nebulized MgSO(4) (384 mg in 6 mL of sterile water) or an equal volume of placebo (normal saline solution) in a double-blind fashion after each dose of nebulized albuterol administered (2.5 mg/3 mL) every 20 minutes for the first hour of the study. Spirometry was performed at baseline and every 20 minutes for 2 hours. Monitoring for safety included vital signs, pulse oximetry, and serum magnesium levels. Improvement in percent predicted forced expiratory volume in 1 second was chosen as a primary efficacy end point. Among 74 patients enrolled, 37 were randomized to each of 2 study groups. There were no statistically or clinically significant differences between the 2 study groups in percent predicted forced expiratory volume in 1 second at any point during the trial or overall. There were no significant differences in vital signs, pulse oximetry, or serum magnesium levels at any point during the study. The combination of nebulized MgSO(4) and albuterol provides no benefit in addition to that provided by therapy with albuterol in adult patients with mild-to-moderate asthma exacerbations. The efficacy of nebulized MgSO(4) in patients with severe asthma exacerbations remains unknown.


Dislocation Reduction and Stress Relaxation of GaN and InGaN Multiple Quantum Wells with Improved Performance via Serpentine Channel Patterned Mask.
The existence of high threading dislocation density (TDD) in GaN-based epilayers is a long unsolved problem, which hinders further applications of defect-sensitive GaN-based devices. Multiple-modulation of epitaxial lateral overgrowth (ELOG) is used to achieve high-quality GaN template on a novel serpentine channel patterned sapphire substrate (SCPSS). The dislocation blocking brought by the serpentine channel patterned mask, coupled with repeated dislocation bending, can reduce the dislocation density to a yet-to-be-optimized level of ∼2 × 10(5) to 2 × 10(6) cm(-2). About 80% area utilization rate of GaN with low TDD and stress relaxation is obtained. The periodical variations of dislocation density, optical properties and residual stress in GaN-based epilayers on SCPSS are analyzed. The quantum efficiency of InGaN/GaN multiple quantum wells (MQWs) on it can be increased by 52% compared with the conventional sapphire substrate. The reduced nonradiative recombination centers, the enhanced carrier localization, and the suppressed quantum confined Stark effect, are the main determinants of improved luminous performance in MQWs on SCPSS. This developed ELOG on serpentine shaped mask needs no interruption and regrowth, which can be a promising candidate for the heteroepitaxy of semipolar/nonpolar GaN and GaAs with high quality.


Multivariate Analysis of Factors Associated with the Koebner Phenomenon in Vitiligo: An Observational Study of 381 Patients.
The Koebner phenomenon (KP) is a common entity observed in dermatological disorders. The reported incidence of KP in vitiligo varies widely. Although the KP is frequently observed in patients with viltiligo, the associated factors with KP has not been established yet. The aim is to estimate the prevalence of KP in vitiligo patients and to investigate the associated factors with KP among vitiligo characteristics. A cross-sectional observational study was conducted using 381 vitiligo patients. Demographic and clinical information was obtained via the completion of Vitiligo European Task Force (VETF) questionnaires. Patients with positive history of KP were extracted from this vitiligo database. Multivariate analysis was performed to assess associations with KP. The median age of cases was 24 years (range, 0.6~76). In total, 237 of the patients were male (62.2%). Vitiligo vulgaris was the most common type observed (152/381, 39.9%). Seventy-two percent (274/381) patients did not exhibit KP, whereas 28.1% (107/381) of patients exhibited this condition. Multivariable analysis showed the following to be independent factors with KP in patients with vitiligo: the progressive disease (odds ratio [OR], 1.82; 95% confidence interval [95% CI], 1.17~2.92; p=0.041), disease duration longer than 5 years (OR, 1.92; 95% CI, 1.22~2.11; p=0.003), and body surface area more than 2% (OR, 2.20; 95% CI, 1.26~3.24; p<0.001). Our results suggest that KP may be used to evaluate disease activity and investigate different associations between the clinical profile and course of vitiligo. Further studies are needed to predict the relationship between KP and responsiveness to therapy.


Left Ventricular Assist Device.
Left ventricular assist device (LVADs) have been used with increasing frequency since the late 1980s. Technology has improved these devices to make them less thrombogenic and has decreased their size to allow greater application. By definition, the LVAD only assists or supports the pumping function of the left ventricle, unlike cardiopulmonary bypass which provides total circulatory and pulmonary function. LVADs support the circulation for hours to days and occasionally for weeks when the left and/or right ventricle has failed and is therefore unable to sustain the circulation. The hope is that by temporarily supporting the circulation, ventricular function will return. In other instances, LVAD type devices (also known as prosthetic ventricles) are used to 'bridge' the time until a suitable heart donor can be located for transplantation.


