Antiapoptotic herpesvirus Bcl-2 homologs escape caspase-mediated conversion to proapoptotic proteins.
The antiapoptotic Bcl-2 and Bcl-x(L) proteins of mammals are converted into potent proapoptotic factors when they are cleaved by caspases, a family of apoptosis-inducing proteases (E. H.-Y. Cheng, D. G. Kirsch, R. J. Clem, R. Ravi, M. B. Kastan, A. Bedi, K. Ueno, and J. M. Hardwick, Science 278:1966-1968, 1997; R. J. Clem, E. H.-Y. Cheng, C. L. Karp, D. G. Kirsch, K. Ueno, A. Takahashi, M. B. Kastan, D. E. Griffin, W. C. Earnshaw, M. A. Veliuona, and J. M. Hardwick, Proc. Natl. Acad. Sci. USA 95:554-559, 1998). Gamma herpesviruses also encode homologs of the Bcl-2 family. All tested herpesvirus Bcl-2 homologs possess antiapoptotic activity, including the more distantly related homologs encoded by murine gammaherpesvirus 68 (gammaHV68) and bovine herpesvirus 4 (BHV4), as described here. To determine if viral Bcl-2 proteins can be converted into death factors, similar to their cellular counterparts, five herpesvirus Bcl-2 homologs from five different viruses were tested for their susceptibility to caspases. Only the viral Bcl-2 protein encoded by gammaHV68 was susceptible to caspase digestion. However, unlike the caspase cleavage products of cellular Bcl-2, Bcl-x(L), and Bid, which are potent inducers of apoptosis, the cleavage product of gammaHV68 Bcl-2 lacked proapoptotic activity. KSBcl-2, encoded by the Kaposi's sarcoma-associated herpesvirus, was the only viral Bcl-2 homolog that was capable of killing cells when expressed as an N-terminal truncation. However, because KSBcl-2 was not cleavable by caspases, the latent proapoptotic activity of KSBcl-2 apparently cannot be released. The Bcl-2 homologs encoded by herpesvirus saimiri, Epstein-Barr virus, and BHV4 were not cleaved by apoptotic cell extracts and did not possess latent proapoptotic activities. Thus, herpesvirus Bcl-2 homologs escape negative regulation by retaining their antiapoptotic activities and/or failing to be converted into proapoptotic proteins by caspases during programmed cell death.


Efficiency of Nebulizing Furosemide in the Treatment of Chronic Pulmonary Obstructive Disease: A Systematic Review and Meta-Analysis of Clinical Trials.
Chronic obstructive pulmonary disease (COPD) is one of the most common chronic illnesses in humans. Among both oral and intravenous diuretics, nebulizing furosemide (Lasix) is the most commonly used agent. The purpose of this study was to ascertain the therapeutic effects of nebulizing furosemide compared with placebo in the treatment of COPD using a systematic review and meta-analysis of clinical trials. This review was performed based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) protocol. The databases of Web of Science, Google Scholar, PubMed, and Scopus were independently searched by two researchers using MeSH keywords. Studies published between 2002 and 2018 in different parts of the world were considered. The meta-analysis was performed through STATA 14 software and the heterogeneity was assessed using Q statistic or I2 index. From 40 selected articles, 8 articles were finally included in the systematic review process. The analyses were performed considering two groups; nebulizing furosemide treatment (i.e. case) and placebo (i.e. control). Based on the forest plots, the average values of PaCO2 were 48.3 (39.04-57.56) and 46.56 (39.94-53.18) in the case and control groups, respectively. Also, the mean forced expiratory volume in the first second (FEV1) was 49 (31.32-66.67) and 46.87 (31.44-62.30) in the case and control groups, respectively. Meta-regression analysis showed that both heart and pulse rates in the nebulizing furosemide group decreased by increasing the year of study and sample size (P <0.001). The heterogeneity among the studies was found to be 72.2%, which is classified as severe heterogeneity. nebulizing furosemide can improve and normalize the vital signs and other respiratory variables in patients with COPD.


Nucleic acid enzymology of extremely halophilic bacteria. Halobacterium cutirubrum deoxyribonucleic acid-dependent ribonucleic acid polymerase.
1. DNA-dependent RNA polymerase was purified 150-fold from crude extracts of the extreme halophile Halobacterium cutirubrum. 2. The enzyme requires the presence of native DNA and all four nucleoside triphosphates to incorporate (14)C-labelled nucleoside triphosphate into an acid-insoluble ribonuclease-sensitive product. 3. It has an absolute requirement for both Mn(2+) and Mg(2+). 4. The polymerase requires a high salt concentration for stability, but is markedly inhibited by univalent cations. 5. Its molecular weight is very low compared with that of Escherichia coli RNA polymerase.


Survival after an amniotic fluid embolism following the use of sodium bicarbonate.
Amniotic fluid embolism (AFE) is a rare and potentially fatal complication of pregnancy. In this case report, we highlight the successful use of sodium bicarbonate in a patient with an AFE. We present a case of a 38-year-old mother admitted for an elective caesarean section. Following the delivery of her baby, the mother suffered a cardiac arrest. Following a protracted resuscitation, transoesophageal echocardiography demonstrated evidence of acute pulmonary hypertension, with an empty left ventricle and an over-distended right ventricle. In view of these findings and no improvement noted from on-going resuscitation, sodium bicarbonate was infused as a pulmonary vasodilator. Almost instantaneous return of spontaneous circulation was noted, with normalisation of cardiac parameters. We propose that in patients suspected with AFE and who have been unresponsive to advance cardiac life support measures, and where right ventricular failure is present with acidosis and/or hypercarbia, the use of sodium bicarbonate should be considered.


Differential expression of maf-1 and maf-2 genes in the developing rat lens.
To examine the expression of maf-1 and maf-2 protocogenes in the developing rat lens. Maf-1 and maf-2 transcripts were assayed in rat lenses on embryonic days 13 and 16 (E13 and E16) by in situ hybridization using single-stranded RNA probes. Proteins encoded by the maf-2 gene were assayed immunocytochemically in embryonic (E12, 13, 16, 19) and postnatal day 14 and 90 (P14 and P90) lenses. In embryonic lenses, we detected maf-1 messenger RNA (mRNA) in the lens epithelium and maf-2 mRNA diffusely distributed in the lens fiber cells. By immunocytochemistry, Maf-2 was detected on E12 in the nuclei of almost all lens pit cells. On days E13, E16, and E19, however, lens epithelial cells showed no immunoreactivity, but nuclei of fiber cells reacted strongly. On P14, nuclei containing Maf-2 protein were confined to the equator of the lens, but at 3 months of age, no Maf-2 could be detected in the rat lens. Western blotting showed that the anti-Maf-2 antiserum reacted with a single protein, of molecular weight approximately 39 kDa, in rat lens. Results showed the spatial and temporal regulation of maf gene expression and suggest that these genes participate in transcriptional regulation during the development of the lens in the rat.


Using selected scenes from Brazilian films to teach about substance use disorders, within medical education.
Themes like alcohol and drug abuse, relationship difficulties, psychoses, autism and personality dissociation disorders have been widely used in films. Psychiatry and psychiatric conditions in various cultural settings are increasingly taught using films. Many articles on cinema and psychiatry have been published but none have presented any methodology on how to select material. Here, the authors look at the portrayal of abusive use of alcohol and drugs during the Brazilian cinema revival period (1994 to 2008). Qualitative study at two universities in the state of São Paulo. Scenes were selected from films available at rental stores and were analyzed using a specifically designed protocol. We assessed how realistic these scenes were and their applicability for teaching. One author selected 70 scenes from 50 films (graded for realism and teaching applicability > 8). These were then rated by another two judges. Rating differences among the three judges were assessed using nonparametric tests (P < 0.001). Scenes with high scores (> 8) were defined as "quality scenes". Thirty-nine scenes from 27 films were identified as "quality scenes". Alcohol, cannabis, cocaine, hallucinogens and inhalants were included in these. Signs and symptoms of intoxication, abusive/harmful use and dependence were shown. We have produced rich teaching material for discussing psychopathology relating to alcohol and drug use that can be used both at undergraduate and at postgraduate level. Moreover, it could be seen that certain drug use behavioral patterns are deeply rooted in some Brazilian films and groups.


Emotion Differentiation and Youth Mental Health: Current Understanding and Open Questions.
A growing body of research identifies emotion differentiation-the ability to specifically identify one's emotions-as a key skill for well-being. High emotion differentiation is associated with healthier and more effective regulation of one's emotions, and low emotion differentiation has been documented in several forms of psychopathology. However, the lion's share of this research has focused on adult samples, even though approximately 50% of mental disorders onset before age 18. This review curates what we know about the development of emotion differentiation and its implications for youth mental health. I first review published studies investigating how emotion differentiation develops across childhood and adolescence, as well as studies testing relations between emotion differentiation and mental health in youth samples. Emerging evidence suggests that emotion differentiation actually falls across childhood and adolescence, a counterintuitive pattern that merits further investigation. Additionally, several studies find relations between emotion differentiation and youth mental health, but some instability in results emerged. I then identify open questions that limit our current understanding of emotion differentiation, including (i) lack of clarity as to the valid measurement of emotion differentiation, (ii) potential third variables that could explain relations between emotion differentiation and mental-health (e.g., mean negative affect, IQ, personality, and circularity with outcomes), and (iii) lack of clear mechanistic models regarding the development of emotion differentiation and how it facilitates well-being. I conclude with a discussion of future directions that can address open questions and work toward interventions that treat (or even prevent) psychopathology.


Developmental trajectories of childhood disruptive behaviors and adolescent delinquency: a six-site, cross-national study.
This study used data from 6 sites and 3 countries to examine the developmental course of physical aggression in childhood and to analyze its linkage to violent and nonviolent offending outcomes in adolescence. The results indicate that among boys there is continuity in problem behavior from childhood to adolescence and that such continuity is especially acute when early problem behavior takes the form of physical aggression. Chronic physical aggression during the elementary school years specifically increases the risk for continued physical violence as well as other nonviolent forms of delinquency during adolescence. However, this conclusion is reserved primarily for boys, because the results indicate no clear linkage between childhood physical aggression and adolescent offending among female samples despite notable similarities across male and female samples in the developmental course of physical aggression in childhood.


