Spatiotemporal sensitivity of mesoderm specification to FGFR signalling in the Drosophila embryo.
Development of the Drosophila embryonic mesoderm is controlled through both internal and external inputs to the mesoderm. One such factor is Heartless (Htl), a Fibroblast Growth Factor Receptor (FGFR) expressed in the mesoderm. Although Htl has been extensively studied, the dynamics of its action are poorly understood after the initial phases of mesoderm formation and spreading. To begin to address this challenge, we have developed an optogenetic version of the FGFR Heartless in Drosophila (Opto-htl). Opto-htl enables us to activate the FGFR pathway in selective spatial (~ 35 μm section from one of the lateral sides of the embryo) and temporal domains (ranging from 40 min to 14 h) during embryogenesis. Importantly, the effects can be tuned by the intensity of light-activation, making this approach significantly more flexible than other genetic approaches. We performed controlled perturbations to the FGFR pathway to define the contribution of Htl signalling to the formation of the developing embryonic heart and somatic muscles. We find a direct correlation between Htl signalling dosage and number of Tinman-positive heart cells specified. Opto-htl activation favours the specification of Tinman positive cardioblasts and eliminates Eve-positive DA1 muscles. This effect is seen to increase progressively with increasing light intensity. Therefore, fine tuning of phenotypic responses to varied Htl signalling dosage can be achieved more conveniently than with other genetic approaches. Overall, Opto-htl is a powerful new tool for dissecting the role of FGFR signalling during development.


High-Performance Lead-Free Piezoceramics with High Curie Temperatures.
A bismuth ferrite and barium titanate solid solution compound can achieve good piezoelectric properties with a high Curie temperature when fabricated with low-temperature sintering followed by a water-quenching process, with no complicated grain alignment processes performed. By adding the super-tetragonal bismuth gallium oxide to the compound, the piezoelectric properties are as good as those of lead zirconate titanate ceramics.


Repeated neonatal handling with maternal separation permanently alters hippocampal GABAA receptors and behavioral stress responses.
Increasing evidence suggests that postnatal events, such as handling or maternal separation, can produce long-term changes in brain function. These are often expressed as changes in the profile of endocrine or behavioral responses to stress. Changes in gamma-aminobutyric acid type A receptors (GABARs), which mediate the majority of fast synaptic inhibition in adult brain, have been proposed as one potential mediator of these behavioral effects. In the current article, we use a combination of single-cell electrophysiology and antisense mRNA amplification to demonstrate permanent molecular and functional differences in GABARs within hippocampal dentate granule neurons after as few as two episodes of neonatal handling with brief maternal separation. Adult animals that as pups experienced handling with maternal separation maintained a more immature GABAR phenotype and exhibited increased activity in response to swim stress. These findings demonstrate the exquisite sensitivity of the developing GABAergic system to even subtle environmental manipulations and provide an unique molecular mechanism by which postnatal handling with maternal separation may alter stress-related behavior.


[Determination of trace perchlorate in groundwater by solid phase extraction-ion chromatography].
A comprehensive analytical method based on solid phase extraction-ion chromatography (SPE-IC) has been developed for the determination of trace perchlorate in groundwater. An amount of 0.7 liter of groundwater was enriched by a solid phase extraction column after pretreatment to remove the interference ions and then the column was eluted by 6 mL 1% NaOH solution. After filtration of the concentrated liquor with a filter membrane (0.45 microm), the liquor was analyzed on an ion chromatograph (IC) equipped with an Ion Pac AS20 separation column and a 50 microL injection loop, eluted with 40 mmol/L KOH solution. The method detection limit (MDL) and limit of determination (LOD) of perchlorate were 0.15 microg/L and 0.60 microg/L, respectively. The recovery was in the range of 99.7%-100.5% when the sampling concentrations were in the range of 1-15 microg/L. The method is economical and effective. It can be applied to determine trace perchlorate in groundwater. The perchlorate in groundwater samples got from the areas surrounding Harbin was determined by this method. The relative errors were in the range of 1.85%-9.24% between the results got by the SPE-IC and ion chromatography-tandem single quadrupole mass spectrometry.


Direct observation of f-pair magnetic field effects and time-dependence of radical pair composition using rapidly switched magnetic fields and time-resolved infrared methods.
A rapidly switched (<10 ns) magnetic field was employed to directly observe magnetic fields from f-pair reactions of radical pairs in homogeneous solution. Geminate radical pairs from the photoabstraction reaction of benzophenone from cyclohexanol were observed directly using a pump-probe pulsed magnetic field method to determine their existence time. No magnetic field effects from geminate pairs were observed at times greater than 100 ns after initial photoexcitation. By measuring magnetic field effects for fields applied continuously only after this initial geminate period, f-pair effects could be directly observed. Measurement of the time-dependence of the field effect for the photolysis of 2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone in cyclohexanol using time-resolved infrared spectroscopy revealed not only the presence of f-pair magnetic field effects but also the ability of the time dependence of the MARY spectra to observe the changing composition of the randomly encountering pairs throughout the second order reaction period.


Regular vs ad-lib albuterol for patients hospitalized with acute asthma.
Inhaled, short-acting beta-agonists and systemic corticosteroids form the mainstay of therapy in acute asthma exacerbation. Asthma, however, is an inflammatory disease of the airways, and its underlying pathology is not impacted by short-acting beta-agonists. While the efficacy of ad-lib beta-agonist administration in outpatient management of asthma symptoms is well established, little data exist to support this strategy in patients with acute, severe asthma. We postulate that as long as patients hospitalized with severe asthma exacerbation receive systemic corticosteroids, regular, scheduled administration of short-acting beta-agonists is unnecessary. Similar therapeutic outcomes can be achieved with the ad-lib administration of the short-acting beta-agonists. Prospective, randomized, double-blind, placebo-controlled trial. Pulmonary floor of a 600-bed municipal hospital. Sixty-two patients hospitalized for acute asthma. Patients were randomized to receive either albuterol nebulizations (regular albuterol group) or saline solution nebulizations (ad-lib group) every 4 h with management of breakthrough symptoms with albuterol metered-dose inhaler or nebulizations for both groups. All patients received systemic corticosteroids. Peak expiratory flows, asthma symptoms, and need for rescue bronchodilator were followed up on each patient until discharge. There was no significant difference in the length of hospitalization (median length, 48 h for ad-lib group vs 57.5 h for regular albuterol group, p = 0.82), rate of improvement in peak flow, or symptoms between the two groups. Ad-lib beta-agonist use compared to regular albuterol scheduled use resulted in a significant reduction in the total number of albuterol treatments administered (median, 7 treatments vs 19 treatments, p = 0.001) during hospitalization. In the management of asthma exacerbation, ad-lib administration of albuterol is therapeutically as effective as regular, scheduled administration. This method of drug administration also reduces the total dose of beta-agonists received by the hospitalized patient.


The role of message frame, perceived risk, and ambivalence in individuals' decisions to become organ donors.
The decision to become an organ donor involves considering both self-relevant risks and the needs of others. This study applied prospect theory to examine how news exemplar message frames that focus on the possible survival or death of a potential organ transplant recipient affect participants' willingness to become organ donors. Perceived personal risk and ambivalence were examined as moderating variables. Results indicate that risk, rather than ambivalence, played an instrumental role in participants' decisions to donate. Although no main effects or interactions related to message frame emerged in initial analyses, a supplemental analysis revealed an interaction such that there was a modest persuasive advantage for the loss-framed message among low-risk participants. Findings suggest that vivid exemplar message frames, compared to other types of more explicit organ donor appeals, may be associated with unique decisions about organ donation.


Polonium-210 budget in cigarettes.
Due to the relatively high activity concentrations of (210)Po and (210)Pb that are found in tobacco and its products, cigarette smoking highly increases the internal intake of both radionuclides and their concentrations in the lung tissues. That might contribute significantly to an increase in the internal radiation dose and in the number of instances of lung cancer observed among smokers. Samples of most frequently smoked fine and popular brands of cigarettes were collected from those available on the Egyptian market. (210)Po activity concentrations were measured by alpha spectrometry, using surface barrier detectors, following the radiochemical separation of polonium. Samples of fresh tobacco, wrapping paper, fresh filters, ash and post-smoking filters were spiked with (208)Po for chemical recovery calculation. The samples were dissolved using mineral acids (HNO(3), HCl and HF). Polonium was spontaneously plated-out on stainless steel disks from diluted HCl solution. The (210)Po activity concentration in smoke was estimated on the basis of its activity in fresh tobacco and wrapping paper, fresh filter, ash and post-smoking filters. The percentages of (210)Po activity concentrations that were recovered from the cigarette tobacco to ash, post-smoking filters, and smokes were assessed. The results of this work indicate that the average (range) activity concentration of (210)Po in cigarette tobacco was 16.6 (9.7-22.5) mBq/cigarette. The average percentages of (210)Po content in fresh tobacco plus wrapping paper that were recovered by post-smoking filters, ash and smoke were 4.6, 20.7 and 74.7, respectively. Cigarette smokers, who are smoking one pack (20 cigarettes) per day, are inhaling on average 123 mBq/d of (210)Po and (210)Pb each. The annual effective doses were calculated on the basis of (210)Po and (210)Pb intake with the cigarette smoke. The mean values of the annual effective dose for smokers (one pack per day) were estimated to be 193 and 251 microSv from (210)Po and (210)Pb, respectively.


Parents' labour market participation as predictor of children's well-being: changes from 1984 to 1996 in the Nordic countries.
This study analysed the influence of parents' labour market participation on their children's well-being in the five Nordic countries, and the changes from 1984 to 1996, during which unemployment rates generally rose in the Nordic countries. Parent-reported questionnaire data from two cross-sectional studies, 12 years apart, with 15,354 (in 1984) and 15,255 (in 1996) randomly selected children aged 2-17 years. The response rates were 67.0% (n=10290) and 67.6% (n=10317), respectively. The parents' assessment of their children's well-being was measured by six items, with three items focusing on psychological functioning and three items on social functioning. The association between parents' labour market participation and children's well-being changed from 1984 to 1996. In 1984, more children in families with paid work had low well-being than did children in families without paid work. In 1996, however, the share of children with low well-being was higher among children in families without paid work. This change was most notable in Finland but did not occur in Denmark. The overall level of well-being among children in the Nordic countries remained stable over this period. The relationship between parents' labour market participation and well-being among children changed from 1984 to 1996. In 1984 low well-being was most common among children in families with paid work, while in 1996 low well-being was more common in families without participation in the labour market. Social inequality in children's well-being thus increased if parents' labour market participation was used as an indicator of socioeconomic status.