Spare non-occupational HIV post-exposure prophylaxis by active contacting and testing of the source person.
HIV-1 post-exposure prophylaxis (PEP) is frequently prescribed after exposure to source persons with an undetermined HIV serostatus. To reduce unnecessary use of PEP, we implemented a policy including active contacting of source persons and the availability of free, anonymous HIV testing ('PEP policy'). All consultations for potential non-occupational HIV exposures i.e. outside the medical environment) were prospectively recorded. The impact of the PEP policy on PEP prescription and costs was analysed and modelled. Among 146 putative exposures, 47 involved a source person already known to be HIV positive and 23 had no indication for PEP. The remaining 76 exposures involved a source person of unknown HIV serostatus. Of 33 (43.4%) exposures for which the source person could be contacted and tested, PEP was avoided in 24 (72.7%), initiated and discontinued in seven (21.2%), and prescribed and completed in two (6.1%). In contrast, of 43 (56.6%) exposures for which the source person could not be tested, PEP was prescribed in 35 (81.4%), P < 0.001. Upon modelling, the PEP policy allowed a 31% reduction of cost for management of exposures to source persons of unknown HIV serostatus. The policy was cost-saving for HIV prevalence of up to 70% in the source population. The availability of all the source persons for testing would have reduced cost by 64%. In the management of non-occupational HIV exposures, active contacting and free, anonymous testing of source persons proved feasible. This policy resulted in a decrease in prescription of PEP, proved to be cost-saving, and presumably helped to avoid unnecessary toxicity and psychological stress.


Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and Immunomodulation.
The vision of a precision medicine-guided approach to novel cancer drug development is challenged by high intratumor heterogeneity and interpatient diversity. This complexity is rarely modeled accurately during preclinical drug development, hampering predictions of clinical drug efficacy. To address this issue, we developed Comparative In Vivo Oncology (CIVO) arrayed microinjection technology to test tumor responsiveness to simultaneous microdoses of multiple drugs directly in a patient's tumor. Here, in a study of 18 canine patients with soft tissue sarcoma (STS), CIVO captured complex, patient-specific tumor responses encompassing both cancer cells and multiple immune infiltrates following localized exposure to different chemotherapy agents. CIVO also classified patient-specific tumor resistance to the most effective agent, doxorubicin, and further enabled assessment of a preclinical autophagy inhibitor, PS-1001, to reverse doxorubicin resistance. In a CIVO-identified subset of doxorubicin-resistant tumors, PS-1001 resulted in enhanced antitumor activity, increased infiltration of macrophages, and skewed this infiltrate toward M1 polarization. The ability to evaluate and cross-compare multiple drugs and drug combinations simultaneously in living tumors and across a diverse immunocompetent patient population may provide a foundation from which to make informed drug development decisions. This method also represents a viable functional approach to complement current precision oncology strategies. Cancer Res; 77(11); 2869-80. ©2017 AACR.


Mitochondrial respiration at low levels of oxygen and cytochrome c.
In the intracellular microenvironment of active muscle tissue, high rates of respiration are maintained at near-limiting oxygen concentrations. The respiration of isolated heart mitochondria is a hyperbolic function of oxygen concentration and half-maximal rates were obtained at 0.4 and 0.7 microM O(2) with substrates for the respiratory chain (succinate) and cytochrome c oxidase [N,N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD)+ascorbate] respectively at 30 degrees C and with maximum ADP stimulation (State 3). The respiratory response of cytochrome c-depleted mitoplasts to external cytochrome c was biphasic with TMPD, but showed a monophasic hyperbolic function with succinate. Half-maximal stimulation of respiration was obtained at 0.4 microM cytochrome c, which was nearly identical to the high-affinity K(')(m) for cytochrome c of cytochrome c oxidase supplied with TMPD. The capacity of cytochrome c oxidase in the presence of TMPD was 2-fold higher than the capacity of the respiratory chain with succinate, measured at environmental normoxic levels. This apparent excess capacity, however, is significantly decreased under physiological intracellular oxygen conditions and declines steeply under hypoxic conditions. Similarly, the excess capacity of cytochrome c oxidase declines with progressive cytochrome c depletion. The flux control coefficient of cytochrome c oxidase, therefore, increases as a function of substrate limitation of oxygen and cytochrome c, which suggests a direct functional role for the apparent excess capacity of cytochrome c oxidase in hypoxia and under conditions of intracellular accumulation of cytochrome c after its release from mitochondria.


Saccharomyces cerevisiae MATa mutant cells defective in pointed projection formation in response to alpha-factor at high concentrations.
We have isolated Saccharomyces cerevisiae MATa mutant cells that do not form a pointed projection but elongate in response to alpha-factor at high concentrations. Complementation tests defined three genes, PPF1, PPF2, and PPF3 (for pointed projection formation), necessary for pointed projection formation. Allelism tests with genes known to be needed for projection formation revealed that PPF1 is identical to SPA2, while PPF2 and PPF3 are not allelic to SST2, STE2, SPA2, BEM1 or SLK1/SSP31/BCK1. The morphology of MATa ppf mutants treated with high concentrations of alpha-factor is similar to that of MATa PPF cells treated with alpha-factor at low concentrations. Quantitative mating tests showed that PPF2 and PPF3 are not essential for mating in either MATa or MAT alpha background. Monitoring of division arrest and expression of an alpha-factor-inducible gene revealed that mutations in the PPF genes do not affect the responses of MATa cells to low concentrations of alpha-factor. Unlike wild-type cells, the ppf mutants exhibited early recovery from alpha-factor-induced division arrest. Furthermore, vegetatively growing ppf3-1 cells are slightly defective in cell separation of mother and daughter cells and in selection of the correct bud sites in all cell types. These results indicate that PPF2 and PPF3 are involved in the response to alpha-factor at high concentrations and that PPF3 is also required for proper establishment of polarity in vegetative growth.