A Guide to Carrying Out a Phylogenomic Target Sequence Capture Project.
High-throughput DNA sequencing techniques enable time- and cost-effective sequencing of large portions of the genome. Instead of sequencing and annotating whole genomes, many phylogenetic studies focus sequencing effort on large sets of pre-selected loci, which further reduces costs and bioinformatic challenges while increasing coverage. One common approach that enriches loci before sequencing is often referred to as target sequence capture. This technique has been shown to be applicable to phylogenetic studies of greatly varying evolutionary depth. Moreover, it has proven to produce powerful, large multi-locus DNA sequence datasets suitable for phylogenetic analyses. However, target capture requires careful considerations, which may greatly affect the success of experiments. Here we provide a simple flowchart for designing phylogenomic target capture experiments. We discuss necessary decisions from the identification of target loci to the final bioinformatic processing of sequence data. We outline challenges and solutions related to the taxonomic scope, sample quality, and available genomic resources of target capture projects. We hope this review will serve as a useful roadmap for designing and carrying out successful phylogenetic target capture studies.


The correlation between Salter's criteria for avascular necrosis of the femoral head and Kalamchi's prognostic classification following the treatment of developmental dysplasia of the hip.
The aim of this study was to evaluate the correlation between Salter's criteria and Kalamchi's classification of avascular necrosis in patients treated for developmental dysphasia of the hip (DDH). The study involved a retrospective analysis of 123 patients (123 hips) with DDH treated by operative and non-operative reduction before the age of two years, with a minimum follow-up of ten years. Salter's criteria (S1 to S4) were determined from radiographs obtained at one to two years post-reduction, whilst the Kalamchi grade was determined from radiographs obtained at ten or more years of age. Early post-reduction radiographs were also used to evaluate the centre-head distance discrepancy (CHDD) and the occurrence of a dome-shaped deformity of the proximal femoral metaphysis (D-shaped metaphysis). The prognosis was described as good (Kalamchi grade K0 or KI), fair (Kalamchi grade KII) or poor (Kalamchi grade KIII or KIV) for analysis and correlation with the early Salter criteria, CHDD and D-shaped metaphysis. S1 and S2 criteria were predictive of a poor prognosis. The outcome following S3, S4 and S3 + S4 varied; 18 (40%) had a good prognosis, 17 (38%) a fair prognosis and ten (22%) a poor prognosis. A CHDD ≥ 10% and a D-shaped metaphysis were also predictive of a poor prognosis. The Salter criteria were predictive of the Kalamchi grade of avascular necrosis in patients with DDH aged ten or more years after reduction of the hip. Cite this article: Bone Joint J 2017;99-B:1115-20.


On measuring selection in experimental evolution.
Distributions of mutation fitness effects from evolution experiments are available in an increasing number of species, opening the way for a vast array of applications in evolutionary biology. However, comparison of estimated distributions among studies is hampered by inconsistencies in the definitions of fitness effects and selection coefficients. In particular, the use of ratios of Malthusian growth rates as 'relative fitnesses' leads to wrong inference of the strength of selection. Scaling Malthusian fitness by the generation time may help overcome this shortcoming, and allow accurate comparison of selection coefficients across species. For species reproducing by binary fission (neglecting cellular death), ln2 can be used as a correction factor, but in general, the growth rate and generation time of the wild-type should be provided in studies reporting distribution of mutation fitness effects. I also discuss how density and frequency dependence of population growth affect selection and its measurement in evolution experiments.


A Ground Truth Based Comparative Study on Detecting Epistatic SNPs.
Genome-wide association studies (GWAS) have been widely applied to identify informative SNPs associated with common and complex diseases. Besides single-SNP analysis, the interaction between SNPs is believed to play an important role in disease risk due to the complex networking of genetic regulations. While many approaches have been proposed for detecting SNP interactions, the relative performance and merits of these methods in practice are largely unclear. In this paper, a ground-truth based comparative study is reported involving 9 popular SNP detection methods using realistic simulation datasets. The results provide general characteristics and guidelines on these methods that may be informative to the biological investigators.


The platelet dense tubular system: its relationship to prostaglandin synthesis and calcium flux.
The platelet dense tubular system, an internal smooth endoplasmic reticulum membrane system occupies a pivotal position in the initiation and modulation of platelet activation. The best available evidence suggests platelet prostaglandin and thromboxane synthesis and an internal calcium store critical to platelet activation are both found in the platelet dense tubular system. Studies of the structural, physiologic and chemical properties of thromboxane A2 support the concept that this product of platelet prostaglandin synthesis acts to carry the calcium from the dense tubular system into the cytoplasm where the calcium is released to initiate contraction of the platelet contractile protein. Evaluation of platelet phospholipase A2 suggests that calcium may be critical to activation of this enzyme. Two of the steps occurring during platelet activation which appear to require calcium 1) phospholipase A2 acting as the critical carrier of calcium from one location to the other.


Levels of chromosomally encoded Umu proteins and requirements for in vivo UmuD cleavage.
Most of the inducible mutagenesis observed in Escherichia coli after treatment with many DNA damaging agents is dependent upon the products of the umuD,C operon. RecA-mediated proteolytic processing of UmuD yields a carboxyl-terminal fragment (UmuD') that is active for mutagenesis. Processing of UmuD is therefore a critical step in the fixation of mutations. In this paper we have analyzed the requirements for UmuD processing in vivo. Standard immuno-detection assays, coupled with a sensitive chemiluminescence detection assay, have been utilized to probe levels of chromosomally encoded Umu proteins from whole-cell E. coli extracts. We found that the derepression of additional SOS gene products, other than RecA, was not required for UmuD processing. Moreover, efficient cleavage of UmuD was observed only in the presence of elevated levels of activated RecA, suggesting that efficient processing would occur only under conditions of severe DNA damage. Detection of chromosomally encoded Umu proteins has allowed us, for the first time, to measure directly the cellular steady-state levels of these proteins under various SOS inducing conditions. UmuD was present at approximately 180 copies per uninduced cell and was measured at approximately 2400 copies per cell in strains that lacked a functional repressor. Induced levels of UmuC were approximately 12-fold lower than UmuD with approximately 200 molecules per cell. These levels of cellular UmuC protein suggest that it functions through specific protein-DNA or protein-protein interactions, possibly as a lesion recognition protein or by interacting with DNA polymerase III.


Cortactin controls cell motility and lamellipodial dynamics by regulating ECM secretion.
Branched actin assembly is critical for both cell motility and membrane trafficking. The branched actin regulator cortactin is generally considered to promote cell migration by controlling leading-edge lamellipodial dynamics. However, recent reports indicate that lamellipodia are not required for cell movement, suggesting an alternate mechanism. Because cortactin also regulates membrane trafficking and adhesion dynamics, we hypothesized that altered secretion of extracellular matrix (ECM) and/or integrin trafficking might underlie motility defects of cortactin-knockdown (KD) cells. Consistent with a primary defect in ECM secretion, both motility and lamellipodial defects of cortactin-KD cells were fully rescued by plating on increasing concentrations of exogenous ECM. Furthermore, cortactin-KD cell speed defects were rescued on cell-free autocrine ECM produced by control cells, but not on ECM produced by cortactin-KD cells. Investigation of the mechanism revealed that whereas endocytosed fibronectin (FN) is redeposited at the basal cell surface by control cells, cortactin-KD cells exhibit defective FN secretion and abnormal FN retention in a late endocytic/lysosomal compartment. Cortactin-KD motility and FN deposition defects were phenocopied by KD in control cells of the lysosomal fusion regulator synaptotagmin-7. Rescue of cortactin-KD cells by expression of cortactin-binding domain mutants revealed that interaction with the Arp2/3 complex and actin filaments is essential for rescue of both cell motility and autocrine ECM secretion phenotypes, whereas binding of SH3-domain partners is not required. Efficient cell motility, promoted by cortactin regulation of branched actin networks, involves processing and resecretion of internalized ECM from a late endosomal/lysosomal compartment.


Mannitol biosynthesis is required for plant pathogenicity by Alternaria alternata.
Mannitol has been hypothesized to play a role in antioxidant defense. In previous work, we confirmed the presence of the two mannitol biosynthetic enzymes, mannitol dehydrogenase (MtDH) and mannitol 1-phosphate 5-dehydrogenase (MPDH), in the fungus Alternaria alternata and created disruption mutants for both enzymes. These mutants were used to investigate the role of mannitol in pathogenicity of A. alternata on its host, tobacco. Conidia of all mutants were viable and germinated normally. GC-MS analysis demonstrated elevated levels of trehalose in the mutants, suggesting that trehalose may substitute for mannitol as a storage compound for germination. Tobacco inoculation showed no reduction in lesion severity caused by the MtDH mutant as compared with wild type; however, the MPDH mutant and a mutant in both enzymes caused significantly less disease. Microscopy analysis indicated that the double mutant was unaffected in the ability to germinate and produce appressoria on tobacco leaves and elicited a defense response from the host, indicating that it was able to penetrate and infect the host. We conclude that mannitol biosynthesis is required for pathogenesis of A. alternata on tobacco, but is not required for spore germination either in vitro or in planta or for initial infection.


Embryonal sarcoma of the liver with chondroid differentiation.
A 31-year-old female complained of upper abdominal and back pain. Laboratory tests showed elevated levels of aspartate aminotransferase, alanine aminotransferase and α-fetoprotein. Computed tomography revealed that the tumor, measuring 14.5 cm × 10.4 cm, occupied the anterior and medial segments of the liver and consisted of multicystic and solid lesions. The preoperative diagnosis was a hepatic cystadenocarcinoma. The operation was performed urgently because of tumor rupture. Histopathologically, spindle and asteroid cells were found to have proliferated diffusely. There were no neoplastic epithelial tumor cells. Tumor cells had periodic acid-Schiff-positive hyalin globules. At the periphery, trapped normal bile duct cells were observed. The final diagnosis was embryonal sarcoma of the liver (ESL). Interestingly, irregular islands of chondrosarcoma-like lesions were found in the tumor and the tumor-associated vascular endothelium showed immunoreactivity for KIT. Two months after the operation, the tumor recurred. At 6 mo follow-up, the patient is alive with the disease and undergoing chemotherapy. This is the first report of ESL with chondroid differentiation.