Effect of metal conditioners on the adhesive bonding of resin cements to cast titanium.
To assess the effect of metal conditioners on the bond strength between resin cements and cast titanium. Commercially pure titanium (99.56%) was cast using an arc casting machine. Surfaces were finished with 400-grit silicon carbide paper followed by air abrasion with 50-Microm aluminum oxide. A piece of double-coated tape with a 4-mm circular hole was then positioned on the metal surface to control the area of the bond. The prepared surfaces were then divided into 4 groups (n=10): G1, unprimed Panavia F; G2, Alloy Primer-Panavia F; G3, unprimed Bistite DC; G4, Metaltite-Bistite DC. Forty minutes after insertion of the resin cements, the specimens were detached from the mold and stored in water at 37 degrees C for 24 hours. Shear bond strength was performed in a testing machine (MTS 810) at a crosshead speed of 0.5 mm/min. Data were analyzed using ANOVA and Tukey's test with a .05 significance level. The fractured surfaces were observed through an optical microscope at 103 magnification. The G1 group demonstrated significantly higher shear bond strength (17.95 MPa) than the other groups. G3 (13.79 MPa) and G4 (12.98 MPa) showed similar mean values to each other and were statistically superior to G2 (9.31 MPa). Debonded surfaces generally presented adhesive failure between metal surfaces and resin cements. While the Metaltite conditioner did not influence the bond strength of the Bistite DC cement, the Alloy Primer conditioner significantly decreased the mean bond strength of the Panavia F cement.


Aspirin for cardioprotection and strategies to improve patient adherence.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in North America. Aspirin therapy has proven clinical effectiveness in the prevention and treatment of CVD and is one of the most widely used drugs nationwide. However, despite the medication's popularity and utility, adherence to a proper aspirin regimen is suboptimal, resulting in adverse health outcomes and increased health care costs. Our review outlines current knowledge on aspirin therapy adherence, causes of nonadherence, and strategies available to increase adherence to aspirin and medications in general. We demonstrate that, indeed, aspirin adherence rates are suboptimal, ranging from 72% to 92%, and that a combination of patient- and medication-related factors contribute to nonadherence. A multidimensional approach involving patient education and medication innovations to reduce aspirin side effects is imperative to improving rates of aspirin therapy adherence.


Other Pathologies Were Rarely Reported after Laparoscopic Surgery for Suspected Appendicitis: A Systematic Review and Meta-Analysis.
Diagnostic laparoscopy is often used when a patient is suspected of having acute appendicitis. The aim of this study was to assess the rate of other pathologies found during diagnostic laparoscopy for suspected acute appendicitis. This systematic search included studies with ≥100 patients who received laparoscopy for suspected acute appendicitis and reported on the histopathologic and other intra-abdominal findings. We performed a meta-analysis estimating the rate of other pathologies, and a sensitivity analysis excluding smaller cohorts (≤500 patients). Age groups, sex, specific findings, and geographic regions were investigated. Certainty of evidence was assessed with GRADE. A total of 27 studies were included covering 25,547 patients and of these 793 had an unexpected pathology. The findings were benign pathology in the appendix (34%), malignancy (30%), gynecologic pathology (5%), gastrointestinal pathology (4%), or unspecified (27%). Meta-analysis showed an overall rate of unexpected findings of 3.5% (95% CI 2.7-4.3; moderate certainty), and the sensitivity analysis showed similar results. Malignancy found in the appendix when treating suspected acute appendicitis was 1.0% (95% CI 0.8-1.3%; high certainty). The rate of other histopathological findings in patients with suspected acute appendicitis was low and a malignancy in appendix was found in 1% of patients.


Hand and Arm Bimanual Intensive Therapy Including Lower Extremity (HABIT-ILE) in Children With Unilateral Spastic Cerebral Palsy: A Randomized Trial.
Intensive bimanual training results in more improvement in hand function in children with unilateral spastic cerebral palsy (USCP) than lower intensity conventional interventions. However, it is not known whether combined upper and lower extremity training in an intensive protocol is more efficacious for upper and lower functional abilities than conventional therapies provided in usual customary care. To determine the efficacy of Hand and Arm Bimanual Intensive Therapy Including Lower Extremity (HABIT-ILE) for children with USCP. Twenty-four children with USCP were randomized into 2 groups: an immediate HABIT-ILE group (IHG, initially receiving HABIT-ILE, 10 days = 90 hours), and a delayed HABIT-ILE group (DHG), which continued their conventional/ongoing treatment for an intended total duration of 90 hours. In phase 2, children in the DHG were crossed over to receive HABIT-ILE and children of the IHG were followed in their ongoing conventional therapy. Children were assessed using the Assisting Hand Assessment (AHA, primary outcome), the ABILHAND-Kids, and the Pediatric Evaluation of Disability Inventory. Dexterity (Box and Blocks Test [BBT]) and pinch strength were also measured. Locomotor abilities were assessed with Six-Minute Walk Test (6MWT, primary outcome) and ABILOCO-kids. Social participation was measured with the Assessment of Life-HABITs. A 2 (groups) × 3 (test sessions) analysis of variance indicated significant improvements for primary outcomes (AHA, P < .001; 6MWT, P = .002) and all secondary assessments except BBT, step length and bodyweight distribution following HABIT-ILE, but not conventional therapy. The findings suggest that combined upper and lower extremity in an intensive training protocol may be efficacious for improving both upper and lower extremity function in children with USCP.


Transcriptional regulation of the Pseudomonas aeruginosa type III secretion system.
Type III secretion systems (T3SS) function by translocating effector proteins into eukaryotic host cells and are important for the virulence of many Gram-negative bacterial pathogens. Although the secretion and translocation machineries are highly conserved between different species, each pathogen translocates a unique set of effectors that subvert normal host cell physiology to promote pathogenesis. The uniqueness of each pathogen is further reflected in the diversity of mechanisms used to regulate T3SS gene expression. Pseudomonas aeruginosa utilizes a complex set of signalling pathways to modulate T3SS expression in response to extracellular and intracellular cues. Whereas some pathways are dedicated solely to regulating the T3SS, others co-ordinately regulate expression of the T3SS with multiple virulence functions on a global scale. Emerging regulatory themes include coupling of T3SS transcription with type III secretory activity, global regulatory control through modulation of cAMP biosynthesis, repression by a variety of stresses, involvement of multiple two component regulatory systems, and an inverse relationship between T3SS expression and multicellular behaviour. Factors controlling activation of T3SS expression likely contribute to the environmental survival of the organism and to the pathogenesis of acute P. aeruginosa infections. Conversely, active repression of the T3SS might contribute to the persistence of chronic infections.


Dyslipidemia as a risk factor for coronary disease in patients with diabetes.
To highlight the frequency of lipid abnormalities in patients with diabetes and the need for appropriate treatment strategies for coronary disease. The epidemiologic features of coronary artery disease in the diabetic population are reviewed, and the pathogenesis of atherosclerotic disease is discussed. Various risk factors for predicting coronary artery disease and guidelines for therapeutic intervention are presented. The American Diabetes Association has estimated that 60% of all adults will die of coronary artery disease and that 80% of patients with diabetes will ultimately have atherosclerosis. The accelerated rate of atherosclerosis in patients with diabetes may be attributable to several factors, including hyperglycemia and insulin resistance. Abnormalities in lipid metabolism have a major role in the development of coronary disease. Because the National Cholesterol Education Program guidelines for treatment were established for less complicated hyperlipidemias, The American Diabetes Association recommends more aggressive lipid-lowering therapy at a lower level of low-density lipoproteins (130 mg/dL or 3.36 mmol/L) to produce an equivalent reduction in risk of coronary disease in patients with diabetes. In patients with diabetes, lipid levels should be aggressively reduced to decrease the possibility of coronary artery disease.


Genetic Variants of the FADS Gene Cluster Are Associated with Erythrocyte Membrane LC PUFA Levels in Patients with Mild Cognitive Impairment.
Long-chain (> 20 C-atoms) polyunsaturated fatty acids (LC PUFAs) of both the omega-6 (n-6) and omega-3 (n-3) series are important for the functional integrity of brain and thereby cognition, memory and mood. Clinical studies observed associations between altered LC PUFA levels and neurodegenerative diseases such as Alzheimer´s disease and its prodromal stage, mild cognitive impairment (MCI). The present study examined the LC PUFA status of MCI patients with specific view on the relative LC n-3 PUFA levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes (omega-3 index). 12 single nucleotide polymorphisms (SNPs) of the FADS1, FADS2, and FADS3 gene clusters were genotyped in 111 MCI patients and evaluated associations with PUFA levels in erythrocyte membranes (primary outcome). In addition, the associations between FADS SNPs and LC PUFA levels with serum lipid levels as well as depressive symptoms were examined (secondary outcomes). Minor allele carrier of rs174546, rs174548 (FADS1), rs3834458, rs1535, rs174574, rs174575, rs174576, and rs174578 (FADS2) showed significant higher n-6 and n-3 precursor PUFA levels (linoleic acid, and alpha-linolenic acid, respectively) and lower arachidonic acid (AA) levels in erythrocyte membranes compared to the major allele carriers. Differences in EPA and DHA levels were not significant. Minor allele carriers of rs174574, rs174576 and rs174578 (FADS2) and rs174455 (FADS3) exhibited significant higher triglyceride levels, whereas minor allele carriers for rs174449 and rs174455 (FADS3) exhibited significant higher total- and LDL-cholesterol levels compared to the more common variant. The mean omega-3 index of the study cohort was 6.19 ± 1.55 %. In more than 85 % of the patients, the omega-3 index was below 8 % and in 23 % below 5 %. Moreover, it was shown that a low DHA status and omega-3 index was associated with depressive symptoms (Beck's depression-inventory). These findings indicate an association between several FADS genotypes for higher n-6 and n-3 precursor PUFA and lower AA levels in erythrocyte membranes in minor compared to major allele carriers. To what extent FADS genotypes and a lower conversion of LA and ALA to biologically important LC PUFAs such as AA, EPA and DHA contributes to cognitive decline should be investigated in further trials. Nevertheless, the omega-3 index in this cohort of MCI patients can be classified as insufficient.