Organelle differentiation in the chick blastoderm during hypoblast formation.
The ultrastructure of the chick blastoderm was examined at three developmental stages, from an unincubated single-layered system through hypoblast advancement to full hypoblast formation.With the onset of incubation the nucleolus changes from a loose network of intermingled pars fibrosa and pars granulosa into a compact body with a definite matrix material.The endoplasmic reticulum, mitochondria, and Golgi complex increase in complexity and volume. In blastoderms with a fully developed hypoblast a special asymmetrical endoplasmic reticulum becomes abundant. These data are analysed in relation to similar structural differentiation of the nucleolus, endoplasmic reticulum, Golgi complex and mitochondria in the embryonic development of other vertebrate groups.The above changes in organelle structure are noted in both the epi- and the hypoblast, although these organelles become more abundant in the former. In the intermediate stage no differences are noted between epiblast cells underlined by hypoblast and those of the anterior single-layered region. The above changes in the epiblast must therefore be related to age and not to contact with the advancing hypoblast.Previous studies mentioned in the text seem to indicate that the inducing effect of the hypoblast on the epiblast is exerted after its complete formation and not during its advancement. Our results in the organelle differentiation during hypoblast formation are in accordance with this hypothesis.


An uncomfortable tension: Reconciling the principles of forensic psychology and cultural competency.
State of Washington v. Sisouvanh (2012) was the first case in which an appellate court asserted the need for cultural competence in competency-to-stand-trial evaluations. A court reiterated this need in State of Washington v. Ortiz-Abrego (2017). Research in forensic psychology seldom addressed cultural considerations in pretrial evaluations until this past decade, but the growing body of literature pales in comparison to the work found in clinical and counseling psychology. Most of the current literature acknowledges the lack of professionally sanctioned practice guidelines and makes valuable suggestions regarding how to address cultural factors that are relevant to the requisite capacities of legal competency. Yet, none of this research addresses potential risks incurred by the evaluators who attempt to incorporate these suggestions into practice or acknowledges the possible incompatibility between forensic and cultural competency principles. The authors posit there may be areas of incompatability, or tension, between the tenets of forensic psychology and cultural competency. To examine this potential incompatibility, we reviewed legal cases with cultural implications, addressed recent developments regarding cultural "incompetence," and conducted an overview of cultural competency in clinical and forensic psychology. Comparing general principles of forensic psychology with those of cultural responsiveness and humility, we found that questions emerged regarding the potential philosophical conflicts as well as risks that may be incurred by individual evaluators in legal settings. The resultant dilemma sets the stage for pragmatic suggestions regarding communication, assessment, and diagnosis. Finally, we emphasize the need for sanctioned practice guidelines. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


A combined ligand-based and target-based drug design approach for G-protein coupled receptors: application to salvinorin A, a selective kappa opioid receptor agonist.
Combined ligand-based and target-based drug design approaches provide a synergistic advantage over either method individually. Therefore, we set out to develop a powerful virtual screening model to identify novel molecular scaffolds as potential leads for the human KOP (hKOP) receptor employing a combined approach. Utilizing a set of recently reported derivatives of salvinorin A, a structurally unique KOP receptor agonist, a pharmacophore model was developed that consisted of two hydrogen bond acceptor and three hydrophobic features. The model was cross-validated by randomizing the data using the CatScramble technique. Further validation was carried out using a test set that performed well in classifying active and inactive molecules correctly. Simultaneously, a bovine rhodopsin based "agonist-bound" hKOP receptor model was also generated. The model provided more accurate information about the putative binding site of salvinorin A based ligands. Several protein structure-checking programs were used to validate the model. In addition, this model was in agreement with the mutation experiments carried out on KOP receptor. The predictive ability of the model was evaluated by docking a set of known KOP receptor agonists into the active site of this model. The docked scores correlated reasonably well with experimental pK (i) values. It is hypothesized that the integration of these two independently generated models would enable a swift and reliable identification of new lead compounds that could reduce time and cost of hit finding within the drug discovery and development process, particularly in the case of GPCRs.