Outcomes of patients treated with noninvasive ventilation by a medical emergency team on the wards.
Initiation of noninvasive ventilation (NIV) on the wards is not universally accepted. Medical emergency teams (METs) provide acute care and monitoring to deteriorating patients on the general wards. Whether it is safe for an MET to start NIV in ward patients with respiratory distress remains unclear. We evaluated 1,123 MET calls in 30,217 ward patients between January 2009 and June 2011 from the prospectively maintained MET database in our tertiary care hospital. We identified ward patients with acute desaturation (< 90%) and tachypnea (breathing frequency > 28 breaths/min), for whom an MET was called. Subjects transferred to the ICU at the end of an MET call were excluded. The remaining ward subjects were divided into 2 groups: patients who were not started on NIV by the MET; versus patients who were started on NIV by the MET. The primary outcome was endotracheal intubation or ICU transfer within 48 hours of MET activation. Secondary outcome measures were 28-day mortality and ICU mortality. Two hundred thirty-eight MET subjects met the study criteria, and 109 immediate ICU transfers were excluded. Of the remaining 129 ward subjects, 54 were in the NIV group, and 75 in the no-NIV group. The NIV group subjects were sicker (mean Acute Physiology and Chronic Health Evaluation II score 17.6 ± 5.1 versus 14.4 ± 5, P < .001). Subjects with pulmonary edema, COPD exacerbation, or asthma exacerbation were more likely, while those with pneumonia were less likely to be placed on NIV. The primary outcome was reached in 2/54 (3.7%) of the NIV subjects and 12/75 (16%) of the no-NIV subjects (P = .03). There was no significant difference (P > .30) between the groups in 28-day mortality (7.4% vs. 13.3%) or ICU mortality (3.7% vs 8%). In selected ward patients, especially those with COPD or pulmonary edema, NIV can be safely initiated by an MET.


Genetics of vestibular syndromes.
The increased availability of next generation sequencing has enabled a rapid progress in the discovery of genetic variants associated with vestibular disorders. We have summarized molecular genetics finding in vestibular syndromes during the last 18 months. Genetic studies continue to shed light on the genetic background of vestibular disorders. Novel genes affecting brain development and otolith biogenesis have been associated with motion sickness. Exome sequencing has made possible to identify three rare single nucleotide variants in PRKCB, DPT and SEMA3D linked with familial Meniere disease. Moreover, superior canal dehiscence syndrome might be related with variants in CDH3 gene, by increasing risk of its development. On the other hand, the association between vestibular schwannoma and enlarged vestibular aqueduct with variants in NF2 and SLC26A4, respectively, seems increasingly clear. Finally, the use of mouse models is allowing further progress in the development gene therapy for hearing and vestibular monogenic disorders. Most of episodic or progressive syndromes show familial clustering. A detailed phenotyping with a complete familial history of vestibular symptoms is required to conduct a genetic study. Progress in these studies will allow us to understand diseases mechanisms and improve their current medical treatments.


Placebo and nocebo effects and operant pain-related avoidance learning.
Research on learning in placebo and nocebo has relied predominantly on Pavlovian conditioning procedures. Operant learning procedures may more accurately model learning in real-life situations in which placebo and nocebo effects occur. To investigate the development and persistence of placebo and nocebo effects using an operant avoidance learning task. Pain-free participants (n = 58) could learn to avoid pain by performing movements that differed in difficulty and intensity of painful stimulation. Participants performed movements in 2 contexts. In the high cost of avoidance context, pain stimulus intensity reduced with increasing movement difficulty. In the low cost of avoidance context, contingencies were reversed. Participants rated pain expectations and pain intensity. During test, movement difficulties were unchanged, but participants always received a medium-intensity pain stimulus. Placebo and nocebo effects were defined as lower/higher pain intensity ratings for trajectories that previously resulted in low/high-intensity compared with medium-intensity stimulation. As expected, participants acquired differential movement-pain expectations and differential movement choices. Testing with a medium-intensity pain stimulus quickly erased differences in movement choice across contexts, but differences in pain expectations were maintained. Pain modulation across context was in line with movement-pain expectations. However, we only observed placebo effects within the low cost of avoidance context and found no evidence of nocebo effects. Operant learning can change pain expectations, pain modulation, and pain-related avoidance behavior. Persisting pain expectations suggest that acquired pain beliefs may be resistant to disconfirmation, despite self-initiated experience with novel pain-movement contingencies.


Design and tuning of standard additive model based fuzzy PID controllers for multivariable process systems.
This paper describes a design and two-level tuning method for fuzzy proportional-integral derivative (FPID) controllers for a multivariable process where the fuzzy inference uses the inference of standard additive model. The proposed method can be used for any n x n multi-input-multi-output process and guarantees closed-loop stability. In the two-level tuning scheme, the tuning follows two steps: low-level tuning followed by high-level tuning. The low-level tuning adjusts apparent linear gains, whereas the high-level tuning changes the nonlinearity in the normalized fuzzy output. In this paper, two types of FPID configurations are considered, and their performances are evaluated by using a real-time multizone temperature control problem having a 3 x 3 process system.


ATLANTIC DIP: pregnancy outcomes for women with type 1 and type 2 diabetes.
ATLANTIC DIP prospectively evaluated the perinatal and maternal outcomes of pregnancies complicated by Type 1 and Type 2 diabetes during 2006/2007 in 5 antenatal centres. All women with established diabetes for at least 6 months prior to the index pregnancy and booking for antenatal care between 1/1/2006 and 31/12/2007 were included in the study. Results were collected electronically via the DIAMOND Diabetes Information System. Pregnancy outcome was compared with that of the background population receiving antenatal care in the region during the same time. There were 104 singleton pregnancies during the period of study. The stillbirth rate (SBR) of 25/1000 was 5 times greater than that reported in the background population at 5/1000 and the perinatal mortality rate (PMR) of 25/1000 was 3.5 times greater than background 7/1000. The congenital malformation rate (CMR) of 24/1000 was twice that observed in the background population. Women were not well prepared for pregnancy with 28% receiving pre pregnancy care (PPC), 43% receiving pre pregnancy folic acid and 51% achieving a HbA1C < = 7% at first antenatal visit. Pregnancy induced hypertension (PIH) and/or pre eclampsia toxaemia (PET) were three times more common than in women in the background population. In conclusion women are not well prepared for pregnancy. Maternal and infant morbidity and infant mortality are greater in women with diabetes. A regional pre pregnancy care (PPC) programme and centralised glucose management are urgently needed.


Occurrence of potential pathogens in water containing ornamental fishes.
The bacterial population of the water supplied with ornamental fish purchased from retail outlets was examined qualitatively and quantitatively. As many as 10(9) viable aerobic organisms per 100 ml were present, with fecal coliform counts as high as 10(5) per 100 ml. Citrobacter, Escherichia, Pseudomonas, and Vibrio were isolated from 75% or more of the samples, whereas Aeromonas, Alcaligenes, Enterobacter, Flavobacterium, and Streptococcus were isolated from 45 to 65% of the samples. Pseudomonas aeruginosa, Edwardsiella tarda, and Klebsiella pneumoniae were also isolated.


GPCR Signaling Mediates Tumor Metastasis via PI3Kβ.
Inappropriate activation of PI3K signaling has been implicated strongly in human cancer. Although studies on the role of PI3K signaling in breast tumorigenesis and progression have focused most intensively on PI3Kα, a role for PI3Kβ has begun to emerge. The PI3Kβ isoform is unique among class IA PI3K enzymes in that it is activated by both receptor tyrosine kinases and G-protein-coupled receptors (GPCR). In previous work, we identified a mutation that specifically abolishes PI3Kβ binding to Gβγ (p110(526KK-DD)). Expression of this mutant in p110β-silenced breast cancer cells inhibits multiple steps of the metastatic cascade in vitro and in vivo and causes a cell autonomous defect in invadopodial matrix degradation. Our results identify a novel link between GPCRs and PI3Kβ in mediating metastasis, suggesting that disruption of this link might offer a novel therapeutic target to prevent the development of metastatic disease. Cancer Res; 76(10); 2944-53. ©2016 AACR.


Conspecific plant-soil feedbacks of temperate tree species in the southern Appalachians, USA.
Many tree species have seedling recruitment patterns suggesting that they are affected by non-competitive distance-dependent sources of mortality. We conducted an experiment, with landscape-level replication, to identify cases of negative distance-dependent effects and whether variation in these effects corresponded with tree recruitment patterns in the southern Appalachian Mountains region. Specifically, soil was collected from 14 sites and used as inocula in a 62 day growth chamber experiment determining whether tree seedling growth was less when interacting with soil from conspecific (like) than heterospecific (other) tree species. Tests were performed on six tree species. Three of the tree species had been previously described as having greater recruitment around conspecifics (i.e. facilitator species group) compared to the other half (i.e. inhibitor species group). We were then able to determine whether variation in negative distance-dependent effects corresponded with recruitment patterns in the field. Across the six species, none were negatively affected by soil inocula from conspecific relative to heterospecific sources. Most species (four of six) were unaffected by soil source. Two species (Prunus serotina and Tsuga canadensis) had enhanced growth in pots inoculated with soil from conspecific trees vs. heterospecifics. Species varied in their susceptibility to soil pathogens, but trends across all species revealed that species classified as inhibitors were not more negatively affected by conspecific than heterospecific soil inocula or more susceptible to pathogenic effects than facilitators. Although plant-soil biota interactions may be important for individual species and sites, it may be difficult to scale these interactions over space or levels of ecological organization. Generalizing the importance of plant-soil feedbacks or other factors across regional scales may be especially problematic for hyperdiverse temperate forests where interactions may be spatially variable.


Modeling of Tm, Ho:YAG and Tm, Ho:YLF 2- mum Lasers and Calculation of Extractable Energies.
The development of a model for 2-mum laser operation in Tm, Ho:YAG and YLF crystals pumped in the near infrared is reported. This model, based on a simplified spectroscopic scheme, is fitted to a set of characterization experiments by means of three adjustable parameters. Results show that the excited-state populations are predicted with a relative accuracy of approximately 10% for a large range of pump levels. Using this model, we calculate the extractable energy on short-laser-pulse interactions for the two materials under different operation conditions. We study the sensitivity to pump duration and the optimization of dopant concentrations. We investigate the improvement of the extractable-energy efficiency with multiple-pulse operation. For double-pulse operation the improvement is approximately a factor of 1.5 and leads to overall extractable-energy efficiencies of 16% in YAG and 15% in YLF for an absorbed pump energy of 10 J cm(-3).


Biophysical and microbiological study of high hydrostatic pressure inactivation of Bovine Viral Diarrheavirus type 1 on serum.
The effect of high hydrostatic pressure application on fetal bovine serum components and the model microorganism (Bovine Viral Diarrheavirus type 1 NADL strain) was studied at 132 and 220 MPa pressure for 5 min at 25°C. Protein secondary structures were found to be unaffected by an artificial neural network application on the amide I region for both untreated and HHP treated samples. FTIR spectroscopy study of both the HHP-treated and control samples revealed changes in the intensity of some bands in the finger-print region (1500-900 cm(-1)) originating mainly from lipids which are thought to result from changes in the lipoprotein structure. The virus strain lost its infectivity completely after 220 MPa HHP treatments. These results indicate that HHP can be successfully used for inactivation of pestiviruses while leaving structural and functional properties of serum and serum products unaffected.