Combination of anxiety and depression is associated with an increased headache frequency in migraineurs: a population-based study.
Although anxiety and depression have been classified as distinct traits of affective disorders, previous studies have reported their co-occurrence in subjects with migraine. However, few reports are available on the clinical implications of this comorbidity. This study is to assess the comorbidity of anxiety and depression in subjects with migraine and its clinical implications in a population-based sample from Korea. We selected Korean subjects aged 19-69 years by the stratified random sampling method, and evaluated them using a semi-structured interview, designed to identify headache type, anxiety, and depression. We used Goldberg Anxiety Scale questions and Patient Health Questionnnaire-9 for the diagnosis of anxiety and depression, respectively. Of the 2,762 participants who completed the interview, 147 subjects (5.4%) were classified as having a migraine during the previous year. Among these 147 subjects, 17 (11.6%) had anxiety and depression, 28 (19.0%) had anxiety alone, 9 (6.1%) had depression alone, and 93 (63.3%) had neither anxiety nor depression. Headache frequency per month was remarkably higher in subjects having migraine with anxiety and depression (median [25-75 percentile values], 8.0 [2.5-21.0]) than in those having migraine with anxiety alone (2.0 [1.0-5.0], p = 0.003), migraine with depression alone (1.0 [0.3-4.0], p = 0.001), and migraine without anxiety or depression (1.0 [0.3-3.0], p < 0.001). The migraine with anxiety alone (7.0 [6.0-8.0], p = 0.011) group and migraine with anxiety and depression (7.0 [5.0-9.0], p = 0.018) group showed higher Visual Analogue Scale scores for pain intensity compare to migraine without anxiety or depression (6.0 [5.0-7.0]) group. Approximately 1/3 of migraineurs with anxiety had depression and 2/3 of migraineurs with depression had anxiety. Combination of anxiety and depression was associated with an increased headache frequency. Anxiety was associated with exacerbation of headache intensity.


Symptoms of gastroparesis: use of the gastroparesis cardinal symptom index in symptomatic patients referred for gastric emptying scintigraphy.
The Gastroparesis Cardinal Symptom Index (GCSI) was developed to assess symptoms of gastroparesis. The aim of this study was to correlate symptoms using the GCSI with delayed gastric emptying (DGE) in symptomatic patients referred for gastric emptying scintigraphy (GES). A total of 226 consecutive symptomatic patients referred for GES completed the 9-question GCSI. GES was performed using a (99)Tc-labeled egg meal. Gastroparesis was defined as DGE at 2 h and/or 4 h. Using linear regression, nausea (p = 0.09), not able to finish a normal-size meal (p = 0.005), postprandial fullness subscore (p = 0.01), and total GCSI score (p = 0.06) were predictors of the gastric retention values at 2 h, but not at 4 h. Patients with gastroparesis had significant higher symptom scores for nausea (p = 0.035) and vomiting (p = 0.040) compared to patients with normal gastric emptying. The positive predictive value varied between 51 and 61% for total GCSI scores between 20 and 35, respectively. The individual symptoms of nausea, vomiting, and early satiety were associated with DGE at 2 h but not at 4 h. In contrast, the total or average GCSI score did not reliably predict the diagnosis of gastroparesis in symptomatic patients referred for GES.


Cloning, expression and identification of a new trehalose synthase gene from Thermobifida fusca genome.
A new open reading frame in Thermobifida fusca sequenced genome was identified to encode a new trehalose synthase, annotated as "glycosidase" in the GenBank database, by bioinformatics searching and experimental validation. The gene had a length of 1830 bp with about 65% GC content and encoded for a new trehalose synthase with 610 amino acids and deduced molecular weight of 66 kD. The high GC content seemed not to affect its good expression in E. coli BL21 in which the target protein could account for as high as 15% of the total cell proteins. The recombinant enzyme showed its optimal activities at 25 degrees and pH 6.5 when it converted substrate maltose into trehalose. However it would divert a high proportion of its substrate into glucose when the temperature was increased to 37 degrees, or when the enzyme concentration was high Its activity was not inhibited by 5 mM heavy metals such as Cu2+, Mn2+, and Zn2+ but affected by high concentration of glucose. Blasting against the database indicated that amino acid sequence of this protein had maximal 69% homology with the known trehalose synthases, and two highly conserved segments of the protein sequence were identified and their possible linkage with functions was discussed.


Genotype-phenotype correlation in ocular von Hippel-Lindau (VHL) disease: the effect of missense mutation position on ocular VHL phenotype.
von Hippel-Lindau (VHL) disease is a dominantly inherited, multisystemic tumor syndrome caused by mutations in the VHL gene. This study was conducted to establish genotype-phenotype correlations between the positions of disease-causing missense mutations and the ocular phenotypes of VHL disease. Participants with clinically defined VHL disease and documented germline missense mutations in the VHL gene were identified in a cross-sectional study (n=412). Statistical analysis was used to correlate the position of the missense mutation in either the alpha- or beta-domain of the VHL protein with the ocular disease phenotype. Missense mutations among study participants were located in 47 of the 213 possible codons in the VHL gene. Almost all mutations (98.5%) were located in one of two structural domains of the VHL protein: the alpha- and beta-domains. alpha-Domain mutations were significantly associated with a higher prevalence of retinal capillary hemangioblastomas (RCHs) compared with the beta-domain mutations (P=0.016). Among patients with RCHs, the prevalence of the lesions in the juxtapapillary position was also significantly higher in patients with alpha-domain mutations (P=0.0017). Conversely, beta-domain mutations correlated with a higher prevalence of peripherally located RCHs (P=0.0104). The location of missense mutations in the VHL gene correlates significantly with the prevalence and phenotype of ocular disease, and as such, influences the risk of visual loss in affected patients. These genotype-phenotype correlations can assist in the prognostic counseling and follow-up of VHL patients and may provide a basis for molecular inferences on ocular VHL disease pathogenesis.


Cellulose modulates biofilm formation by counteracting curli-mediated colonization of solid surfaces in Escherichia coli.
In enterobacteria, the CsgD protein activates production of two extracellular structures: thin aggregative fimbriae (curli) and cellulose. While curli fibres promote biofilm formation and cell aggregation, the evidence for a direct role of cellulose as an additional determinant for biofilm formation is not as straightforward. The MG1655 laboratory strain of Escherichia coli only produces limited amounts of curli and cellulose; however, ectopic csgD expression results in strong stimulation of curli and cellulose production. We show that, in a csgD-overexpressing derivative of MG1655, cellulose production negatively affects curli-mediated surface adhesion and cell aggregation, thus acting as a negative determinant for biofilm formation. Consistent with this observation, deletion of the bcsA gene, necessary for cellulose production, resulted in a significant increase in curli-dependent adhesion. We found that cellulose production increased tolerance to desiccation, suggesting that the function of cellulose might be related to resistance to environmental stresses rather than to biofilm formation. Production of the curli/cellulose network in enterobacteria typically takes place at low growth temperature (<32 degrees C), but not at 37 degrees C. We show that CsgD overexpression can overcome temperature-dependent control of the curli-encoding csgBA operon, but not of the cellulose-related adrA gene, suggesting very tight temperature control of cellulose production in E. coli MG1655.


Optic neuritis in the two northernmost counties of Norway. A study of incidence and the prospect of later development of multiple sclerosis.
A study of the incidence of uncomplicated optic neuritis (ON) in the period 1972-1984 and the subsequent risk of later developing of multiple sclerosis (MS) was performed in the two northernmost counties of Norway. The incidence of ON was stable during the period. Of the 36 ON patients available to follow-up, 42% later developed MS. Mean time from debut of ON to the next symptom of MS was 2.2 years, median 1 year. There was one ethnic Lapp among the ON patients. The number of Lapps in the area is estimated to be about 26,000.


The influence of individual and regional factors on association between leisure time physical activity and psychological complaints among adolescents in Europe.
The aim of this study was to examine the association between leisure time physical activity and psychological complaints among adolescents and to determine to what extent this association is mediated by individual and regional factors. Data from the 2005/06 Health Behaviour in School-aged children (HBSC) survey, composed of 106,319 respondents aged 11, 13 and 15 from 20 European countries was analysed. Multilevel modeling showed that individual factors (gender, age and family socioeconomic status) were significant mediators of the association between leisure time physical activity and psychological complaints. The mediating effect of individual factors differed in the magnitude of the association. Regional differences in this association were not found. The findings suggest that individual factors contribute in explaining the association between leisure time physical activity and psychological complaints among adolescents. Future research should examine country specific characteristics which may influence this association.


Inositol phosphate multikinase dependent transcriptional control.
Production of lipid-derived inositol phosphates including IP4 and IP5 is an evolutionarily conserved process essential for cellular adaptive responses that is dependent on both phospholipase C and the inositol phosphate multikinase Ipk2 (also known as Arg82 and IPMK). Studies of Ipk2, along with Arg82 prior to demonstrating its IP kinase activity, have provided an important link between control of gene expression and IP metabolism as both kinase dependent and independent functions are required for proper transcriptional complex function that enables cellular adaptation in response to extracellular queues such as nutrient availability. Here we define a promoter sequence cis-element, 5'-CCCTAAAAGG-3', that mediates both kinase-dependent and independent functions of Ipk2. Using a synthetic biological strategy, we show that proper gene expression in cells lacking Ipk2 may be restored through add-back of two components: IP4/IP5 production and overproduction of the MADS box DNA binding protein, Mcm1. Our results are consistent with a mechanism by which Ipk2 harbors a dual functionality that stabilizes transcription factor levels and enzymatically produces a small molecule code, which together coordinate control of biological processes and gene expression.


Role of iron in the pathogenicity of Vibrio damsela for fish and mammals.
The ability to obtain iron of 14 isolates of Vibrio damsela with different degrees of virulence for mice and turbot (Scophthalmus maximus) has been evaluated in artificial and natural iron-restricted environments. All strains were capable of utilizing haemoglobin (Hb) and ferric ammonium citrate (FAC) as the sole iron sources in vitro. However, only virulent V. damsela strains were able to resist the bacteriostatic and bactericidal effects of human and turbot sera, their growth being enhanced by the addition of Hb and FAC. The inhibitory effect of these sera on the growth of the non-pathogenic strain (ATCC 35083), however, was reversed by heat treatment (56 degrees C for 60 min). The role of iron-availability on the virulence was investigated in iron-overloaded animals. The iron-treatment before the infection resulted in a significant reduction in the LD50 of virulent strains. This fact demonstrates a positive correlation between iron availability in host fluids and degree of virulence in the species Vibrio damsela.