Club Cells Are the Primary Target for Permethrin-Induced Mouse Lung Tumor Formation.
Permethrin has been shown to increase lung adenomas in female CD-1 mice, but not in male mice or Wistar rats. The proposed mode of action (MOA) for permethrin-induced female mouse lung tumor formation involves morphological changes in Club cells; increased Club cell proliferation; increased Club cell hyperplasia, and lung tumor formation. In this study, the treatment of female CD-1 mice with tumorigenic doses (2500 and 5000 ppm) of permethrin, but not with a nontumorigenic dose (20 ppm), for 14 and/or 28 days increased Club cell replicative DNA synthesis. Global gene expression analysis of female mouse lung samples demonstrated that permethrin treatment up-regulated 3 genes associated with cell proliferation, namely aldehyde dehydrogenase 3a1 (Aldh3a1), oxidative stress-induced growth inhibitor 1, and thioredoxin reductase 1. Treatment with 2500 and 5000 ppm, but not 20 ppm, permethrin for 7 days produced significant increases in mRNA levels of these 3 genes. Immunohistochemical analysis demonstrated that Club cell secretory protein, CYP2F2, and ALDH3A1 colocalized in Club cells; confirmed by flow cytometry analysis of lung cells employing KI67 as a cell proliferation marker. Overall, the present data extend the proposed MOA by demonstrating that Club cells are the primary initial target of permethrin administration in female mouse lungs. As humans are quantitatively much less sensitive to agents that increase Club cell proliferation and lung tumor formation in mice, it is most likely that permethrin could not produce lung tumors in humans. This conclusion is supported by available negative epidemiological data from several studies.


Properties of biophotons and their theoretical implications.
The word "biophotons" is used to denote a permanent spontaneous photon emission from all living systems. It displays a few up to some hundred photons/(s x cm2) within the spectral range from at least 260 to 800 nm. It is closely linked to delayed luminescence (DL) of biological tissues which describes the long term and ultra weak reemission of photons after exposure to light illumination. During relaxation DL turns continuously into the steady state biophoton emission, where both, DL and biophoton emission exhibit mode coupling over the entire spectrum and a Poissonian photo count distribution. DL is representing excited states of the biophoton field. The physical properties indicate that biophotons originate from fully coherent and sometimes even squeezed states. The physical analysis provides thermodynamic and quantum optical interpretation, in order to understand the biological impacts of biophotons. Biological phenomena like intracellular and intercellular communication, cell growth and differentiation, interactions among biological systems (like "Gestaltbildung" or swarming), and microbial infections can be understood in terms of biophotons. "Biophotonics", the corresponding field of applications, provide a new powerful tool for assessing the quality of food (like freshness and shelf life), microbial infections, environmental influences and for substantiating medical diagnosis and therapy.


Freeze tolerance, morphology, and RAPD-PCR identification of Trichinella nativa in naturally infected arctic foxes.
Arctic foxes (Alopex lagopus) were collected from Greenland and Svalbard (N = 319). Twenty-four were infected with Trichinella (7.5%). Molecular analysis (random-amplified polymorphic DNA polymerase chain reaction) confirmed that all animals were infected with Trichinella nativa. Motile larvae were found in muscle tissue from all foxes after carcasses had been frozen for 1 yr at -18 C. Infective larvae were found in 2 foxes after a total of 4 yr storage at -18 C, which is longer than any previous observations. Morphological examination of the cysts showed large nurse cells and significant deposition of collagen and connective tissue. It is suggested that, within the geographical distribution of T. nativa, the more freeze-resistant isolates are found at higher latitudes.


[Quality control of the assay of receptors in human breast tumors].
Many technical problems are encountered when measuring estradiol and progesterone receptors in breast tumors biopsies. They are due to both intrinsic characteristics of the tissue, and to receptors instability. Suggestions are made to establish an internal quality control in each laboratory at the different steps: obtention and storage of biopsies, purity checking of the reagents, control of the assay protocol, and calculations. Several methods to prepare control pools have been proposed. They use either mammary tumors or animal target organs, and stable concentrations of receptors have been obtained by storage in liquid nitrogen or lyophilization. Published studies have demonstrated important interlaboratory variations. These discrepancies might be in part reduced by using the same assay protocol in the different participating laboratories.


LIN28B in constitutional delay of growth and puberty.
Recently variation in LIN28B, a human ortholog of the gene-regulating processing of micro-RNAs (miRNAs) controlling the timing of major developmental events in the nematode Caenorhabditis elegans, was reported to be associated with timing of puberty in humans. In C. elegans, a gain-of-function allele of lin-28 causes a retarded phenotype. The objective of the study was to evaluate the variation in the LIN28B gene in 145 subjects with constitutional delay of growth and puberty (CDGP). For this study, 115 males and 30 females with CDGP were included. CDGP was defined by Tanner genital or breast stage II and pubertal growth spurt taking place 2 SD later than average. The four coding exons (exons 1-4) and exon-intron boundaries, as well as the fragment of 3' untranslated region containing miRNA recognition elements A and B, of LIN28B were PCR amplified from genomic DNA obtained from peripheral blood leukocytes of the subjects and bidirectionally sequenced. No variation in the coding region of LIN28B in the 145 subjects with CDGP was found. However, 16 of 145 subjects carried a 2-nucleotide deletion immediately 5' from miRNA recognition element A. These patients did not differ in phenotypic features as compared with noncarriers, and this variant was present in 100 controls with the same frequency. Our results show that mutations in the coding region or 3' untranslated region miRNA recognition elements A and B of LIN28B do not underlie CDGP. Lack of any variation in the coding region of the gene suggests that LIN28B in developmental timing is so crucial that any changes in the conserved protein would probably be lethal.