Hepatic safety of antibiotics used in primary care.
Antibiotics used by general practitioners frequently appear in adverse-event reports of drug-induced hepatotoxicity. Most cases are idiosyncratic (the adverse reaction cannot be predicted from the drug's pharmacological profile or from pre-clinical toxicology tests) and occur via an immunological reaction or in response to the presence of hepatotoxic metabolites. With the exception of trovafloxacin and telithromycin (now severely restricted), hepatotoxicity crude incidence remains globally low but variable. Thus, amoxicillin/clavulanate and co-trimoxazole, as well as flucloxacillin, cause hepatotoxic reactions at rates that make them visible in general practice (cases are often isolated, may have a delayed onset, sometimes appear only after cessation of therapy and can produce an array of hepatic lesions that mirror hepatobiliary disease, making causality often difficult to establish). Conversely, hepatotoxic reactions related to macrolides, tetracyclines and fluoroquinolones (in that order, from high to low) are much rarer, and are identifiable only through large-scale studies or worldwide pharmacovigilance reporting. For antibiotics specifically used for tuberculosis, adverse effects range from asymptomatic increases in liver enzymes to acute hepatitis and fulminant hepatic failure. Yet, it is difficult to single out individual drugs, as treatment always entails associations. Patients at risk are mainly those with previous experience of hepatotoxic reaction to antibiotics, the aged or those with impaired hepatic function in the absence of close monitoring, making it important to carefully balance potential risks with expected benefits in primary care. Pharmacogenetic testing using the new genome-wide association studies approach holds promise for better understanding the mechanism(s) underlying hepatotoxicity.


Early response gene signalling in bryostatin-stimulated primary B chronic lymphocytic leukaemia cells in vitro.
The protein kinase C activator bryostatin induces differentiation and antagonizes the effects of tumour-promoting phorbol esters in a number of different cell types. We show here that bryostatin preferentially inhibits phorbol 12-myristate 13-acetate (PMA)-induced proliferation compared with differentiation in a number of different B chronic lymphocytic leukaemia (BCLL) cell populations examined. By using a panel of 11 early-response gene probes in Northern hybridization analysis, we found that the profile of genes induced in response to bryostatin and PMA was qualitatively similar and displayed comparable sensitivities to inhibition with the serine-threonine kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine hydrochloride (H7), consistent with common signalling through protein kinase C. However, the nuclear oncogene. c-myc, which was induced strongly in response to PMA treatment, was only marginally up-regulated by bryostatin. In addition, bryostatin selectively inhibited the magnitude of PMA-responsive induction of c-myc, to a degree commensurate with its antagonistic effects seen at the biological level. Finally, an anti-sense oligonucleotide blockade of c-myc inhibited PMA-induced proliferation but not the differentiation of BCLL cells, implicating this nuclear oncogene as an important determinant distinguishing PMA from bryostatin-coupled biological responses and also as a candidate third-messenger effector target for the anti-tumour effects of bryostatin.


Blood management in two-stage revision knee arthroplasty for deep prosthetic infection.
Treatment of infected total knee arthroplasty requires aggressive management to treat the infection and restore joint function. For patients with infected knee arthroplasties, a two-stage procedure is used that involves resection of the joint and placement of an antibiotic impregnated cement spacer followed by implantation of a new prosthetic 6 weeks later. Patients undergoing the two-stage procedure typically endure high allogeneic blood transfusion rates (82% to 88%) and progressive anemia because the two surgeries are spaced closely and because the infection precludes the use of alternatives to allogeneic blood. Records were reviewed of 75 patients who underwent two-stage total knee arthroplasty to characterize perioperative hemoglobin levels and blood transfusion needs in this patient group. Although transfusions were administered only when warranted by clinical symptoms and were not based on predetermined hematologic values, 62 (82%) patients received a mean of 2.3 units of blood at first-stage surgery, and 60 (80%) patients received a mean of 2.1 units of blood at the second stage. Overall, only 12% of patients did not have allogeneic blood transfusion. At the first stage before resection, mean hemoglobin concentration was 11.6 g/dL and reached a mean nadir of 8.6 g/dL 3 days after surgery. At the second stage before reimplantation, hemoglobin concentration averaged 11.1 g/dL and reached a mean nadir of 8.2 g/dL 3 days after surgery. After the first stage, allogeneic blood transfusion failed to improve postoperative hemoglobin levels enough to prevent transfusions associated with the second-stage. Patients undergoing two-stage total knee arthroplasty have anemia, and a substantial proportion of these patients require allogeneic blood transfusion at both stages. Thus, novel blood management practices are required to improve hemoglobin levels and reduce allogeneic transfusion rates in this patient population.


Estrogen-induced reactive oxygen species, through epigenetic reprogramming, causes increased growth in breast cancer cells.
Despite the progress made in cancer diagnosis and treatment, breast cancer remains the second leading cause of cancer-related death among the women. Exposure to elevated levels of endogenous estrogen or environmental estrogenic chemicals is an important risk factor for breast cancer. Estrogen metabolites and ROS generated during estrogen metabolism are known to play a critical role in estrogen carcinogenesis. However, the molecular mechanisms through which estrogen-induced ROS regulate gene expression is not clear. Epigenetic changes of DNA methylation and histone modifications are known to regulate genes expression. Therefore, the objective of this study was to evaluate whether estrogen-induced ROS, through aberrant expression of epigenetic regulatory genes and epigenetic reprogramming, causes growth of breast cancer cells. Estrogen responsive MCF-7 and T47D human breast cancer cells were exposed to natural estrogen 17 beta-estradiol (E2) and synthetic estrogen Diethylstilbestrol (DES) both alone and in combination with antioxidant N-acetyl cysteine. Effects of NAC-mediated scavenging of estrogen-induced ROS on cell growth, gene expression, and histone modifications were measured. The result of MTT and cell cycle analysis revealed significant abrogation of E2 and DES-induced growth by scavenging ROS through NAC. E2 and DES caused significant changes in expression of epigenetic regulatory genes for DNA methylation and histone modifications as well as changes in both gene activating and repressive marks in the Histone H3. NAC restored the expression of epigenetic regulatory genes and changes in histone marks. Novel findings of this study suggest that estrogen can induce growth of breast cancer cells through ROS-dependent regulation of epigenetic regulatory genes and epigenetic reprogramming of histone marks.


Impact of cadaveric renal transplantation on survival in patients listed for transplantation.
The aim of this study was to assess the magnitude of the survival benefit of renal transplantation compared with dialysis in patients selected for transplantation in Scotland. Longitudinal study of survival and mortality risk in all adult patients (1732) listed for a first transplant between January 1, 1989, and December 31, 1989, in Scotland. A time-dependent Cox regression analysis adjusted for comorbidity, sociodemographic and geographic factors, primary renal disease, time on dialysis, and year of listing compared the risk of death for patients receiving a first cadaveric transplant versus all patients on dialysis listed for transplantation. After adjustment for the covariates, the relative risk (RR) of death during the first 30 days after transplantation was 1.35 (95% confidence interval [CI], 0.63 to 2.86) compared with patients on dialysis (RR = 1). The long-term RR (at 18 mo) for the transplant recipients was 0.18 (95% CI, 0.08 to 0.42) when compared with patients on dialysis (RR = 1). This lower long-term risk of death was present in all patients undergoing transplantation, irrespective of their age group or primary renal disease. Similar results were seen when survival with a transplant was censored for graft failure. The projected life expectancy with a transplant was 17.19 yr compared with only 5.84 yr on dialysis. Despite an initial higher risk of death, long-term survival for patients who undergo transplantation is significantly better compared with patients who are listed but remain on dialysis. A successful transplant triples the life expectancy of a listed renal failure patient.


Reconceptualizing Measurement of Emergency Contraceptive Use: Comparison of Approaches to Estimate the Use of Emergency Contraception.
Estimated use of emergency contraception (EC) remains low, and one reason is measurement challenges. The study aims to compare EC use estimates using five approaches. Data come from Performance Monitoring and Accountability 2020 surveys from 10 countries, representative sample surveys of women aged 15 to 49 years. We explore EC use employing the five definitions and calculate absolute differences between a reference definition (percentage of women currently using EC as the most effective method) and each of the subsequent four, including the most inclusive (percentage of women having used EC in the past year). Across the 17 geographies, estimated use varies greatly by definition and EC use employing the most inclusive definition is statistically significantly higher than the reference estimate. Impact of using various definitions is most pronounced among unmarried sexually active women. The conventional definition of EC use likely underestimates the magnitude of EC use, which has unique programmatic implications.


Experimental study designs to improve the evaluation of road mitigation measures for wildlife.
An experimental approach to road mitigation that maximizes inferential power is essential to ensure that mitigation is both ecologically-effective and cost-effective. Here, we set out the need for and standards of using an experimental approach to road mitigation, in order to improve knowledge of the influence of mitigation measures on wildlife populations. We point out two key areas that need to be considered when conducting mitigation experiments. First, researchers need to get involved at the earliest stage of the road or mitigation project to ensure the necessary planning and funds are available for conducting a high quality experiment. Second, experimentation will generate new knowledge about the parameters that influence mitigation effectiveness, which ultimately allows better prediction for future road mitigation projects. We identify seven key questions about mitigation structures (i.e., wildlife crossing structures and fencing) that remain largely or entirely unanswered at the population-level: (1) Does a given crossing structure work? What type and size of crossing structures should we use? (2) How many crossing structures should we build? (3) Is it more effective to install a small number of large-sized crossing structures or a large number of small-sized crossing structures? (4) How much barrier fencing is needed for a given length of road? (5) Do we need funnel fencing to lead animals to crossing structures, and how long does such fencing have to be? (6) How should we manage/manipulate the environment in the area around the crossing structures and fencing? (7) Where should we place crossing structures and barrier fencing? We provide experimental approaches to answering each of them using example Before-After-Control-Impact (BACI) study designs for two stages in the road/mitigation project where researchers may become involved: (1) at the beginning of a road/mitigation project, and (2) after the mitigation has been constructed; highlighting real case studies when available.