Dental management of children with cancer.
Dental management of pediatric oncology patients is an important component of comprehensive supportive care. Oral complications associated with tumor directed treatment may be a direct result of the stomatotoxic effects of cancer therapy or the indirect effects of myelosuppression. These complications may be immediate or long-term. Appropriate dental supportive care has been shown to minimize the morbidity and potential mortality associated with these complications.


Chromatin modification mapping in nanochannels.
We report the simultaneous mapping of multiple histone tail modifications on chromatin that has been confined to nanofluidic channels. In these channels, chromatin is elongated, and histone modification can be detected using fluorescently tagged monoclonal antibodies. Using reconstituted chromatin with three distinct histone sources and two histone tail modification probes (H3K4me3 and H3K9ac), we were able to distinguish chromatin from the different sources. Determined ratios of the two modifications were consistent with the bulk composition of histone mixtures. We determined that the major difficulty in transitioning the mapping method to site-specific profiling within single genomic molecules is the interference of naturally aggregating, off-the shelf antibodies with the internal structure of chromatin.


Quantification of PCR amplification products of Brugia HhaI repeat DNA using a semiautomated Q-PCR system.
The sensitive, rapid and species-specific diagnosis of Brugia infections in humans or animal models is important in determining the level of parasitemia and the efficacy of chemotherapy or vaccinations. The HhaI family of highly repeated DNA sequences from Brugia have been useful in polymerase chain reaction (PCR)-based diagnosis of brugian filarial infections in blood samples and in mosquitoes. A PCR assay was developed using a biotinylated primer, a non-biotinylated primer and a species-specific chemiluminescent probe [tris[2,2'bipyridine] ruthenium (II) chelate, TBR] to detect PCR amplified Hhal family repeats. Individual blood samples from jirds infected with Brugia malayi or B. pahangi and with different levels of microfilaremia were tested in this assay. Known concentrations of Brugia DNA and DNA from the blood of uninfected control jirds were used as positive and negative controls, respectively. The PCR products generated by this method were analyzed using a semi-automated quantitative (Q)-PCR system. The levels of parasite DNA can be calculated from the luminosity units generated. Significant amounts of parasite DNA were detected in blood samples from infected jirds, and these values were correlated with the levels of microfilaremia. In contrast, reductions in circulating microfilaria following treatment with ivermectin correlated with low levels of measurable DNA. Using this system, we were also able to detect HhaI repeat DNA in the spleens of B. pahangi- infected jirds at 56 days post-infection when circulating microfilariae were not readily detectable. The results indicate that the species-specific Hhal Q-PCR detection and quantification method is rapid and sensitive, is useful in the detection of Brugia DNA in blood and other tissues and is suited for use in clinical settings because it does not require radioactive isotopes and gel-based protocols.


First-trimester sonographic diagnosis of holoprosencephaly: value of the "butterfly" sign.
To study the value of choroid plexus dysmorphology as a screening tool for the first-trimester sonographic diagnosis of holoprosencephaly in a high-risk population. A total of 378 consecutive pregnancies undergoing chorionic villus sampling between 11 and 14 weeks' gestation were scanned before the procedure, following the recommendations of the Fetal Medicine Foundation (London, England). A cross-sectional view of the fetal brain, including the visualization of both choroid plexuses (the "butterfly" sign), was obtained in all cases. There were 3 cases in which the butterfly sign was not identified. In these cases, the first-trimester diagnosis of holoprosencephaly was confirmed by the presence of a single monoventricular cavity and fused thalami. Two of these fetuses had features of facial dysmorphism at the time of presentation and 2 had extracranial anomalies, including a cystic hygroma in 1 and a small omphalocele and polydactyly in another. Chromosomal analysis showed trisomy 13 in 2 cases and a ring chromosome 13 in the other. This series suggests that failure to identify the butterfly sign is a warning sign of holoprosencephaly in the first trimester. Systematic identification of the butterfly sign at the time of sonographic assessment of nuchal translucency provides a valuable tool for the early screening of holoprosencephaly.


Conjugated linoleic acids.
Conjugated linoleic acid (CLA) has been studied extensively in both animal and human models. CLA supplementation has been attributed to provide several health benefits that are based largely upon animal and in vitro studies. Recent literature suggests that CLA supplementation possesses an anti-adipogenic role. However, the results of studies in humans have not been as consistent in this regard as anticipated from animal models. In addition to body composition, CLA also recently has been investigated in terms of exercise performance. The following review summarizes the most recent scientific investigations relative to CLA supplementation and its effects upon body composition and exercise performance. Additionally, recent investigations into the safety of CLA supplementation also are reviewed.


Reproductive technologies in developing countries.
Are there any ethical concerns about reproductive technologies that are specific or unique to developing countries? Three ethical concerns often mentioned specifically in regard to developing countries are (1), the "overpopulation argument"; (2) the limited resources argument; and (3) the ethical problem of poorly trained practitioners offering their services to unsuspecting and uninformed infertile individuals or couples. Each argument is explored in some detail, with the conclusion that ethical problems do, in fact, exist but are not unique to developing countries. Nevertheless, the difficulties relating to reproductive technologies are likely to be greater in developing countries than in developed ones because of limited resources and a larger number of poor people residing there.


MicroRNA-451 as a prognostic marker for diagnosis and lymph node metastasis of papillary thyroid carcinoma.
To investigate the diagnostic potentials of microRNA-451(miR-451) in papillary thyroid carcinoma (PTC) diagnosis and lymph node (LN) metastasis, formalin-fixed, paraffin-embedded (FFPE) tissue specimens corresponding to PTC tumors (n= 60) and their normal counterparts (Normal tissues Adjacent to Tumor, NAT, n= 60), along with sera from PTC patients with malignant tumors (n= 70) and benign lesions (n= 70) were analyzed for the expression of miR-451 by real-time PCR. The usefulness of miR-451 expression as a prognostic marker for diagnosis of PTC malignancies was evaluated by Receiver Operating Curve (ROC). We reported that when compared to those in NAT, the levels of miR-451 in FFPE tissues from various stages of PTC patients (n= 60) were significantly lower (Mean ± SEM; 12.62 ± 1.73 vs 38.8 ± 3.51, p< 0.0001). Receiver operating curve (ROC) analysis revealed that the area under curve (AUC) was 0.808; suggesting miR-451 expression was a reliable tissue biomarker for PTC malignancies. Further in depth analyses of these specimens revealed that miR-451 levels were significantly lower in PTC patients with lymph node (LN) metastasis than those without LN metastasis (3.96 ± 1.67 vs. 14.15 ± 1.95, p= 0.006) with calculated AUC of 0.792, supporting the notion that miR-451 expression was also a good indicator for PTC lymph node involvements. Analyses sera from the cohorts of PTC patients indicated that miR-451 levels in patients with malignant lesions (n= 70) were significantly lower (10.72 ± 1.52 vs. 19.28 ± 2.73, p= 0.010) than those with benign ones (n= 70). Parallel analyses of serum miR-451 levels in patients with LN metastasis also showed that they were significantly lower when compared to those without LN metastasis (6.79 ± 2.29 vs. 12.08 ± 1.86, p= 0.017). ROC analyses revealed that AUC was 0.626 for malignancies and was 0.690 for lymph node involvement, respectively, suggesting that miR-451was a modest blood based biomarker for PTC malignancies and lymph node metastasis. We concluded that miR-451 expression is a reliable FFPE tissue biomarker for PTC malignancies and it may have potentials to become a noninvasive, blood-based biomarker for PTC diagnosis and evaluation of LN status.


Epidemiology of group B streptococcal colonization in pregnancy.
These data support the conclusions that: 1) An intrapartum screening program for GBS colonization favorably affects the outcome of GBSD, with mortality decreased to 10%. 2) Four risk factors--ABO blood group B, unregistered status, PROM and premature labor at less than 32 weeks--identify 83% of mothers whose infants develop GBSD. 3) There is no association between internal monitoring and mode of delivery and the vertical transmission of GBS. 4) Duration of membrane rupture does not affect vertical transmission or development of early-onset disease. This differs from previous findings. 5) Lastly, our findings regarding the natural history of asymptomatic infant carriers suggest that these infants play a previously unsuspected role in the epidemiology of GBS in the entire population.


Homotypic and heterotypic exclusion of vesicular stomatitis virus replication by high levels of recombinant polymerase protein L.
The recombinant polymerase protein L of vesicular stomatitis virus (VSV) expressed in COS cells is able to transcribe and replicate the viral genome, resulting in complementation of temperature-sensitive polymerase mutants of VSV at the restrictive temperature (M. Schubert, G. G. Harmison, C. D. Richardson, and E. Meier, Proc. Natl. Acad. Sci. USA 82:7984-7988, 1985). Here we report that the efficiency of complementation is dependent on the level of L protein expression. Unexpectedly, only cells expressing low levels of recombinant L protein efficiently complemented tsL gene mutants, whereas cells with high levels of L protein did not. In fact, in all cells with high levels of L protein expression, which at 40 h posttransfection represented almost the total number of transfected cells, viral replication not only of the temperature-sensitive mutant but also of wild-type VSV was excluded. The inhibition of VSV appeared to occur at an early stage of the infectious cycle, and wild-type virus of the same serotype (Indiana) as the recombinant L protein as well as wild-type virus of a different serotype (New Jersey) was affected. Measles virus, on the other hand, was not arrested in cells with high levels of recombinant L protein, demonstrating that these cells were still capable of supporting a viral infection. The expression of high levels of only the amino-terminal half of the L protein from a recombinant mutant L gene that contains a small out-of-frame deletion in the middle of the L gene did not inhibit a VSV infection. Since the level of amplification for both L- and truncated L-encoding vectors is similar, we conclude that the arrest of VSV was caused by high levels of functional full-length L protein itself and not by high levels of vector-encoded L mRNA or other vector products or by side effects of vector amplification. These data strongly support the idea that the highly conserved gene order of nonsegmented negative-strand viruses and the sequential and attenuated mode of transcription are important regulatory elements which balance the intracellular concentration of viral proteins. They both assure that the L gene is the last and the least frequently transcribed gene, giving rise to low levels of L protein necessary for efficient replication.