Pharmacotherapy of bladder cancer--practice and prospects.
In contrast to the US, the incidence and mortality rates of bladder cancer are still increasing in some European countries, despite the fact that most new cases are diagnosed as early, superficial tumours. The standard of care of superficial tumours consists of cytoscopic electroresection of the tumour followed by intravesical immunotherapy or chemotherapy. Immunotherapy with bacillus-Calmette Guerin (BCG) prevents recurrence in most treated patients and has a positive impact on survival; however, approximately 30% are BCG-refractory, progressive tumours. Pharmacogenomics will enable to distinguish those high-risk patients in clinical practice soon. New immunotherapy approaches, such as BCG combined with low-dose interferon or recombinant BCG strains, are promising approaches which need to be explored in prospective trials. The use of neoadjuvant or adjuvant chemotherapy is still controversial but the results of recent trials of neoadjuvant chemotherapy in locally-advanced bladder tumours convinced some leading centres to implement neoadjuvant chemotherapy in selected groups of patients. By far, the four-drug methotrexate-vinblastine-doxorubicin-cisplatin regimen was widely used in metastatic and locally-advanced disease. Recently, two-drug combination gemcitabine-cisplatin proved to be equally effective and less toxic. New chemotherapies tested in clinical trials include gemcitabine, taxanes and new drugs that interfere with signal transduction. Individualisation of established and investigational treatment options based on molecular tumour characteristics, such as p53 status, is probably the future of bladder cancer pharmacotherapy.


Long-acting human serum albumin-thioredoxin fusion protein suppresses bleomycin-induced pulmonary fibrosis progression.
Idiopathic pulmonary fibrosis (IPF) is thought to involve inflammatory cells and reactive oxygen species (ROS), such as superoxide anion radical (O2(·-)). There is currently no effective treatment of IPF. We previously developed a human serum albumin (HSA)-thioredoxin 1 (Trx) fusion protein (HSA-Trx) designed to overcome the unfavorable pharmacokinetic and short pharmacological properties of Trx, an antioxidative and anti-inflammatory protein. In this study, we examined the therapeutic effect of HSA-Trx on an IPF animal model of bleomycin (BLM)-induced pulmonary fibrosis. A pharmacokinetic study of HSA-Trx or Trx in BLM mice showed that the plasma retention and lung distribution of Trxc was markedly improved by fusion with HSA. A weekly intravenous administration of HSA-Trx, but not Trx, ameliorated BLM-induced fibrosis, as evidenced by a histopathological analysis and pulmonary hydroxyproline levels. HSA-Trx suppressed active-transforming growth factor (TGF)-β levels in the lung and inhibited the increase of inflammatory cells in bronchoalveolar lavage fluid, pulmonary inflammatory cytokines, and oxidative stress markers. An in vitro EPR experiment using phosphate-buffered saline-stimulated neutrophils confirmed the O2(·-) scavenging ability of HSA-Trx. Furthermore, post-treatment of HSA-Trx had a suppressive effect against BLM-induced fibrosis. These results suggest that HSA-Trx has potential as a novel therapeutic agent for IPF, because of its long-acting antioxidative and anti-inflammatory modulation effects.


Minimally-invasive treatment of hepatic hydatid disease with Perforator-Grinder-Aspirator Apparatus and follow-up of 42 patients.
The gold standard treatment for hydatid cyst (HC) is surgery. In surgical practice, open procedures still remain as the first option but in this minimally-invasive era, the frequency of laparoscopic procedures is increasing. The aim of this study is to evaluate the results of 42 patients with HC who underwent surgery with Perforator-Grinder-Aspirator-Apparatus (PGAA) and demonstrate the success and reliability of this technique. The datas of 42 patients, who underwent laparoscopic surgery with PGAA between Jan 2010 and Feb 2016 were evaluated retrospectively. All patients diagnosed with ultrasonography and underwent computed tomography to identify the surgical anatomy, accessibility of the cyst and the relation with the other cysts. All patients had 10 mg/kg/day albendazole treatment at least 10 days before surgery and preoperative antibiotic prophylaxis was made by 1 gr ampicillin/sulbactam. Thirty-two patients had single cysts, 9 patients had 2 cysts and 1 patient had 3 cysts. Of the 53 cysts ; unroofing and drainage was performed to 38 cysts, unroofing-drainage and omentopexy were performed to 7 cysts and simple drainage was performed to 8 cysts. Four complications occurred after the procedure. The average duration of hospital stay was 4.73 ± 2.6 days. There are several treatment options in hydatid cyst and the most appropriate must be selected depending on the patient. We believe that the use of PGAA can increase the use of laparoscopy in cystic hydatidosis of liver and will achieve better results.