[Post surgery morbidity in patients with complicated hepatic hydatidosis].
Hepatic echinococcosis (HE) surgery is common in southern's Chile hospitals; however, related publications are scarce and with conflicting results, especially with regard to postoperative morbidity (POM), due to the diversity in it severity. The aim of this study is to determine POM in patients undergoing surgery for complicated HE (CHE). Case series part of a prospective cohort. Patients undergoing surgery for CHH in hospitals Hernán Henríquez Aravena hospital and Clínica Mayor of Temuco, between 2000 and 2012 were included. The main outcome variable was development of POM using the Clavien scale. Other variables of interest were hospital stay, mortality and recurrence. Descriptive statistics were applied and incidence of POM was determined. 73 patients with a median age of 41 years and 58.9% female were studied. The median ultrasound diameter cysts were 15.0 cm. The average surgical time was 125.4 ± 26.3 min. The surgical procedure used most often was the pericystectomy (84.9%); and 84.9% of cases was performed concomitantly some other surgical procedure. The incidence of POM was 19.2%, 78.6% of whose cases were Grade I or II Clavien. The aetiology was 10.9% of medical complications and 8.2% of surgical complications. 1.4% of mortality was recorded; and with a median follow up of 97 months, no recurrence was verified. POM in a cohort of patients with CHE is lower than the published and low severity. Subgroups with higher POM were: patients with coexistence of more than one complication, those with colangiohydatidosis and patients with liver abscess of hydatid origin.


[Hopeless and unbearable suffering and deliberate ending of life of newborn infants].
Deliberate ending of life of newborns is an extreme measure that is usually based on hopeless and existing unbearable suffering. There are currently developments that may lead to clarification and refinement of the standards and rules surrounding deliberate ending of life of newborns. This pertains to the phase immediately following the decision to refrain from curative treatment. An important aspect here is that parents and doctors will have to reach agreement on the extent to which the suffering of the newborn can be classified as unbearable. Furthermore, in the case of deliberate ending of life of newborns, consideration must be given not only to current suffering but also the severe suffering that will develop in the near future. The points ofspecial importance that the medical profession had developed in relation to the assessment of future unbearable suffering may provide assistance here and should be implemented.


Ferric and cobaltous hydroacid complexes for forward osmosis (FO) processes.
Cupric and ferric hydroacid complexes have proven their advantages as draw solutes in forward osmosis in terms of high water fluxes, negligible reverse solute fluxes and easy recovery (Ge and Chung, 2013. Hydroacid complexes: A new class of draw solutes to promote forward osmosis (FO) processes. Chemical Communications 49, 8471-8473.). In this study, cobaltous hydroacid complexes were explored as draw solutes and compared with the ferric hydroacid complex to study the factors influencing their FO performance. The solutions of the cobaltous complexes produce high osmotic pressures due to the presence of abundant hydrophilic groups. These solutes are able to dissociate and form a multi-charged anion and Na(+) cations in water. In addition, these complexes have expanded structures which lead to negligible reverse solute fluxes and provide relatively easy approaches in regeneration. These characteristics make the newly synthesized cobaltous complexes appropriate as draw solutes. The FO performance of the cobaltous and ferric-citric acid (Fe-CA) complexes were evaluated respectively through cellulose acetate membranes, thin-film composite membranes fabricated on polyethersulfone supports (referred as TFC-PES), and polybenzimidazole and PES dual-layer (referred as PBI/PES) hollow fiber membranes. Under the conditions of DI water as the feed and facing the support layer of TFC-PES FO membranes (PRO mode), draw solutions at 2.0 M produced relatively high water fluxes of 39-48 LMH (L m(-2) hr(-1)) with negligible reverse solute fluxes. A water flux of 17.4 LMH was achieved when model seawater of 3.5 wt.% NaCl replaced DI water as the feed and 2.0 M Fe-CA as the draw solution under the same conditions. The performance of these hydroacid complexes surpasses those of the synthetic draw solutes developed in recent years. This observation, along with the relatively easy regeneration, makes these complexes very promising as a novel class of draw solutes.


Early itch relief with upadacitinib predicts later skin clearance in Atopic dermatitis.
Though Janus kinase inhibitors such as upadacitinib rapidly relieve itch in atopic dermatitis (AD) patients, how early itch relief impacts later skin clearance is not examined. This study aims to determine if early itch relief by upadacitinib could predict complete skin clearance in later phases. This retrospective study involved 105 patients with moderate-to-severe AD treated with upadacitinib 15 mg/day. Eczema area and severity index (EASI), atopic dermatitis control tool, and achievement rate of EASI 100 were evaluated at weeks 4, 12, and 24. The threshold of early peak pruritus-numerical rating scale (PP-NRS) predicting later skin clearance was assessed by area under the receiver-operating characteristic curve, and predictors for EASI 100 achievement were determined by logistic regression analysis. The rate of achieving EASI 100 at week 24 was extremely higher in patients who achieved week 2 PP-NRS ≤ 1 (42.9%) than in non-achievers (1.4%). The logistic regression analysis showed that the achievement of week 2 PP-NRS ≤ 1 and low body mass index were associated with achievement of EASI 100 at weeks 12 and 24. The achievement of week 2 PP-NRS ≤ 1 may predict later skin clearance in upadacitinib treatment.


Spot distribution measurement using a scanning nanoslit.
A scanning and rotating nanoslit is used to measure submicrometer features in focused spot distributions. Using a filtered backprojection technique, a highly accurate reconstruction is demonstrated. Experimental results are confirmed by simulating the scanning slit technique using a physical optics simulation program. Analysis of various error mechanisms is reported, and the reconstruction algorithm is determined to be very resilient. The slit is 125 nm wide and 50 μm long and is fabricated on a 120 nm thick layer of aluminum. The size of the image field is 15 μm, and simulations indicate that 200 nm Rayleigh resolution is possible with an infinitely narrow slit.


Memantine attenuates the impairment of spatial learning and memory of pentylenetetrazol-kindled rats.
Cognitive disorders after epilepsy can have a great impact on the quality of life of epileptic patients, though it has not drawn much attention. Even after identified, it is often undertreated or has gone untreated. Memantine has been approved to treat moderate to severe Alzheimer disease (AD), which is characterized by cognitive impairment. In present study, we determined the effects of memantine on PTZ-kindled rats, which can mimic the postseizure dysfunction that resembles symptoms observed in human epilepsy. We found that memantine can ameliorate the spatial learning and memory of epileptic rats. But contrary to previous claims that memantine can improve cognition in AD patients, without serious side effects on normal learning and memory abilities, we found that rats treated only with memantine exhibited the impaired spatial learning and memory ability. We conclude that memantine can improve cognition related to an excitotoxicity-induced pathologic state, but the potential side effects of memantine on the physiological processes should be considered.


Phosphorylation of calponin in airway smooth muscle.
Calponin is an actin-binding protein known to be a substrate in vitro for several protein kinases and phosphoprotein phosphatases. We tested the hypothesis that calponin is phosphorylated in vivo using canine tracheal smooth muscle strips metabolically labeled with 32Pi. Calponin was gel purified from muscles stimulated with 1 microM carbachol. Phosphorylation increased to 2.0 times the basal level of 178 +/- 26 counts per minute (cpm)/microgram calponin within 30 s to 350 +/- 64 cpm/micrograms. Two-dimensional nonequilibrium pH gradient gel electrophoresis resolved four charge isoforms of calponin in unstimulated muscle. Stimulation with carbachol induced an additional more acidic isoform. Phosphorylation of calponin in vitro with protein kinase C (PKC) also induced formation of additional acidic isoforms. The functional effect of phosphorylation was demonstrated using an in vitro motility assay in which unphosphorylated calponin (2 microM) caused a profound inhibition of actin sliding. Calponin phosphorylated by PKC did not inhibit actin sliding. The results show that phosphorylation of calponin occurs in intact tracheal smooth muscle and that phosphorylation of calponin in vitro alleviates the inhibitory effect of calponin on actomyosin function.


Whitefly resistance traits derived from the wild tomato Solanum pimpinellifolium affect the preference and feeding behavior of Bemisia tabaci and reduce the spread of Tomato yellow leaf curl virus.
Breeding of tomato genotypes that limit whitefly (Bemisia tabaci) access and feeding might reduce the spread of Tomato yellow leaf curl virus (TYLCV), a begomovirus (genus Begomovirus, family Geminiviridae) that is the causal agent of tomato yellow leaf curl disease. TYLCV is restricted to the phloem and is transmitted in a persistent manner by B. tabaci. The tomato breeding line ABL 14-8 was developed by introgressing type IV leaf glandular trichomes and secretion of acylsucroses from the wild tomato Solanum pimpinellifolium accession TO-937 into the genetic background of the whitefly- and virus-susceptible tomato cultivar Moneymaker. Results of preference bioassays with ABL 14-8 versus Moneymaker indicated that presence of type IV glandular trichomes and the production of acylsucrose deterred the landing and settling of B. tabaci on ABL 14-8. Moreover, electrical penetration graph studies indicated that B. tabaci adults spent more time in nonprobing activities and showed a reduced ability to start probing. Such behavior resulted in a reduced ability to reach the phloem. The superficial type of resistance observed in ABL 14-8 against B. tabaci probing significantly reduced primary and secondary spread of TYLCV.


Investigation of organophilic montmorillonite clay inclusion in zearalenone-contaminated diets using the mouse uterine weight bioassay.
Previous studies with low-pH montmorillonite (LPHM) clay exchanged with alkylammonium compounds showed that these organo clays were quite effective in sorbing the estrogenic mycotoxin zearalenone (ZEN) from aqueous solution. The potential toxicity of these types of clays, in particular hexadecyltrimethylammonium (HDTMA) LPHM, led to the investigation of the sorption efficacy of clay exchanged with a less toxic primary amine analog, hexadecylamine (HDA). Isothermal analysis studies showed that HDA LPHM was able to bind ZEN, but less effectively than HDTMA LPHM as evidenced by a significantly lower Freundlich K (63,900 vs. 845). The in vivo effectiveness of these two clays to bind ZEN was tested utilizing the mouse uterine weight bioassay. At a dietary inclusion level of 0.25%, the clays did not have a negative impact on overall animal health as measured by final body weight; however, they did not protect the animals from the estrogenic effects induced by 35 mg ZEN/kg in the feed (i.e., the uterine weights were not reduced in comparison to ZEN alone). In fact, the HDTMA LPHM group showed an increase in uterine weight that was more than the ZEN treatment group. When the animals were fed 0.5% clay, both exchanged clays (i.e., HDTMA LPHM and HDA LPHM) resulted in decreased body weight gain. The uterine weights of ZEN-fed animals (either alone or in combination with clays) were not significantly different from each other. In contrast, the uterine:body weight ratio showed a dramatic increase in the groups fed exchanged clay + ZEN compared to ZEN alone. These results suggest that alkylamine groups may assist the transport or uptake of ZEN and result in an enhanced toxicity from contaminated feed. The findings from this study clearly demonstrate the need for careful testing of all mycotoxin-binding agents before their inclusion in the diet.