Studies on metabolites and metabolic pathways of bulleyaconitine A in rat liver microsomes using LC-MS(n) combined with specific inhibitors.
Bulleyaconitine A (BLA) from Aconitum bulleyanum plants is usually used as anti-inflammatory drug in some Asian countries. It has a variety of bioactivities, and at the same time some toxicities. Since the bioactivities and toxicities of BLA are closely related to its metabolism, the metabolites and the metabolic pathways of BLA in rat liver microsomes were investigated by HPLC-MS(n). In this research, the 12 metabolites of BLA were identified according to the results of HPLC-MS(n) data and the relevant literature. The results showed that there are multiple metabolites of BLA in rat liver microsomes, including demethylation, deacetylation, dehydrogenation deacetylation and hydroxylation. The major metabolic pathways of BLA in rat liver microsomes were clarified by HPLC-MS combined with specific inhibitors of CYP450 isoforms. As a result, CYP3A and 2C were found to be the principal CYP isoforms contributing to the metabolism of BLA. Moreover, CYP2D6 and 2E1 are also more important CYP isoforms for the metabolism of BLA. While CYP1A2 only affected the formation rate of M11, its effect on the metabolism of BLA is very small.


[HERG K+ channel, the target of anti-arrhythmias drugs].
Rapidly activating component of delayed rectifier potassium current (I(Kr)) plays a key role in the repolarization phase of cardiac action potential. Human ether-a-go-go-related gene (HERG) encodes the alpha subunit of this potassium channel. Mutations of HERG gene induce genetic long QT syndrome (LQTS). Furthermore, I(Kr)/HERG is the target of some drugs which may cause cardiac QT interval prolongation. Some other drugs with different chemical structures also may block the channel and prolong QT interval, which even developed into acquired arrhythmias. This review summarized the recent progress of structure, gating mechanisms and functions of I(Kr)/HERG channel, I(Kr)/HERG related arrhythmias, interaction between K+ channel and drugs, and strategies of grading-up the I(Kr)/HERG target.


Levels and pattern of polybrominated diphenyl ethers in eggs of Antarctic seabirds: Endemic versus migratory species.
Chinstrap and gentoo penguins are endemic species that live year round south of the Antarctic Convergence. South polar skua is a migratory seabird that can be observed in Antarctica during the breeding season (i.e., austral summer). This study compares concentration and pattern of polybrominated diphenyl ethers (PBDEs) in eggs of seabirds breeding at King George Island, Antarctic Peninsula. PBDEs in south polar skua eggs are approximately 20 times higher than in penguin eggs suggesting that skuas are more exposed to contaminants during the non-breeding season when they migrate to waters of the northern hemisphere. The pattern of PBDE congeners also differs between south polar skua and penguin eggs. The latter exhibited a pattern similar to that found in the local biota. In contrast, the congener pattern in south polar skua eggs suggests that birds breeding at King George Island may winter in the northwestern Pacific Ocean.


Diversity of the Photosynthetic Paulinella Species, with the Description of Paulinella micropora sp. nov. and the Chromatophore Genome Sequence for strain KR01.
The thecate filose amoeba Paulinella chromatophora is a good model organism for understanding plastid organellogenesis because its chromatophore was newly derived from an alpha-cyanobacterium. Paulinella chromatophora was the only known photosynthetic Paulinella species until recent studies that suggested a species level of diversity. Here, we described a new photosynthetic species P. micropora sp. nov. based on morphological and molecular evidence from a newly established strain KR01. The chromatophore genome of P. micropora KR01 was fully determined; the genome was 976,991bp in length, the GC content was 39.9%, and 908 genes were annotated. A pairwise comparison of chromatophore genome sequences between strains KR01 and FK01, representing two different natural populations of P. micropora, showed a 99.85% similarity. Differences between the two strains included single nucleotide polymorphisms (SNPs) in CDSs, which resulted in 357 synonymous and 280 nonsynonymous changes, along with 245 SNPs in non-coding regions. Indels (37) and microinversions (14) were also detected. Species diversity for photosynthetic Paulinella was surveyed using samples collected from around the world. We compared our new species to two photosynthetic species, P. chromatophora and P. longichromatophora. Phylogenetic analyses using four gene markers revealed three distinct lineages of photosynthetic Paulinella species including P. micropora sp. nov.


Toll-like receptor 3 is critical for coxsackievirus B4-induced type 1 diabetes in female NOD mice.
Group B coxsackieviruses (CVBs) are involved in triggering some cases of type 1 diabetes mellitus (T1DM). However, the molecular mechanism(s) responsible for this remain elusive. Toll-like receptor 3 (TLR3), a receptor that recognizes viral double-stranded RNA, is hypothesized to play a role in virus-induced T1DM, although this hypothesis is yet to be substantiated. The objective of this study was to directly investigate the role of TLR3 in CVB-triggered T1DM in nonobese diabetic (NOD) mice, a mouse model of human T1DM that is widely used to study both spontaneous autoimmune and viral-induced T1DM. As such, we infected female wild-type (TLR3(+/+)) and TLR3 knockout (TLR3(-/-)) NOD mice with CVB4 and compared the incidence of diabetes in CVB4-infected mice with that of uninfected counterparts. We also evaluated the islets of uninfected and CVB4-infected wild-type and TLR3 knockout NOD mice by immunohistochemistry and insulitis scoring. TLR3 knockout mice were markedly protected from CVB4-induced diabetes compared with CVB4-infected wild-type mice. CVB4-induced T-lymphocyte-mediated insulitis was also significantly less severe in TLR3 knockout mice compared with wild-type mice. No differences in insulitis were observed between uninfected animals, either wild-type or TLR3 knockout mice. These data demonstrate for the first time that TLR3 is 1) critical for CVB4-induced T1DM, and 2) modulates CVB4-induced insulitis in genetically prone NOD mice.


Post-bariatric surgery reconstruction: patient myths, perceptions, cost, and attainability strategies.
A discrepancy exists between patient perceptions of post-bariatric surgery reconstruction and cost, value, and ultimate attainability. The authors investigated prospective gastric bypass patients to identify misconceptions and strategies to aid in the attainability of post-bariatric surgery reconstruction. One hundred seventy-six prospective gastric bypass patients were surveyed for perceptions of plastic surgery, a "club" concept integrating plastic surgical/bariatric teams, and payment strategies. Cost comparisons were set up for comparison with major consumer purchases. Outcome measures were assessed by univariate analyses. One hundred seventy-four patients (139 women and 35 men; mean age, 42.3 years; mean body mass index, 49.3) completed the survey; 65.9 percent expressed an interest in plastic surgery (women were more interested than men) (p < 0.05); 73.1 percent wanted their plastic surgeon affiliated with the bariatric surgeon/team; 47 percent wanted to meet the plastic surgeon before their gastric bypass; and 14.4 percent equated the cost of a total body lift to the cost of a new car versus 31.9 percent for a trip to Disneyworld, 23.8 percent for a television, and 16.3 percent for a radio. Estimated costs for plastic surgery were undervalued by 60 percent. Sixty percent were interested in a club with a monthly fee that would go toward future plastic surgery. Other payment strategies were less popular. None of the independent variables predicted the degree of interest in any particular plan. Future gastric bypass patients, particularly women, are a unique population with common misconceptions regarding post-bariatric surgery reconstruction. Early patient education and financial awareness, in combination with preexisting or newly created bariatric centers, may improve attainability for this population.


Amylase release from streptolysin O-permeabilized pancreatic acini.
Intracellular mediators of exocytosis were investigated using isolated mouse pancreatic acini permeabilized with the bacterial toxin streptolysin O (SLO). Permeabilization was demonstrated by fluorescent staining with ethidium bromide and fluorescein diacetate and release of cytoplasmic lactate dehydrogenase. When SLO-permeabilized acini were incubated at 37 degrees C in Ca2(+)-EGTA buffers containing MgATP, amylase secretion was Ca2+ dependent with an EC50 of 0.40 microM Ca2+ and a maximally effective Ca2+ concentration of 1 microM. Maximal amylase secretion was 330% of that in Ca2(+)-free buffer (basal). The nonhydrolyzable GTP analogue guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; 30 microM) increased the maximal secretion to 451% of basal in the presence of 1 microM Ca2+ and decreased the EC50 to 0.14 microM Ca2+. Removal of ATP plus addition of antimycin A and 2-deoxy-D-glucose inhibited Ca2(+)-dependent, GTP gamma S-enhanced amylase secretion by 56%. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA; 1 microM) also enhanced maximal secretion to 450% of basal and decreased the EC50 to 0.18 microM Ca2+. Enhancement of amylase secretion by submaximal concentrations of GTP gamma S or TPA was inhibited by the protein kinase C inhibitor staurosporine. These results suggest that Ca2+ stimulation of amylase secretion is potentiated by activation of protein kinase C. However, the enhancement of secretion by GTP gamma S and TPA was additive at their maximally effective concentrations, suggesting that another G protein(s) maybe involved in the terminal steps of exocytosis.


Using Adaptive Computer-based Instruction to Teach Staff to Implement a Social Skills Intervention.
This study evaluated the effectiveness of an adaptive, computer-based staff training software program called Train-to-Code (TTC) to teach the administration of a social skills intervention. The software program actively trained participants to identify whether video models illustrated each step of the procedure effectively or ineffectively. Multiple exemplars of each step of the social skills task analysis were represented. Most-to-least prompting as well as feedback and error correction were embedded into the software program and prompts were faded through seven levels as the participant reached criterion accuracy. A multiple-probe across participants design was used to evaluate the effectiveness of this program by comparing pre- and post-training in vivo probes conducted with a confederate learner. All participant scores increased from pre-training to post-training, indicating that Train-to-Code was effective at teaching administration of the social skills intervention. These results have implications for training staff in applied community settings. Due to Train-to-Code's ability to be internet-based and to measure actual viewing performance, it has the potential for "distance training" deliveries.


Informal caregivers of patients with disorders of consciousness: experience of ambiguous loss.
This study aimed at better understanding of the complex psychological process underlying the demanding situation of taking care of a relative with disorder of consciousness (DOCs). This is a qualitative study based on the grounded theory constant comparative method. Narratives of informal caregivers were collected through in-depth interviews with a psychologist. A three-step coding scheme was applied: coding of narratives to label the specific contents; organization of codes into sub-categories and categories; and theoretical coding to describe the relation between categories. Twenty informal caregivers participated in one in-depth interview between December 2011 and May 2012. Four major themes emerged: Another person with past in common; Losing and finding myself; Old and new ways of being in relationship; and Dealing with concerns. These themes represent caregivers' efforts to deal with the situation in which their relative is at the same time present and absent. The core salient feature emerging from all these themes is the experience of ambiguous loss. Features of ambiguous loss that emerged in this study could guide clinicians' interventions to support adjustment of caregivers of patients with DOCs.