[Association of stressful life events with acute myocardial infarction in population in the city of Nis within the period from 1998-2000].
Stressful life events present a very important category of psychosocial stress. A few studies have showed that a psychosocial stress represents a very important risk factor for acute myocardial infarction (AMI), but measures of stress may not be suitable for different countries, cultures and ethnic groups. The aim of this study was to investigate the relation of stressful life events with AMI in the period of 1998-2000 in the population of the city of Nis. A case-control study included 100 patients with the first MI (in the period 1998-2000) and 100 healthy subjects, matched with respect to sex and age (+/- 2 years) from the city of Nis. The data of stressful life events were obtained by the Scaling of life events by Paykel ES, modified by the authors consistent with the examined population and the period of investigation. The Yates chi2 test, odds ratio - OR and their 99% interval of confidence were used as statistical procedures. The results showed that stressful life events in the period of investigation were very important risk factors for AMI with a statistically significant level (p = 0.000). Huge financial problems (OR = 202.36, Ci = 24.82-4387.58), violation of law (OR = 168.00, Ci = 10.66-6658.96) and serious illness of family members (OR = 159.60, Ci = 19.05- 3514.81) were the highest risk for AMI. The patients who reported that his/her son or other member of family had been gone to the army (or mobilization) before the illness onset, had 138 times higher risk of AMI (Ci = 14.98-3222.47, chi2 = 40.95, p = 0.000), while the patients who had mobilized themselves had 84 times higher risk (Ci = 7.00-2363.06, chi2= 23.87, p = 0.000). Effect of several stressful life events lead to significantly increased risk of AMI andthat significance is larger as the number of life events is more frequent (one life event: OR = 28.41, Ci = 3.73-593.52; chi2 = 17.40, p = 0.000; ? 4: OR = 336.00, Ci = 28.31-9760.28, chi2 = 50,43, p = 0,000). These findings indicate that stressful life events are associated with AMI and that they are very important for further epidemiological investigation of the triggering mechanisms and should improve preventive strategies of this serious disorder.


Using Molecular Docking to Compare Toxicity of Reactive Chemicals to Freshwater and Marine Luminous Bacteria.
Vibrio fischeri is a marine luminous bacterium that has been widely used in toxicity bioassays, while Vibrio qinghaiensis sp.-Q67 is a newly found freshwater species which is more suitable for the tests on freshwater samples. However, there is a sensitive difference between these two species due to the media, chemical modes of action and the tested species. It remains unclear how these factors induce toxicity changes in luminous bioassays. Therefore, by using molecular docking between reactive chemicals and the target proteins of Vibrio fischeri and Vibrio qinghaiensis sp.-Q67 respectively, the sensitive difference was explored from the angle of amino acid residues that involved in the interactions. Mutation of amino acid residues was performed to investigate the role of these amino acids in the interactions and the most important amino acid residues in toxicity effect were found. The results suggested tat the most important amino acid residues in toxicity effect would affect the binding affinity between chemicals and target proteins of Vibrio fischeri and Vibrio qinghaiensis sp.-Q67, and then induce distinct toxic effect on them. As there are fewer toxicity data for freshwater Vibrio qinghaiensis sp.-Q67 than for Vibrio fischeri, this study helps to take advantage of the plentiful toxicity data of Vibrio fischeri to predict toxicities of freshwater samples.


Laparoscopic Radical Cholecystectomy for Primary or Incidental Early Gallbladder Cancer: The New Rules Governing the Treatment of Gallbladder Cancer.
To evaluate the technical feasibility and oncologic safety of laparoscopic radical cholecystectomy (LRC) for primary or incidental early gallbladder cancer (GBC) treatment. Articles reporting LRC for GBC were reviewed from the first case reported in 2010 to 2015 (129 patients). 116 patients had a preoperative diagnosis of gallbladder cancer (primary GBC). 13 patients were incidental cases (IGBC) discovered during or after a laparoscopic cholecystectomy. The majority of patients who underwent LRC were pT2 (62.7% GBC and 63.6% IGBC). Parenchyma-sparing operation with wedge resection of the gallbladder bed or resection of segments IVb-V were performed principally. Laparoscopic lymphadenectomy was carried out according to the reported depth of neoplasm invasion. Lymph node retrieved ranged from 3 to 21. Some authors performed routine sampling biopsy of the inter-aorto-caval lymph nodes (16b1 station) before the radical treatment. No postoperative mortality was documented. Discharge mean day was POD 5th. 16 patients had post operative morbidities. Bile leakage was the most frequent post-operative complication. 5 y-survival rate ranged from 68.75 to 90.7 months. Laparoscopy can not be considered as a dogmatic contraindication to GBC but a primary approach for early case (pT1b and pT2) treatment.


Diagnosis and management of common maxillofacial injuries in the emergency department. Part 1: Advanced trauma life support.
Maxillofacial injuries are often seen in the emergency department. Fractures of the facial skeleton are commonly seen after assault, road traffic accidents, falls, and sporting injuries in a ratio mandibular:zygoma:maxillary of 6:2:1. Clinicians must be familiar with their management so that appropriate treatment may be used.