Utrophin mRNA Expression in Muscle Is Not Restricted to the Neuromuscular Junction.
Utrophin is normally present exclusively in synaptic regions of skeletal muscle fibers, although it is expressed extrasynaptically in certain pathological situations, where it has been proposed to compensate for the absence of dystrophin in Duchenne muscular dystrophy patients and mdx mice. Recently there have been conflicting reports regarding the preferential expression of utrophin mRNA at the neuromuscular junction. Using in situ hybridization with RNA probes, we show a clear accumulation of autoradiographic labeling at more than 90% of neuromuscular junctions (identified by histochemical demonstration of cholinesterase activity). The intensity of this labeling is proportional to the number of junctional myonuclei in the section. Some clusters of labeling were found associated with nonmuscle nuclei (e.g., blood vessels, nerves), where utrophin is present. In addition, labeling for utrophin mRNA was associated with about 25% of extrajunctional myonuclei, where the protein is not present. The mean labeling per nucleus at junctional myonuclei was at least 10 times greater than at extrajunctional myonuclei. We discuss the possible regulatory mechanisms involved in the heterogeneous expression of utrophin mRNA in skeletal muscle. Copyright 1998 Academic Press.


The family stress and support inventory (FSSI).
The Family Stress and Support Inventory (FSSI) is a new self-report family assessment instrument that is theoretically grounded in sociological and family stress theory and designed to provide a brief, reliable, valid, quantifiable, and global assessment of the intrafamilial stress and support variables. With reference to clearly defined constructs, the respondents rate on a continuum of 1-10 the amount of stress and support that they feel from each individual family member. Scale analysis and psychometric evaluation were completed on a randomly selected sample of 382 people chosen from family practice clinics throughout Minnesota and the University of Minnesota faculty and staff. The test-retest correlations are r = .78, p = .00 for the FSSI Support scale, and r = .68, p = .00 for the FSSI Stress scale. Correlation with social desirability is negligible (r = -.01, p = ns for FSSI Support; r = .11, p = .02 for FSSI Stress). The FSSI Stress scale demonstrates moderately high concurrent validity with the Family Inventory of Life Events and Changes (FILE), another family stress measure (r = .50, p = .00), indicating that both assess similar, but not identical, family stress dimensions. The correlation between the FSSI Support scale and the Family Inventory of Resources for Management (FIRM), another measure of family resources, however, was only r = .10, p = .05, indicating that these two measures evaluate different family support dimensions. The FSSI has many potential applications in family medicine research and clinical care where the intrafamilial stress and support variables must be quantified.


The vitrophage in ocular reconstruction following trauma.
We propose a technique using the Peyman vitrophage, a vitrectomy instrument, for the surgical repair of acute and chronic injuries to the anterior segment, such as perforating corneal injuries and complications of cataract extractions. A pars plana approach allows insertion of the vitrophage into the eye with minimal surgical manipulation. All lens, iris, and vitreous remnants are completely removed. We have achieved excellent results in cases of severe eye injuries.


Chemical parameters, antimicrobial activities, and tissue toxicity of 0.1 and 0.5% sodium hypochlorite solutions.
ffe chemical parameters, antimicrobial activity, and tissue toxicity of two sodium hypochlorite (NaOCl) solutions buffered to a physiologic pH were studied. Initially, a 0.5% NaOCl solution buffered with 3 g of NaH2PO4 per liter was examined. The solution had a pH of 7.49 and an osmolality of 352 mOsmol/liter. When compared with unbuffered and NaHCO3-buffered 0.5% NaOCl solutions, the NaH2PO4-buffered solution was significantly more effective in killing Staphylococcus aureus in vitro. However, the pH of the NaH2PO4-buffered solution decreased over time with a concomitant decrease in antibacterial activity. A freshly prepared solution decontaminated human cadaveric skin colonized by S. aureus, Pseudomonas aeruginosa, or Candida albicans in vitro within 10 min of exposure, whereas a 24-h-old solution cleared the skin of organisms within 15 min. When gauze soaked with 0.5% NaOCl was applied to guinea pig skin for 2 weeks, a 15% decrease in basal cell viabilities was noted. Because of the pH instability and basal cell toxicity, a 0.1% NaOCl solution buffered with NaH2PO4-Na2HPO4 was evaluated. This solution had an osmolality of 386 mOsmol/liter and a pH of 7.4 that was stable over 1 week. A freshly prepared 0.1% NaOCl solution decontaminated skin colonized with S. aureus, C. albicans, and P. aeruginosa within 10, 20, and 30 min, respectively. A 24-h-old solution did not completely decontaminate the colonized skin but significantly reduced the number of microorganisms on the skin surface (P less than 0.001). Application of this solution of guinea pig skin for 2 weeks produced no significant effect on basal cell viabilities. These solutions may serve as alternative topical agents for use in burn therapy.


Differential sensitization to deoxyribonuclease I of Xenopus vitellogenin and albumin genes during primary and secondary induction of vitellogenesis by oestradiol.
The sensitivity to DNAase (deoxyribonuclease) I (which preferentially digests transcribed sequences) of vitellogenin and albumin genes in liver and erythrocytes of male Xenopus after primary and secondary induction of vitellogenesis by oestrogen was measured by hybridization to cDNA (complementary DNA) of the residual DNA after enzymic digestion of isolated nuclei. Vitellogenin sequences were rendered selectively more sensitive to limited DNAase-I digestion (15-20% of DNA rendered acid-soluble) during primary hormonal activation (5 days) of vitellogenin genes in liver, but not erythrocyte, nuclei. Hormone withdrawal (25 days after first injection) did not result in reversion to a pre-activation gene configuration, nor did secondary hormonal stimulation (5 days after second and 25 days after first injection) augment the sensitivity of the genes to digestion by the nuclease. Similar hormone treatment did not affect the sensitivity of the constitutively expressed albumin genes in liver nuclei, nor their insensitivity in erythrocyte nuclei. Under the same conditions, globin genes remained indigestible in liver nuclei. It is concluded that primary induction of vitellogenesis in male Xenopus liver is accompanied by relatively long-lasting (3-4 weeks) change in the configuration of vitellogenin genes in hepatic nuclei which is not reversed or further modified during short-term oestrogen withdrawal or upon secondary stimulation.


[Surgical treatment of laryngotracheal stenoses. Our experience].
Laryngo-tracheal stenoses (LTS) treatment is a problem of difficult management for the otolaryngologist. There are many and varied techniques in order to solve the conundrum. The aim of this article is to analyze retrospectively the outcomes of surgical treatment of LTS in our Institution. We have checked 11 cases (9 men and 2 women, arithmetic mean 30.7 years) operated through surgical procedures during a 6 years lapse of time. All patients were endotracheally intubated prior the stenosis appearance. Stenosis location most encountered were subglottic-tracheal combination. To the end of the study 44 percent of the series was successfully cured and the 33 percent only partially recovered. The employed techniques (endoscopic or open surgery) are revised at the light of today's literature.


Long-term high-fat-diet feeding impairs mitochondrial biogenesis in liver of male and female rats.
Mitochondrial biogenesis includes both mitochondrial proliferation and differentiation and its regulation under different physiological conditions is not clear. Given the sexual dimorphism previously found in mitochondrial function, the aim of this study was to investigate the gender-dependent effect of chronic high-fat-diet (HFD) feeding on rat liver mitochondrial function and biogenesis. Ten-week old male and female rats were fed a HFD (26% fat) or a control diet (2.9% fat) for 26 weeks. Mitochondrial morphology was studied. Mitochondrial DNA and protein content, hydrogen peroxide production, oxidative capacity, antioxidant defenses, as well as markers of oxidative damage and mitochondrial biogenesis were analyzed. Female rats showed higher levels of mitochondrial protein and an enhanced oxidative capacity per mitochondrion than males. In both genders, HFD feeding increased mtDNA content and decreased mitochondrial differentiation markers. In comparison to male rats, females show higher oxidative capacity as a consequence of their greater mitochondrial differentiation under both control and obese status. In response to HFD feeding, the oxidative capacity of the whole mitochondrial population is maintained in both genders. This is obtained by means of an enhancement of mitochondrial proliferation, which counteracts the diet-induced impairment of the function of each mitochondrion.


Molecular cloning, gene structure and expression profile of two mouse peroxisomal 3-ketoacyl-CoA thiolase genes.
In rats, two peroxisomal 3-ketoacyl-CoA thiolase genes (A and B) have been cloned, whereas only one thiolase gene is found in humans. The aim of this study was thus to clone the different mouse thiolase genes in order to study both their tissue expression and their associated enzymatic activity. In this study, we cloned and characterized two mouse peroxisomal 3-ketoacyl-CoA thiolase genes (termed thiolase A and B). Both thiolase A and B genes contain 12 exons and 11 introns. Using RNA extracted from mouse liver, we cloned the two corresponding cDNAs. Thiolase A and B cDNAs possess an open reading frame of 1272 nucleotides encoding a protein of 424 amino acids. In the coding sequence, the two thiolase genes exhibited approximately equal to 97% nucleotide sequence identity and approximately equal to 96% identity at the amino acid level. The tissue-specific expression of the two peroxisomal 3-ketoacyl-CoA thiolase genes was studied in mice. Thiolase A mRNA was mainly expressed in liver and intestine, while thiolase B mRNA essentially exhibited hepatic expression and weaker levels in kidney, intestine and white adipose tissue. Thiolase A and B expressions in the other tissues such as brain or muscle were very low though these tissues were chiefly involved in peroxisomal disorders. At the enzymatic level, thiolase activity was detected in liver, kidney, intestine and white adipose tissue but no significant difference was observed between these four tissues. Moreover, thiolase A and B genes were differently induced in liver of mice treated with fenofibrate. Two mouse thiolase genes and cDNAs were cloned. Their corresponding transcripts are mostly expressed in the liver of mice and are differently induced by fenofibrate.


Poly(ethylene glycol)-based ionic liquids: properties and uses as alternative solvents in organic synthesis and catalysis.
PEG-based ionic liquids are a new appealing group of solvents making the link between two distinct but very similar fluids: ionic liquids and poly(ethylene glycol)s. They find applications across a range of innumerable disciplines in science, technology, and engineering. In the last years, the possibility to use these as alternative solvents for organic synthesis and catalysis has been increasingly explored. This Review highlights strategies for their synthesis, their physical properties (critical point, glass transition temperature, density, rheological properties), and their application in reactions catalyzed by metals (such as Pd, Cu, W, or Rh) or as organic solvent (for example for multicomponent reactions, organocatalysis, CO2 transformation) with special emphasis on their toxicity, environmental impact, and biodegradability. These aspects, very often neglected, need to be considered in addition to the green criteria usually considered to establish ecofriendly processes.