Ex vivo analysis of thymic CD4 T cells in nonobese diabetic mice with tetramers generated from I-A(g7)/class II-associated invariant chain peptide precursors.
The MHC determines susceptibility and resistance to type 1 diabetes in humans and nonobese diabetic (NOD) mice. To investigate how a disease-associated MHC molecule shapes the T cell repertoire in NOD mice, we generated a series of tetramers from I-A(g7)/class II-associated invariant chain peptide precursors by peptide exchange. No CD4 T cell populations could be identified for two glutamic acid decarboxylase 65 peptides, but tetramers with a peptide mimetic recognized by the BDC-2.5 and other islet-specific T cell clones labeled a distinct population in the thymus of young NOD mice. Tetramer-positive cells were identified in the immature CD4(+)CD8(low) population that arises during positive selection, and in larger numbers in the more mature CD4(+)CD8(-) population. Tetramer labeling was specific based on the use of multiple control tetramers, including one with a single amino acid analog peptide in which a critical TCR contact residue was substituted. The T cell population was already present in the thymus of 2-wk-old NOD mice before the typical onset of insulitis and was detected in B10 mice congenic for the NOD MHC locus, but not B10 control mice. These results demonstrate that a T cell population can expand in the thymus of NOD mice to levels that are at least two to three orders of magnitude higher than estimated for a given specificity in the naive T cell pool. Based on these data, we propose a model in which I-A(g7) confers susceptibility to type 1 diabetes by biasing positive selection in the thymus and later presenting peptides from islet autoantigens to such T cells in the periphery.


Bioactive diterpenoid containing a reversible "spring-loaded" (E,Z)-dieneone Michael acceptor.
Three new briarane diterpenoids, briareolate esters L-N (1-3), have been isolated from a gorgonian Briareum asbestinum. Briareolate esters L (1) and M (2) are the first natural products possessing a 10-membered macrocyclic ring with a (E,Z)-dieneone and exhibit growth inhibition activity against both human embryonic stem cells (BG02) and a pancreatic cancer cell line (BxPC-3). Briareolate ester L (1) was found to contain a "spring-loaded" (E,Z)-dieneone Michael acceptor group that can form a reversible covalent bond to model sulfur-based nucleophiles.


Transcriptomic Analysis of Ovaries from Pigs with High And Low Litter Size.
Litter size is one of the most important economic traits for pig production as it is directly related to the production efficiency. Litter size is affected by interactions between multiple genes and the environment. While recent studies have identified some genes associated with prolificacy in pigs, transcriptomic studies of specific genes affecting litter size in porcine ovaries are rare. In order to identify candidate genes associated with litter size in swine, we assessed gene expression differences between the ovaries of Yorkshire pigs with extremely high and low litter sizes using the RNA-Seq method. A total of 1 243 differentially expressed genes were identified: 897 genes were upregulated and 346 genes were downregulated in high litter size ovary samples compared with low litter size ovary samples. A large number of these genes related to steroid hormone regulation in animal ovaries, including 59 Gene Ontology terms and 27 Kyoto Encyclopedia of Genes and Genomes pathways involved in steroid biosynthesis and ovarian steroidogenesis. From these differentially expressed genes, we identified a total of 11 genes using a bioinformatics screen that may be associated with high litter size in Yorkshire pigs. These results provide a list of new candidate genes for porcine litter size and prolificacy to be further investigated.


Endoscopic extraction of foreign bodies from the duodenum: four cases in infancy.
Four cases of foreign bodies in the duodenum were treated using a flexible fibre-optic panendoscope. All the patients were boys and eight months to four years of age. The ingested foreign materials were an injection needle, a marking pin, a hairpin and a curtain hook. Endoscopic extraction was attempted, because the ingested objects might cause perforation or obstruction of the gastrointestinal tract. Until recently, they had to be carefully watched or prophylactic operation suggested. Under general anaesthesia, duodenal endoscopy was easily performed and extraction of foreign bodies was not found to be difficult during infancy. This is considered to be a safer and less hazardous way than careful watching or prophylactic operation.


Bioactive constituents of oleanane-type triterpene saponins from the roots of Glycyrrhiza glabra.
Three new oleanane-type triterpene saponins, namely licorice-saponin M3 (1), licorice-saponin N4 (2), and licorice-saponin O4 (3), an artificial product (4), as well as five known triterpene glucuronides (5-9), were isolated from the roots of Glycyrrhiza glabra L. Their structures were established using 1D and 2D NMR spectroscopy, mass spectrometry, and by comparison with spectroscopic data reported in the literature. The inhibitory effects of the selected compounds on neuraminidase were evaluated, and the preliminary structure-activity relationship was also predicted.


[Effect of exogamy on morbidity among children during the first three years of life].
The incidence of common diseases among children in the first three years of life was studied in relation to the degree of outcrossing in family history, the level of education of both parents, and the age of entering nursery school. A total of 526 children (274 boys and 252 girls) were inspected. The factors under study proved to have no effect on morbidity among children under one year of age. However, morbidity during the second and third years of life depended on the degree of outcrossing in the children's family background, the educational level of their mothers, and the age of their entrance into nursery school. Higher morbidity at this age was characteristic of children born of parents belonging to different ethnic groups, and this situation was independent of social factors. The role of genetic coadaptation and epistasis in determining the relationship between outcrossing and morbidity is discussed.


Detection of Prochlorothrix in brackish waters by specific amplification of pcb genes.
Prochlorothrix hollandica is the only filamentous chlorophyll b (Chlb)-containing oxyphotobacterium that has been found in freshwater habitats to date. Chlb serves as a light-harvesting pigment which is bound to special binding proteins (Pcb). Even though Prochlorothrix was initially characterized as a highly salt-sensitive species, we detected it in a brackish water environment that is characterized by salinities of up to 12 practical salinity units. Using PCR and reverse transcription, we amplified pcb gene fragments of phytoplankton samples taken along a salinity gradient in the eutrophic Darss-Zingst estuary (southern Baltic Sea). After sequencing, high levels of homology to the pcbB and pcbC genes of P. hollandica were found. Furthermore, autofluorescence of Prochlorothrix-like filaments that indicated that Chlb was present was detected in enrichment cultures prepared from the estuarine phytoplankton. The detection of Chlb-containing filaments, as well as the pcb and 16S ribosomal DNA sequences, suggests that Prochlorothrix is an indigenous genus in the Darss-Zingst estuary and may also inhabit many other brackish water environments. The potential of using pcb gene detection to differentiate Prochlorothrix from morphologically indistinguishable species belonging to the genera Pseudanabaena and Planktothrix (Oscillatoria) in phytoplankton analyses is discussed.


Effect of Rosuvastatin on Bovine Pericardial Aortic Tissue Valve Calcification in a Rat Subdermal Implantation Model.
There are pathophysiologic similarities between calcification and atherosclerosis because both are the product of an active inflammatory process. The aim of this study was to examine the effects of statin treatment on calcification in bovine pericardial tissue valves. Forty Sprague-Dawley rats were randomly divided into 4 groups according to hypercholesterolemia induction and statin intake (Group 1, n=10: normal diet without statin treatment, Group 2, n=10: normal diet with statin treatment, Group 3, n=10: high fat diet without statin treatment, Group 4, n=10: high fat diet with statin treatment). Serum lipid levels were measured just before the experiment and after 4 and 12 weeks. Bovine pericardial tissue valve cusps were surgically implanted in rat dorsal subcutis at 4 weeks. After the surgery, statin was administered daily to Groups 2 and 4. Serum interleukin-6 (IL-6) level was measured at 5 weeks. Cusps were explanted at 12 weeks and calcium levels were determined by atomic absorption spectroscopy. Mean IL-6 was significantly higher in Group 3 at 5 weeks (7.14, 2.03, 31.70, and 6.90 pg/dL for each group, respectively). Mean calcium level in Group 3 was significantly higher among groups but Group 4 was significantly lower compared to Group 3 and was similar to Group 1, 2 (1.86, 1.92, 2.55, and 1.80 mg/g for each group, respectively, p<0.01). Hypercholesterolemia may be a significant risk factor for bovine pericardial valve calcification. Statin treatment significantly attenuated calcification of bovine pericardial valve tissue in a rat subdermal implantation model and might prolong the durability of bioprostheses.


[Synthesis and properties of bromocriptine (author's transl)].
The bromination of alpha-ergokryptine, a genuine ergot alkaloid of the peptide type, in position 2 of the indol nucleus to 2-bromo-alpha-ergokryptine is described. Its transformation to the methanesulfonate led to the prolactin inhibitor bromocriptine-methanesulfonate, Parlodel.


Proton Versus Intensity-Modulated Radiation Therapy: First Dosimetric Comparison for Total Scalp Irradiation.
Total scalp irradiation (TSI) is used to treat malignancies of the scalp and face, including angiosarcomas, nonmelanoma skin cancers, and cutaneous lymphomas. Owing to the irregularity of the scalp contour and the presence of underlying critical organs at risk (OARs), radiation planning is challenging and technically difficult. To address these complexities, several different radiation therapy techniques have been used. These include the combined lateral photon-electron technique (3DRT), intensity-modulated radiation therapy (IMRT)/volumetric arc therapy (VMAT), helical tomotherapy (HT), and mold-based high-dose-rate brachytherapy (HDR BT). However, the use of proton radiation therapy (PRT) has never been documented. A 71-year-old, immunosuppressed man presented with recurrent nonmelanoma skin cancer of the scalp. He was successfully treated at our center with PRT to deliver TSI. A comparative VMAT treatment plan was generated and dose to critical OARs was compared. We present the first clinical case report of PRT for TSI and dosimetric comparison to a VMAT plan. The PRT and VMAT plans provided equivalent target volume coverage; however, the PRT plan significantly reduced dose to the brain, hippocampi, and optical apparatus. TSI planned with PRT is relatively straightforward from a planning perspective and does not require a bolus. It also has the potential to decrease radiation therapy-related toxicity. However, PRT is relatively expensive and not universally available. The uncertainty surrounding the end-range of the proton beam is a consideration. Although there are potential disadvantages to using PRT for TSI, its use should be considered by treating radiation oncologists and referring physicians.