[Quantitative description of the resistance of microbiological indicators by means of characteristic data (author's transl)].
The ambiguity of the quantitative description of the resistance of microbiological indicators by means of the terms common thus far, namely "resistance" (maximal period of action after which all indicators still exhibit organisms capable of reproduction) and "death time" (minimal period of action after which organisms capable of reproduction cannot be demonstrated any more in any of the indicators) is shown. Among other factors, the probability that all indicators will yield identical findings (sterility or growth of surviving organisms) at a defined time, is dependent upon the number of indicators in each case. The more indicators are tested, the lower "resistance" and the later the "death time" will be. Instead of times when all indicators present an identical reaction, times (or values related to these times in a defined way) should be taken at which indicators show the absence of organisms or the presence of surviving ones with a defined frequency. There is a defined relationship between the frequency of indicators found free from (resp. containing) surviving organisms and the number of surviving organisms per indicator (cf. Figs. 1 and 2). If the regularity of the decrease of organisms with the period of action of the destroying agent is known, 2 values are sufficient for a clear description of the resistance of a preparation of microbiological indicators. As characteristic values those values of action are proposed after which 99% and 1% of indicators will exhibit surviving organisms (t99% and t1%, respectively). The period during which the dependence of the frequency of presence of sterile indicators (po) upon the period of action of the destroying agent may be determined with sufficient precision and at justifiable experimental expenditure, is corresponding to a decrease of surviving organisms to appr. 1/30. From practical experience, it will be justified in the preponderant majority of cases to assume a logarithmic orderof death as given. Under such conditions, there will be a clear relationship between lg(-ln po) and the period of action of the destroying agent, so that test results may be easily evaluated by means of a simple graphical method or regression calculation. Graphical (FIG. 3) and mathematical determination of characteristic values from the frequency of indicators exhibitoring surviving organisms in the destruction test, after different periods of action, is explained by means of an example (Fig. 3; Tables 2 and 3) and a calculation (Table 1). To keep variation of experimental results sufficiently low, at least 30 (if possible 50) indicators per period of action should be studied for surviving organisms (cf. Fig 4). When evaluating results, different weights of the individual values and their asymmetric distribution around a maximum at t80% (Fig 5) should be taken into consideration.


Gender differences in the prevalence of DSM-IV alcohol use disorders in adolescents.
Despite the availability of data about drinking frequency and patterns, the surveys on alcohol use among adolescents carried out in Europe tend not to provide information about diagnostic criteria for alcohol use disorders (AUD) or estimation of their prevalence. This study assesses the prevalence of AUD among a sample of Spanish adolescents, to identify the most prevalent symptoms, and explore gender differences in AUD in this population. The final sample consisted of 504 participants aged 15 to 18, obtained by means of random sampling from all the schools in the region of Asturias (Spain). The presence of alcohol abuse (AA) and alcohol dependence (AD) disorders was evaluated according to DSM-IV-TR criteria. The results showed that 12.5% of the sample met the criteria for the diagnosis of AUD (6.7% for alcohol abuse, AA, and 5.8% for alcohol dependence, AD). The most prevalent symptoms were having social problems for AA diagnosis (9% of students who reported alcohol use in the past year) and tolerance for AD diagnosis (45.8% of students who reported alcohol use in the past year). Males showed a significantly higher score than females in AUD, AA and two AA diagnosis criteria (hazardous use and legal problems). The prevalence of AUD among Spanish adolescents is very high, males being more likely than females to endorse criteria for AUD and AA, though not for AD. These findings reveal a serious health issue and highlight the need to develop preventive efforts and provide coordinated alcohol-abuse interventions.


Biological responses of human bone marrow mesenchymal stem cells to Sr-M-Si (M = Zn, Mg) silicate bioceramics.
Strontium (Sr), Zinc (Zn), magnesium (Mg), and silicon (Si) are reported to be essential trace elements for the growth and mineralization of bone. We speculated that the combination of these bioactive elements in bioceramics may be effective to regulate the osteogenic property of bone-forming cells. In this study, two Sr-containing silicate bioceramics, Sr(2)ZnSi(2)O(7) (SZS) and Sr(2)MgSi(2)O(7) (SMS), were prepared. The biological response of human bone marrow mesenchymal stem cells (BMSCs) to the two bioceramics (in the forms of powders and dense ceramic bulks) was systematically studied. In powder form, the effect of powder extracts on the viability and alkaline phosphatase (ALP) activity of BMSCs was investigated. In ceramic disc form, both direct and indirect coculture of BMSCs with ceramic discs were used to investigate their biological response, including attachment, proliferation, ALP activity, and bone-related genes expression. Beta-tricalcium phosphate (β-TCP) and akermanite (Ca(2)MgSi(2)O(7), CMS) were used as control materials. The results showed that the Sr, Zn, and Si (or Sr, Mg, and Si)-containing ionic products from SZS and SMS powders enhanced ALP activity of BMSCs, compared to those from β-TCP. Both SZS and SMS ceramic discs supported the growth of BMSCs, and most importantly, significantly enhanced the ALP activity and bone-related genes expression of BMSCs as compared to β-TCP. The results suggest that the specific combination of bioactive ions (Sr, Zn, Si, e.g.) in bioceramics is a viable way to improve the biological performance of biomaterials, and the form of materials and surface properties were nonnegligible factors to influence cell response.