Design and storage stability of reference materials for microfluidic quantitative PCR-based equine gene doping tests.
One method of gene doping in horseracing is administering of exogenous genetic materials, known as transgenes. Several polymerase chain reaction (PCR)-based methods have been developed for detecting transgenes with high sensitivity and specificity. However, novel designs for reference materials (RMs) and/or positive template controls (PTCs) are necessary for simultaneous analysis of multiple transgene targets. In this study, we designed and developed a novel RM for simultaneously detecting multiple targets via microfluidic quantitative PCR (MFQPCR). Twelve equine genes were selected as targets in this study. A sequence region including primers and probes for quantitative PCR was designed, and a 10 bp sequence was inserted to allow the RM to be distinguished from the original transgene sequences. The sequences of individual detection sites were then connected for 12 genes and cloned into a single plasmid vector. We performed fragment size analysis to distinguish between the PCR products of the original transgene sequence and those of the RM, enabling identification of RM contamination. PTCs diluted to 10,000, 1,000, 100, and 10 copies/µl with horse genomic DNA from RM were stably stored at 4°C for 1 year. As digital PCR enabled absolute quantification, the designed substances can serve as an RM. These findings indicate that the RM design and storage conditions were suitable for gene doping tests using MFQPCR.


Unbiased proteomic and transcript analyses reveal that stathmin-1 silencing inhibits colorectal cancer metastasis and sensitizes to 5-fluorouracil treatment.
Colorectal cancer metastasis is a major cause of mortality worldwide, which may only be controlled with novel methods limiting tumor dissemination and chemoresistance. High stathmin-1 (STMN1) expression was previously established as a hallmark of colorectal cancer progression and predictor of poor survival; however, the mechanism of action is less clear. This work demonstrates that STMN1 silencing arrests tumor-disseminative cascades by inhibiting multiple metastatic drivers, and repressing oncogenic and mesenchymal transcription. Using a sensitive iTRAQ labeling proteomic approach that quantified differential abundance of 4562 proteins, targeting STMN1 expression was shown to reinstate the default cellular program of metastatic inhibition, and promote cellular adhesion via amplification of hemidesmosomal junctions and intermediate filament tethering. Silencing STMN1 also significantly improved chemoresponse to the classical colorectal cancer therapeutic agent, 5FU, via a novel caspase-6 (CASP6)-dependent mechanism. Interestingly, the prometastatic function of STMN1 was independent of p53 but required phosphorylations at S25 or S38; abrogating phosphorylative events may constitute an alternative route to achieving metastatic inhibition. These findings establish STMN1 as a potential target in antimetastatic therapy, and demonstrate the power of an approach coupling proteomics and transcript analyses in the global assessment of treatment benefits and potential side-effects. Stathmin-1 is a potential candidate in colorectal cancer therapy that targets simultaneously the twin problems of metastatic spread and chemoresistance.


Antidepressant-associated mood elevations in bipolar II disorder compared with bipolar I disorder and major depressive disorder: a systematic review and meta-analysis.
Antidepressant-associated manic and hypomanic episodes have been reported in bipolar I disorder but are rare in major depressive disorder (MDD). Several lines of evidence suggest that bipolar II disorder is a distinct illness from bipolar I disorder and MDD. The risk of antidepressant-associated mood elevations (AAME) in bipolar II disorder relative to bipolar I disorder and MDD is unknown. We conducted a computer-aided MEDLINE search encompassing the dates 1949 to February 2008, using the keywords antidepressant and mania, antidepressant and hypomania, antidepressant and bipolar, fluoxetine and bipolar, fluvoxamine and bipolar, sertraline and bipolar, paroxetine and bipolar, citalopram and bipolar, escitalopram and bipolar, venlafaxine and bipolar, mirtazapine and bipolar, bupropion and bipolar, monoamine oxidase inhibitor and bipolar, phenelzine and bipolar, tranylcypromine and bipolar, tricyclic and bipolar, imipramine and bipolar, amitriptyline and bipolar, nortriptyline and bipolar, and desipramine and bipolar. All prospective English-language studies, including randomized, controlled trials (RCTs), open-label studies, and naturalistic treatment reports, were eligible for inclusion. We located 13 studies, including 7 RCTs, that reported rates of antidepressant-associated mood elevations in bipolar I disorder versus bipolar II disorder, and 5, including 4 RCTs, that reported rates in bipolar II disorder versus MDD. Data were combined to estimate mean switch rates and subjected to meta-analysis to determine the relative risks of antidepressant-associated mood elevations in bipolar I disorder versus bipolar II disorder and in bipolar II disorder versus MDD. The mean rates of antidepressant-associated mood elevations in studies comparing bipolar I disorder and bipolar II disorder were 14.2% and 7.1%, respectively, in acute trials (less than 16 weeks), and 23.4% and 13.9%, respectively, in maintenance studies. The mean rates in reports comparing bipolar II disorder and MDD were 8.1% and 1.5%, respectively, in acute trials, and 16.5% and 6.0%, respectively, in maintenance studies. The relative risk (RR) of antidepressant-associated mood elevations was greater in bipolar I disorder than bipolar II disorder (RR = 1.78, 95% CI = 1.24 to 2.58, p = .002), and higher in bipolar II disorder than MDD (RR = 2.77, 95% CI = 1.26 to 6.09, p = .01). Mood elevations occurred almost exclusively into hypomania in MDD and bipolar II disorder, while patients with bipolar I disorder experienced manias and hypomanias with similar frequencies. The risk of antidepressant-associated mood elevations in bipolar II disorder is intermediate between that in bipolar I disorder and MDD.


TAS49--a dispersed repetitive sequence isolated from subtelomeric regions of Nicotiana tomentosiformis chromosomes.
We have isolated and characterized a new repetitive sequence, TAS49, from terminal restriction fragments of Nicotiana tomentosiformis genomic DNA by means of a modified vectorette approach. The TAS49 was found directly attached to telomeres of N. tabacum and one of its ancestors, N. tomentosiformis, and also at inner chromosome locations. No association with telomeres was detected neither in N. otophora nor in the second tobacco ancestor, N. sylvestris. PCR and Southern hybridization reveal similarities in the arrangement of TAS49 on the chromosomes of 9 species of the genus Nicotiana, implying its occurrence as a subunit of a conserved complex DNA repeat. TAS49 belongs to the family of dispersed repetitive sequences without features of transposons. The copy number of TAS49 varies widely in the genomes of 8 species analyzed being lowest in N. sylvestris, with 3300 copies per diploid genome. In N. tomentosiformis, TAS49 forms about 0.56% of the diploid genome, corresponding to 17400 copies. TAS49 units are about 460 bp long and show about 90% of mutual homology, but no significant homology to DNA sequences deposited in GenBank and EMBL. Although genomic clones of TAS49 contain an open reading frame encoding a proline-rich protein similar to plant extensins, no mRNA transcript was detected. TAS49 is extensively methylated at CpG and CpNpG sites and its chromatin forms nucleosomes phased with a 170 +/- 8 bp periodicity.


Design of nanocatalysts for green hydrogen production from bioethanol.
Bioethanol is an interesting feedstock that may be used for hydrogen production by steam or autothermal reforming. However, the impurities (heavy alcohols, esters, acids, N compounds) contained in the raw feedstock require a costly purification, as they have a dramatic impact on catalyst activity and stability. Thus, a method that can utilize the raw feedstock without severe degradation of the catalyst would be desirable. In this Minireview, the composition of bioethanol from first and second generation biomass, the reactions involved in the catalytic ethanol steam reforming process and the design of catalysts adapted for hydrogen production from a real bioethanol feed are surveyed.


Evaluation of new version of Mecbio hip resurfacing prosthesis.
The aim of this preliminary study was to compare clinical outcomes of the modern version of the Mecbio resurfacing arthroplasty prosthesis which is custom-designed for each patient with the older prototype which has three sizes. Between 2003 and 2008, 20 patients with hip disorders who underwent a total of 21 arthroplasties with the modern version or prototype prosthesis were included in the study. The prototype was used for the first 15 procedures, while the modern version was used for the last six procedures. The modified lateral approach was performed on all patients. Clinical and radiological examination were also performed by two experienced surgeons. Cortical changes of the calcar were evaluated by comparison of the thinner layer of the medial cortex with thickened one within 5 cm below the lesser trochanter. The patients were also clinically evaluated by the Harris Hip Score. The mean follow-up was three years (range, 2 to 5 years). There was a significant improvement in the Harris Hip Score following surgery compared to baseline between the groups (p<0.05). There was a significant increase in the prototype group (0.14±0.06 to 0.23±0.07, p<0.0001) and modern version group (0.15±0.07 to 0.25±0.03, p=0.0020) in terms of the thinner cortex and thickened cortex in the prototype group (0.21±0.06 to 0.28±0.06 p<0.0001) and modern version group (0.25±0.07 to 0.29±0.05, p=0.0156). There was no significant difference in terms of radiological measurements between the groups. The results suggest that excellent clinical and radiological outcomes can be obtained with both the prototype and modern version prosthesis.


An overview of wideband immittance measurements techniques and terminology: you say absorbance, I say reflectance.
This article reviews the relationships among different acoustic measurements of the mobility of the tympanic membrane, including impedance, admittance, reflectance, and absorbance, which the authors group under the rubric of immittance measures. Each of these quantities is defined and related to the others. The relationship is most easily grasped in terms of a straight rigid ear canal of uniform area terminated by a uniform middle ear immittance placed perpendicular to the long axis of the ear canal. Complications due to variations from this geometry are discussed. Different methods for measuring these quantities are described, and the assumptions inherent within each method are made explicit. The benefits of wideband measurements of these quantities are described, as are the benefits and limitations of different components of immittance and reflectance/absorbance. While power reflectance (the square of the magnitude of pressure reflectance) is relatively invariant along the length of the ear canal, it has the disadvantage that it ignores phase information that may be useful in assessing the presence of acoustic leaks in ear-canal measurements and identifying other potential error sources. A combination of reflectance and impedance magnitude and angle give a more complete description of the middle ear from measurements in the ear canal.