Sex comparison of hamstring structural and material properties.
Musculotendinous stiffness provides an estimate of resistance to joint perturbation, thus contributing to joint stability. Females demonstrate lesser hamstring stiffness than males, potentially contributing to the sex discrepancy in anterior cruciate ligament injury risk. However, it is unclear if the sex difference in hamstring stiffness is due to differences in muscle size or to inherent/material properties of the musculotendinous unit. It was hypothesized that hamstring stiffness, stress, strain, and elastic modulus would be greater in males than in females, and that hamstring stiffness would be positively correlated with muscle size. Stiffness was assessed in 20 males and 20 females from the damping effect imposed by the hamstrings on oscillatory knee flexion/extension following joint perturbation. Hamstring length and change in length were estimated via motion capture, and hamstring cross-sectional area was estimated using ultrasound imaging. These characteristics were used to calculate hamstring material properties (i.e., stress, strain, and elastic modulus). Stiffness was significantly greater in males than in females (P<0.001). However, stress, strain, and elastic modulus did not differ across sex (P>0.05). Stiffness was significantly correlated with cross-sectional area (r=0.395, P=0.039) and the linear combination of cross-sectional area and resting length (R(2)=0.156, P=0.043). Male's hamstrings possess a greater capacity for resisting changes in length imposed via joint perturbation from a structural perspective, but this property is similar across sex from a material perspective. Females demonstrate lesser hamstring stiffness compared to males in response to standardized loading conditions, indicating a compromised ability to resist changes in length associated with joint perturbation, and potentially contributing to the higher female ACL injury risk. However, the difference in hamstring stiffness is attributable in large part to differences in muscle size.


Bioassay guided fractionation and identification of active anti-inflammatory constituent from Delonix elata flowers using RAW 264.7 cells.
Delonix elata (L.) Gamble (Fabaceae) has been used in the Indian traditional medicine system to treat rheumatism and inflammation. To assess the anti-inflammatory effect of Delonix elata flowers and to isolate the active principle. The prompt anti-inflammatory constituent was isolated from Delonix elata flower extracts using bioassay guided fractionation in liposaccharide (LPS) stimulated RAW 264.7 macrophage cell line. The anti-inflammatory activity of extracts/fractions/sub-fractions/compounds (10, 25, and 50 µg/ml) was evaluated by estimating the levels of nitric oxide (NO), TNF-α, and IL-1β after 24 h of LPS induction (1 μg/ml). The isolated active compound was subjected to NMR, IR, and UV analyses for structure determination. In an attempt to search for anti-inflammatory constituents, the active pure principle was isolated and crystallized as a white compound from Delonix elata flowers methanol extract. This active compound (50 µg/ml) decreased the release of inflammatory mediators levels such as NO (0.263 ± 0.03 µM), TNFα (160.20 ± 17.57 pg/ml), and IL-1β (285.79 ± 15.16 pg/ml) significantly (p < 0.05); when compared to the levels of NO (0.774 ± 0.08 µM), TNFα (501.71 ± 25.14 pg/ml), and IL-1β (712.68 ± 52.25 pg/ml) from LPS-stimulated macrophage cells. The active compound was confirmed as hesperidin with NMR, IR, and UV spectroscopy data. This is the first report of this compound from Delonix elata flowers. The findings of the study support the traditional use of Delonix elata flowers to treat inflammation.


A Tale of Two Counties: Natives' Opinions Toward Immigration in North Carolina.
This paper compares native residents' opinions and perceptions regarding immigration using a representative survey from a pair of matched North Carolina counties-one that experienced recent growth of its foreign-born population and one that did not. Drawing from several theoretical perspectives, including group threat, contact theory, and symbolic politics, we formulate and empirically evaluate several hypotheses. Results provide limited evidence that competition and threat influence formation of opinions about immigration, with modest support for claims that parents with school-aged children harbor more negative views of immigration than their childless counterparts. Except for residents in precarious economic situations, these negative opinions appear unrelated to the immigrant composition of the community. Claims that the media promotes negative views of immigration receive limited support, but this relationship is unrelated to the volume of local immigration. Finally, sustained contacts with foreign-born residents outside work environments are associated with positive views of immigration, but superficial contacts appear to be conducive to anti-immigration sentiments. Political orientation, educational attainment and indicators of respondents' tolerance for diversity explain most of the difference between the two counties in overall support for immigration.


Estimating the rate constant of cyclic GMP hydrolysis by activated phosphodiesterase in photoreceptors.
The early steps of light response occur in the outer segment of rod and cone photoreceptor. They involve the hydrolysis of cGMP, a soluble cyclic nucleotide, that gates ionic channels located in the outer segment membrane. We shall study here the rate by which cGMP is hydrolyzed by activated phosphodiesterase (PDE). This process has been characterized experimentally by two different rate constants beta(d) and beta(sub): beta(d) accounts for the effect of all spontaneously active PDE in the outer segment, and beta(sub) characterizes cGMP hydrolysis induced by a single light-activated PDE. So far, no attempt has been made to derive the experimental values of beta(d) and beta(sub) from a theoretical model, which is the goal of this work. Using a model of diffusion in the confined rod geometry, we derive analytical expressions for beta(d) and beta(sub) by calculating the flux of cGMP molecules to an activated PDE site. We obtain the dependency of these rate constants as a function of the outer segment geometry, the PDE activation and deactivation rates and the aqueous cGMP diffusion constant. Our formulas show good agreement with experimental measurements. Finally, we use our derivation to model the time course of the cGMP concentration in a transversally well-stirred outer segment.


The cellular ceramide transport protein CERT promotes Chlamydia psittaci infection and controls bacterial sphingolipid uptake.
Chlamydiaceae are bacterial pathogens that cause diverse diseases in humans and animals. Despite their broad host and tissue tropism, all Chlamydia species share an obligate intracellular cycle of development and have evolved sophisticated mechanisms to interact with their eukaryotic host cells. Here, we have analysed interactions of the zoonotic pathogen Chlamydia psittaci with a human epithelial cell line. We found that C. psittaci recruits the ceramide transport protein (CERT) to its inclusion. Chemical inhibition and CRISPR/Cas9-mediated knockout of CERT showed that CERT is a crucial factor for C. psittaci infections thereby affecting different stages of the infection including inclusion growth and infectious progeny formation. Interestingly, the uptake of fluorescently labelled sphingolipids in bacteria inside the inclusion was accelerated in CERT-knockout cells indicating that C. psittaci can exploit CERT-independent sphingolipid uptake pathways. Moreover, the CERT-specific inhibitor HPA-12 strongly diminished sphingolipid transport to inclusions of infected CERT-knockout cells, suggesting that other HPA-12-sensitive factors are involved in sphingolipid trafficking to C. psittaci. Further analysis is required to decipher these interactions and to understand their contributions to bacterial development, host range, tissue tropism, and disease outcome.


Close - but not distant - conditioned flanker emotion affects crowding.
Crowding is affected by conditioned stimulus emotion. This effect is clearly observed for conditioned flankers, but only marginally pronounced for conditioned targets. Studies on the processing of emotional stimuli suggest that the magnitude of the emotional effect depends on the presentation depth in that effects of emotion increase with decreasing distance to the observer in depth. Based on respective findings, we investigate crowding with stimuli of conditioned negative and neutral emotion across real depth; that is, stimuli were either presented closer, at or farther away than the fixation depth. Conditioned emotion of flankers affected crowding when flankers were presented closer than or at fixation depth, which is also the distance the target was presented at. Farther away than the fixation depth, flanker emotion did not alter crowding (Experiment 1a). Conditioned target emotion, however, did only show weak effects on crowding; neither when flankers (Experiment 1b) nor when targets were varied in depth (Experiment 2) there was a clear effect of target emotion, replicating findings in two-dimensional settings. Taken together, the results suggest that flanker's emotional associations can become important for crowding, although, it depends on the special processing characteristics of stimulus emotion in depth. The conditioned emotion of targets scarcely affected crowding.


Inhibition of intracranial hemangioma growth and hemorrhage by TNFSF15.
Hemangioblastoma (HB) is an abnormal intracranial buildup of blood vessels that exhibit a great potential for hemorrhage. Surgical options are limited, and few medications are available for treatment. We show here by immunohistochemical analysis that HB lesions display highly increased levels of VEGF expression and macrophage/microglia infiltration compared with those in normal brain tissues. In the meantime, TNF superfamily 15 (TNFSF15) (also known as vascular endothelial growth inhibitor), an antiangiogenic cytokine, is highly expressed in normal brain blood vessels but diminished in HB lesions. We set up a brain hemangioma model by using mouse bEnd.3 cells of a T antigen-transformed endothelial cell line that produce a large amount of VEGF. When implanted in mouse brains, these cells form lesions that closely resemble the pathologic characteristics of HB. Retroviral infection of bEnd.3 cells with TNFSF15 leads to inhibition of VEGF production and retardation of hemangioma formation. Similar results are obtained when wild-type bEnd.3 cells are implanted in the brains of transgenic mice overexpressing TNFSF15. Additionally, TNFSF15 treatment results in enhanced pericyte coverage of the blood vessels in the lesions together with reduced inflammatory cell infiltration and decreased hemorrhage. These findings indicate that the ability of TNFSF15 to counterbalance the abnormally highly angiogenic and inflammatory potential of the microenvironment of HB is of therapeutic value for the treatment of this disease.-Yang, G.-L., Han, Z., Xiong, J., Wang, S., Wei, H., Qin, T.-T., Xiao, H., Liu, Y., Xu, L.-X., Qi, J.-W., Zhang, Z.-S., Jiang, R., Zhang, J., Li, L.-Y. Inhibition of intracranial hemangioma growth and hemorrhage by TNFSF15.


Recovery in vivo and in vitro of alpha-adrenoceptor responses and radioligand binding after phenoxybenzamine.
Phenoxybenzamine is an irreversible, selective alpha 1-adrenoceptor antagonist that results in long-lasting attenuation of the effects of alpha-adrenoceptor agonists in vivo and in vitro. We have studied in rabbits the time course of recovery of in vivo pressor responses to phenylephrine and in vitro contractile responses of spiral strips of renal artery to phenylephrine and noradrenaline. The maximum number of binding sites and the dissociation constant has been determined using 3H-prazosin in spleen and heart membranes prepared at intervals up to 8 days after phenoxybenzamine 5 mg/kg intravenously. In vitro contractile responses recovered over 2-3 days and by 4 days the EC50 was lower than control. In vivo pressor responses recovered over 5-8 days to control levels. The number of binding sites was only 50% of control at 8 days. It is proposed that under the conditions studied the recovery of binding sites may provide an index of turnover of alpha-adrenoceptors. The results also suggest that postreceptor mechanisms contribute to the increased responses observed in vitro.