Wide educational disparities in young adult cardiovascular health.
Widening educational differences in overall health and recent stagnation in cardiovascular disease mortality rates highlight the critical need to describe and understand educational disparities in cardiovascular health (CVH) among U.S. young adults. We use two data sets representative of the U.S. population to examine educational disparities in CVH among young adults (24-34) coming of age in the 21st century: the National Health and Nutrition Examination Survey (2005-2010; N= 689) and the National Longitudinal Study of Adolescent to Adult Health (2007-2008; N=11,200). We employ descriptive statistics and regression analysis. The results show that fewer than one in four young adults had good CVH (at least 5 out of 7 ideal cardiovascular indicators). Young adults who had not attained a college degree demonstrate particularly disadvantaged CVH compared with their college-educated peers. Such educational disparities persist after accounting for a range of confounders, including individuals' genetic propensity to develop coronary artery disease. The results indicate that the CVH of today's young adults is troubling and especially compromised for individuals with lower levels of educational attainment. These results generate substantial concern about the future CVH of the US population, particularly for young adults with a low level of education.


Postoperative Outcome of a New Shoulder Orthesis after Arthroscopic Rotator Cuff Repair: a Prospective, Randomized Observational Study.
Rotator cuff tears are one of the most frequently treated disorders in arthroscopic surgery. Besides the different surgical options, there are differences in the postoperative aftercare. In this observational study the function, handling and comfort of two different ortheses (ADVAGOshoulder vs. standard abduction orthesis) were compared. 53 patients with a rotator cuff tear (n = 25 ADVAGOshoulder, n = 28 standard abduction orthesis) were examined and questioned before and after the surgical treatment based on the DASH Score, a modified Constant Score, the function, handling and everyday practicality of their orthesis. The ADVAGOshoulder orthesis showed favorable results concerning the limitations of daily activity, quality of sleep and limitations in movement. The assessment by the patients regarding the contribution to therapeutic success was also more pronounced with ADVAGOshoulder. The standard abduction orthesis was assessed twice as good as the ADVAGOshoulder orthesis in relation to the overall success of treatment. Regarding the DASH questionnaires no significant differences were seen between the two groups. Both ortheses proved to be a suitable tool for immobilization of the shoulder after surgery, and contributed to the success of treatment, as assessed by the patients. The ADVAGOshoulder orthesis showed advantages related to limitations in movement and quality of sleep compared to the standard abduction orthesis.


Exploring the influence of boundary shapes on emission angular distributions and polarization states of broad-area vertical-cavity surface-emitting lasers.
We design the stadium-shaped and rectangular vertical-cavity surface-emitting lasers (VCSELs) to investigate the influence of boundary shapes on the emission angular distributions and polarization states. For the stadium-shaped VCSELs, the emission angular distribution prefers to be almost omnidirectional because the lasing mode with purely scarred structure is seldom to be excited. On the contrary, the rectangular VCSELs usually generate dominant lasing modes with the morphology of quasi-periodic linear ridges, which can make emission angular distribution to be concentrated on the certain direction. From the polarization-resolved light-current curves, the stadium-shaped VCSEL is quite prone to exhibit numerous abrupt changes (kinks) associated with polarization switching with increasing current, whereas for rectangular VCSEL there is no conspicuous kink to be seen during a wide range of current changing from near to far above lasing threshold.


Analysis of Rehabilitation Occupational Therapy Techniques Based on Instrumental Music Chinese Tonal Language Spectrogram Analysis.
This paper provides an in-depth analysis of timbre-speech spectrograms in instrumental music, designs a model analysis of rehabilitation occupational therapy techniques based on the analysis of timbre-speech spectrograms in instrumental music, and tests the models for comparison. Starting from the mechanism of human articulation, this paper models the process of human expression as a time-varying linear system consisting of excitation, vocal tract, and radiation models. The system's overall architecture is designed according to the characteristics of Chinese speech and everyday speech rehabilitation theory (HSL theory). The dual judgment of temporal threshold and short-time average energy realized the phonetic length training. Tone and clear tone training were achieved by linear predictive coding technique (LPC) and autocorrelation function. Using the DTW technique, isolated word speech recognition was achieved by extracting Mel-scale Frequency Cepstral Coefficients (MFCC) parameters of speech signals. The system designs corresponding training scenes for each training module according to the extracted speech parameters, combines the multimedia speech spectrogram motion situation with the speech parameters, and finally presents the training content as a speech spectrogram, and evaluates the training results through human-machine interaction to stimulate the interest of rehabilitation therapy and realize the speech rehabilitation training of patients. After analyzing the pre- and post-test data, it was found that the p-values of all three groups were <0.05, which was judged to be significantly different. Also, all subjects changed their behavioral data during the treatment. Therefore, it was concluded that the music therapy technique could improve the patients' active gaze communication ability, verbal command ability, and active question-answering ability after summarizing the data, i.e., the hypothesis of this experiment is valid. Therefore, it is believed that the technique of timbre-speech spectrogram analysis in instrumental music can achieve the effect of rehabilitation therapy to a certain extent.