A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies).
Galactokinase deficiency is an inborn error in the first step of galactose metabolism. Its major clinical manifestation is the development of cataracts in the first weeks of life. It has also been suggested that carriers of the deficiency are predisposed to presenile cataracts developing at age 20-50 years. Newborn screening data suggest that the gene frequency is very low worldwide but is higher among the Roma in Europe. Since the cloning of the galactokinase gene (GK1) in 1995, only two disease-causing mutations, both confined to single families, have been identified. Here we present the results of a study of six affected Romani families from Bulgaria, where index patients with galactokinase deficiency have been detected by the mass screening. Genetic linkage mapping placed the disease locus on 17q, and haplotype analysis revealed a small conserved region of homozygosity. Using radiation hybrid mapping, we have shown that GK1 is located in this region. The founder Romani mutation identified in this study is a single nucleotide substitution in GK1 resulting in the replacement of the conserved proline residue at amino acid position 28 with threonine (P28T). The P28T carrier rate in this endogamous population is approximately 5%, suggesting that the mutation may be an important cause of early childhood blindness in countries with a sizeable Roma minority.


Perception of family sense of coherence among Chinese couples with infertility.
To explore perceptions of family sense of coherence among infertile couples and to provide a theoretical interpretation of the comprehensibility, manageability and meaningfulness of couples' experiences coping with infertility. Infertility is a devastating experience for many couples and can have long-lasting psychosocial consequences. Family sense of coherence has the potential to facilitate a couple's adjustment to the life crisis of infertility and may provide a useful conceptual lens to understand experiences of infertility. Sixty-four couples with infertility participated in semi-structured interviews at subfertility clinics. Data were analysed using the constant comparative approach of grounded theory. COREQ guidelines were followed in reporting the study. Three major themes related to infertility emerged from the interviews: comprehensibility, manageability and meaningfulness. The couples experienced psychological strain while making cognitive sense of infertility. The significance of children, which is embedded in traditional Chinese culture, created a sense of meaning and purpose in couples' lives and motivated them to mobilise both internal and external resources to cope with the demands of infertility and its treatment. The findings indicate that the salutogenic model of family sense of coherence can contribute to our understanding of the experiences of infertility among Chinese couples. The results offer a theoretical framework that healthcare professionals can use to help couples cope with the life crisis of infertility by strengthening their sense of family coherence.


[Design of stimulating agents of non-specific resistance system].
The paper briefly reviews a study on the design of drugs enhancing the body's nonspecific resistance to pathogenic agents. To examine the potential regulatory effects on cytokine function was a main trend. The interferon inductor ridostin, dsRNA of microbiological origin, cytokines, as well as the recombinant probiotic strain yielding interferon alpha-2 synthesis were used as a pharmacological agent. This was shown by using a wide range of experimental models wherein these preparations activated the components of the non-specific resistance system resulting in the host's increased capacity to eliminate invasive agents and transformed cells.


Atlantoaxial Langerhans cell histiocytosis radiographic characteristics and corresponding prognosis analysis.
Langerhans cell histiocytosis (LCH) may affect atlas and axis, and there were very few published cases describing a characteristic of LCH of atlantoaxial. The objective of the study is to investigate the image manifestations of atlantoaxial LCH to improve the in-depth comprehension on it. A retrospective study was done of computed tomography (CT) and magnetic resonance imaging in atlas and axis and prognosis was analyzed. The study included 41 patients (average age 12.9 years and median age 8 years) diagnosed with LCH, with 75.6% under 15 years old. Eighty-four lesions of LCH were identified including 47 in the atlas and 37 in the axis. The osteolytic bone destructions in the atlas and axis were characterized, 22% accompanied by sclerotic margins. Thirteen patients had a compression fracture, 11 in the lateral mass of the atlas and 2 in the C2 vertebral body. Sixteen and three patients had atlantoaxial malalignment and dislocation, respectively. On T2-weighted images, 68.9% showed iso- or low-signal intensity, 27.6% showed hyperintensity signal, and 3.4% showed heterogeneous signal. On postcontrast images, 81.9% showed significant enhancement, 12.5% showed moderate enhancement, and 6.3% showed mild enhancement. CT reexamination of 14 patients indicated atlantoaxial bone destruction relatively repaired in 12 patients. Thirty-three patients were a follow-up, 81.8% had no significant symptoms and 18.2% with remaining symptoms. The atlas and axis were affected by LCH, mainly in children. The lateral mass was easily affected and compressed, destruction of the atlas and axis could lead to atlantoaxial joint instability. The prognosis was good in most of the patients.


miR340 suppresses the stem-like cell function of glioma-initiating cells by targeting tissue plasminogen activator.
Glioma-initiating cells (GIC) have stem-like cell properties thought to be sufficient for recurrence, progression, and drug resistance in glioblastomas. In the present study, we defined miRNA (miR)-340 as a differentially expressed miRNA in human GICs that inhibit GIC-mediated tumorigenesis. Furthermore, we defined tissue plasminogen activator (PLAT) as a critical direct target of miR340 for inhibition. Among miRNAs screened, we found that miR340 expression was decreased in all human GICs and in human glioblastoma tissues, compared with human neural stem cells and normal brain tissues. miR340 overexpression in GICs suppressed their proliferative, invasive, and migratory properties in vitro, triggering cell senescence in vitro and inhibiting GIC-induced tumorigenesis in mouse brains. shRNA-mediated silencing of PLAT in GICs phenocopied the effects of miR340 overexpression in vitro and in vivo, suggesting a potential role for tissue factor in stem-like cell function. Taken together, our results identified miR340 as a tumor suppressor that functions in GIC to enforce PLAT blockade and ablate their stem-like functions.


T-lymphocyte subsets, functional deficits, and morphology in sciatic nerves during experimental allergic neuritis.
Conduction velocities, demyelination, "macrophage/dendritic" cells, different sets of T-lymphocytes, and immunoglobulins were estimated in sciatic nerves during various phases of experimental allergic neuritis in Lewis rats. Demyelination was minimal day 15 postimmunization (p.i.) when conduction velocity already was reduced, somewhat more pronounced day 17 p.i. when nerve conduction was blocked, and most pronounced day 23 p.i. when nerve conduction partially had recovered. This suggests a dissociation between the degree of demyelination and the functional deficits. Decrease of sciatic nerve conduction velocities coincided with endoneurial appearance of T-lymphocytes and "macrophage/dendritic" cells, as well as endoneurial immunoglobulins, day 15 p.i. Later partial functional recovery occurred in parallel with the disappearance of T-cells. The degree of functional deficits thus correlated with the number of endoneurial T-lymphocytes. T-cells may, directly or indirectly, initiate several of the disease components in experimental allergic neuritis, including the nerve conduction deficit.


Richer than previously probed: An application of 1H NMR reveals one hundred metabolites using only fifty microliter serum.
The classical approach restricts the detection of metabolites in serum samples by using nuclear magnetic resonance (NMR) spectroscopy; however, the presence of copious proteins and lipoproteins emphasize and necessitate the development of a contemporary, high-throughput tactic. To eliminate the lipoproteins and proteins from sera to engender filtered sera (FS), the study was executed with 50 μl serum obtained from five healthy individuals with 5 years of age difference from 25 to 45 years old and the application of a unique mechanical filter with molecular weight cut-off value of 2KDa. The 10 μl FS from each individual was pooled to make 50 μl final volume filled in a co-axial tube for acquisition of a battery of 1D/2D investigations at 800 MHz NMR spectrometer and the assigned metabolites was confirmed through mass spectrometry as well as by comparing 1H NMR spectra of individual metabolites. This innovative tactic is commissioning to reveal more than 100 metabolites. In contrast to the protein precipitation method, 24 new metabolites were recognized in the present study. The present innovative approach characterizes nucleosides, nitrogenous bases, and volatile metabolites that possibly produce a landmark for the delineation of a comprehensive metabolic profile applicable for detection of the molecular cause of pathogenicity, early-stage disease detection and prognosis, inborn error of metabolism, and forensic investigations exerting the least volume of FS and NMR spectroscopy. The assignment of 100 metabolites using 1H NMR-based FS is described for the first time in the present report.


11C-Methionine PET/CT in patients with primary hyperparathyroidism and inconclusive pre-operative imaging work-up: diagnostic accuracy and role of semi-quantitative analysis.
11C-Methionine PET/CT (C-MET) is a promising method in detecting abnormal parathyroid glands in patients with primary hyperparathyroidism (PHPT). The first aim of the study was to evaluate which is the diagnostic role of C-MET in patients with PHPT and inconclusive pre-operative imaging. Second, we aimed to investigate whether C-MET semi-quantitative parameters may reflect biochemical and histological characteristics of involved glands. Patients with PHPT, undergoing C-MET after an inconclusive pre-operative imaging and having a parathyroid surgery, were retrospectively included. C-MET visual and semi-quantitative assessment was performed. Parameters, as SUVmax, SUVpeak, SUVmean, functional lesion volume (FLV) and total lesion activity (TLA), were measured for each detected lesion; SUVmean, FLV and TLA were calculated on 40-90% thresholds of SUVmax to define SUVmean40-90, FLV40-90 and TLA40-90, respectively. Results were correlated with patients' clinical-laboratory (calcium and PTH values) and histological data (size and weight of excised glands). Mann-Whitney test was used and P value < 0.05 was considered significant. Thirty-eight patients (36 female, age: 57.69 ± 15.13 years) were included. Pre-operative median calcium and PTH values were 11.1 mg/dl [interquartile range (IQR) 10.6-11.5] and 154.6 pg/ml (IQR 101.8-227.0), respectively. C-MET showed a parathyroid uptake in 30 out of thirty-eight patients (78.9%). Among 42 nodules excised, C-MET correctly detected the side of the neck (right/left) in 30/42 with sensitivity, specificity and accuracy of 79, 75 and 79%, respectively. C-MET correctly identified the exact position (superior/inferior) in 27/42 with sensitivity, specificity and accuracy of 75, 50 and 71%, respectively. SUVpeak, FLV50-70 and TLA40-70 were significantly (P < 0.05) higher in patients with higher PTH results. The histological size resulted significantly (P < 0.05) higher in abnormal glands with higher SUVmax, SUVpeak, FLV40-80 and TLA40-90, the weight was higher in glands with higher SUVpeak, SUVmean40-50, FLV40-80 and TLA40-90. C-MET showed a good performance in detecting hyperfunctioning parathyroid glands in PHPT patients with inconclusive pre-operative imaging. Semi-quantitative PET-derived parameters closely correlated with PTH as well as with size and weight of the excised gland, thus reflecting some biochemical and histological characteristics of involved glands.