The Mediating Effect of Depression on the Relation Between Interpersonal Needs and Suicidal Ideation Among Chinese Transgender Women.
Transgender women are at high risk of depression and suicidal ideation. The interpersonal theory of suicide proposes that suicidal ideation could be a consequence of high interpersonal needs (thwarted belongingness and perceived burdensomeness). The current study tests this theory and investigates whether depression could mediate the relationship between interpersonal needs and suicidal ideation among transgender women in Shenyang, China. A total of 198 transgender women were recruited by snowball sampling. A cross-sectional study was conducted through a structured questionnaire. Suicidal ideation, depression, and interpersonal needs were assessed. Path analysis was used to carry out the research goals and the mediating effect of depression was tested. There were nearly 37% of the participants reported lifetime suicidal ideation. Suicidal ideation was positively correlated with thwarted belongingness (t = -5.53, p < 0.01) and perceived burdensomeness (t = -5.02, p < 0.01). The direct effect from thwarted belongingness to suicidal ideation via depression was statistically significant (Std. β = 0.232, p < 0.01). Depression could also mediate the indirect path from perceived burdensomeness to suicidal ideation through depression (Std. β = 0.222, p < 0.01) although the direct path between them was not significant (Std. β = 0.046, p = 0.693). Depression fully mediated the relationship between perceived burdensomeness and suicidal ideation, and partially mediate the relationship between thwarted belongingness and suicidal ideation. To reduce the risk of suicidal ideation among transgender women, interventions targeting thwarted belongingness, perceived burdensomeness, and depression are needed.


Effects of epidermal growth factor and androgen influences on accessory sex glands in prepubertal Swiss-Webster mice.
The effects of epidermal growth factor (EGF) on androgen stimulation of accessory sex gland growth and biochemistry were determined for prepubertal male Swiss-Webster mice. For the seminal vesicle and anterior prostate, 5 alpha dihydrotestosterone (5 alpha DHT) treatment significantly increased the quantitative levels of organ wet weight, DNA content, polyamine content, and stereologically determined epithelium and lumen volumes above the control group. EGF treatment alone slightly enhanced the levels of most measured parameters from control values. However, when a combined EGF&5 alpha DHT treatment was compared with 5 alpha DHT treatment alone, the 5 alpha DHT treatment effects on epithelial and lumen volumes and polyamine content were antagonized by the action of EGF.


Thoracic endometriosis: a case report.
Thoracic endometriosis is a rare form of extrapelvic endometriosis. These patients typically present with catamenial pneumothorax or hemoptysis. Adequate clinical history coupled with HRCT helps in early diagnosis and appropriate management of thoracic endometriosis.


Detection of Active Mammalian GH31 α-Glucosidases in Health and Disease Using In-Class, Broad-Spectrum Activity-Based Probes.
The development of small molecule activity-based probes (ABPs) is an evolving and powerful area of chemistry. There is a major need for synthetically accessible and specific ABPs to advance our understanding of enzymes in health and disease. α-Glucosidases are involved in diverse physiological processes including carbohydrate assimilation in the gastrointestinal tract, glycoprotein processing in the endoplasmic reticulum (ER), and intralysosomal glycogen catabolism. Inherited deficiency of the lysosomal acid α-glucosidase (GAA) causes the lysosomal glycogen storage disorder, Pompe disease. Here, we design a synthetic route for fluorescent and biotin-modified ABPs for in vitro and in situ monitoring of α-glucosidases. We show, through mass spectrometry, gel electrophoresis, and X-ray crystallography, that α-glucopyranose configured cyclophellitol aziridines label distinct retaining α-glucosidases including GAA and ER α-glucosidase II, and that this labeling can be tuned by pH. We illustrate a direct diagnostic application in Pompe disease patient cells, and discuss how the probes may be further exploited for diverse applications.


Proliferation of renal interstitial cells following injury induced by ureteral obstruction.
The proliferation of renal interstitial cells was studied by the use of tritiated thymidine incorporation following unilateral ureteral obstruction in the rabbit. There was a nonuniform response with significant increase in nuclear labeling in the obstructed kidney in all zones at 24, 48, and 72 hours following obstruction with the exception of the inner medulla where the counts at 24 and 48 hours were not significantly different from sham-operated controls. The major labeling occurred in interstitial fibroblasts. Within the zones of high labeling (cortex and outer medulla) these cells were separated by widening of the intersittial space. In the zone of low labeling (inner medulla) the interstitial cells maintained their normal spatial relationships.


Acute pulmonary oedema. A complication of upper airway obstruction.
A case of postoperative laryngeal spasm is presented in which severe pulmonary oedema developed after the laryngeal spasm was relieved. The management is discussed and some suggestions for prevention of pulmonary oedema in similar circumstances made. The pathophysiology of pulmonary oedema after acute upper airway obstruction is described.


Lufenuron impact upon Anthonomus grandis Boheman (Coleoptera: Curculionidae) midgut and its reflection in gametogenesis.
The insecticide Match® (lufenuron), one of the main insect growth regulators used in pest control, has been presented as a viable alternative against the boll weevil, Anthonomus grandis (Coleoptera: Curculionidae), by inhibiting chitin synthesis. Thus, this study aimed to examine whether Match® interferes in the synthesis of the peritrophic matrix, leading to changes in the midgut epithelium, resulting in nutritional deficiency and reflecting, thereby, in the gametogenesis process of A. grandis. Floral cotton buds were immersed in the insecticide solution (800μL of Match®+200mL of distilled water) and offered to the adult insects. The midguts of the insects were evaluated after 24 and 120h after feeding. The gonads were evaluated after 120h. The results showed that Match®, in both evaluation periods, induced histopathological alterations such as disorganization, vacuolization and desquamation of the midgut epithelium; histochemical modifications in the distribution patterns of carbohydrates, although without quantitative changes; and a strong decrease in protein levels. No apoptosis were observed, however, there was an increase in the number of regenerative cell nests. In the testicles, a reduction in the amount of spermatozoids and reduced carbohydrate levels were observed, but no difference in protein levels. The ovarioles presented structural disorganization of follicular cells, yolk reduction and decrease in protein levels, however, no change in carbohydrates levels was noted. Therefore, it is concluded that Match® performs histopathologic and histochemical alterations in the midgut epithelium and the gonads of A. grandis adults, reflecting in the gametogenesis process, presenting itself as a promising tool in the management of this pest on cotton crops.


Innovative treatments for adults with obstructive sleep apnea.
Obstructive sleep apnea (OSA) affects one in five adult males and is associated with significant comorbidity, cognitive impairment, excessive daytime sleepiness, and reduced quality of life. For over 25 years, the primary treatment has been continuous positive airway pressure, which introduces a column of air that serves as a pneumatic splint for the upper airway, preventing the airway collapse that is the physiologic definition of this syndrome. However, issues with patient tolerance and unacceptable levels of treatment adherence motivated the exploration of other potential treatments. With greater understanding of the physiologic mechanisms associated with OSA, novel interventions have emerged in the last 5 years. The purpose of this article is to describe new treatments for OSA and associated complex sleep apnea. New approaches to complex sleep apnea have included adaptive servoventilation. There is increased literature on the contribution of behavioral interventions to improve adherence with continuous positive airway pressure that have proven quite effective. New non-surgical treatments include oral pressure devices, improved mandibular advancement devices, nasal expiratory positive airway pressure, and newer approaches to positional therapy. Recent innovations in surgical interventions have included laser-assisted uvulopalatoplasty, radiofrequency ablation, palatal implants, and electrical stimulation of the upper airway muscles. No drugs have been approved to treat OSA, but potential drug therapies have centered on increasing ventilatory drive, altering the arousal threshold, modifying loop gain (a dimensionless value quantifying the stability of the ventilatory control system), or preventing airway collapse by affecting the surface tension. An emerging approach is the application of cannabinoids to increase upper airway tone.


Guidelines of the International Headache Society for Controlled Clinical Trials in Idiopathic Intracranial Hypertension.
The quality of clinical trials is essential to advance treatment, inform regulatory decisions and meta-analysis. With the increased incidence of idiopathic intracranial hypertension and the emergence of clinical trials for novel therapies in this condition, the International Headache Society Guidelines for Controlled Clinical Trials in Idiopathic Intracranial Hypertension aims to establish guidelines for designing state-of-the-art controlled clinical trials for idiopathic intracranial hypertension.


Adjuvant interferon for early or late recurrence of hepatocellular carcinoma and mortality from hepatocellular carcinoma following curative treatment: A meta-analysis with comparison of different types of hepatitis.
Adjuvant interferon (IFN) therapy following curative treatment for hepatocellular carcinoma (HCC) has been extensively investigated; however, the clinical benefits with different hepatitis backgrounds remain unclear. Medline, Embase, PubMed and the Cochrane Library databases were searched to identify randomized trials and cohort studies that enrolled HCC patients who received curative surgery or ablation therapy followed by IFN and control subjects; the studies were required to include data on early or late recurrence and mortality rates of HCC. Hepatitis B virus (HBV) associated with HCC (HBV-HCC) and hepatitis C virus (HCV) associated with HCC (HCV-HCC) were separately analyzed and recurrence, mortality and clinicopathological factors were compared. A total of 14 studies (9 randomized trials and 5 cohort studies, including 1,385 patients in total) were eligible for meta-analysis. IFN was found to decrease mortality and early recurrence rates, but exerted no effect on late recurrence rate. The effect of IFN differed between HBV-HCC and HCV-HCC cases. In HCV-HCC, IFN significantly reduced mortality as well as recurrence rates. However, in HBV-HCC patients, IFN reduced mortality rather than recurrence rates, although it also reduced the recurrence rate in certain subgroups. In conclusion, the effect of adjuvant IFN on postoperative recurrence differed between HBV-HCC and HCV-HCC cases; therefore, different strategies with adjuvant IFN should be used to treat HCC with different hepatitis backgrounds.