Maternal serum ferritin and fetal growth.
To determine the relationship between maternal serum ferritin and concentrations and specific types of fetal growth restriction (FGR). Serum ferritin concentrations were measured at approximately 25 and 36 weeks' gestation in 480 multiparas with singleton fetuses who participated in a study of risk factors for repeated FGR. Asymmetric FGR was defined by low birth weight for gestational age criteria and a ponderal index less than 2.32, and symmetric FGR was defined by the same birth weight for gestational age criteria and a ponderal index of at least 2.32. Among 480 infants, 370 were appropriate for gestational age (AGA), 58 had asymmetric FGR, and 52 had symmetric FGR. Higher ferritin concentrations were associated with black race, maternal age 25 years or older, and smoking. Mothers of asymmetric-FGR infants had higher mean ferritin levels than mothers of AGA infants at 25 weeks' (38.0 versus 20.2 microg/L, P < .01) and 36 weeks' gestation (21.0 versus 13.3 microg/L, P < .01), whereas mothers of symmetric-FGR infants had significantly lower ferritin levels at 36 weeks (8.3 microg/L). For mothers with serum ferritin levels of at least 26 microg/L (highest quartile at 25 weeks), the adjusted odds ratio (OR) for asymmetric-FGR infants was 3.4, 95% confidence interval (CI) 1.6, 7.2. There was a similar association between the highest quartile of serum ferritin at 36 weeks (at least 20 microg/L) and asymmetric FGR (adjusted OR 2.7, 95% CI 1.3, 5.8). Women with serum ferritin levels less than 3 microg/L (lowest quartile at 36 weeks) had an adjusted OR for symmetric-FGR infants of 2.2, 95% CI 1.01, 4.6. High maternal serum ferritin levels are associated with asymmetric FGR, whereas low serum ferritin levels are associated with symmetric FGR.


Cytoplasmic regions adjacent to the M3 and M4 transmembrane segments influence expression and function of alpha7 nicotinic acetylcholine receptors. A study with single amino acid mutants.
We studied the role of the cytoplasmic regions adjacent to the M3 and M4 transmembrane segments of alpha7 nicotinic receptors in the expression of functional channels. For this purpose, a total of 50 amino acids were mutated throughout the mentioned regions. Mutants close to M3, from Arg294 to Leu321, showed slight modifications in the levels of alpha-bungarotoxin binding sites and acetylcholine-evoked currents. Exceptions were mutants located at two clusters (His296 to Pro300 and Ile312 to Trp316), which exhibited low expression levels. In addition, some mutants showed altered functional responses. Many mutants close to M4 showed increased receptor expression, especially the ones located at the hydrophobic face of a putative amphipathic helix. This effect seems to be the consequence of a combination of increased receptor biosynthesis, higher transport efficiency and delayed degradation, such that we postulate that elements in the amphipathic domain strongly influence receptor stability. Finally, some mutants in this region showed altered functional responses: elimination of positively charged residues (Arg424 and Arg426) increased currents, whereas the opposite was observed upon suppression of negatively charged ones (Glu430 and Glu432). These results suggest that the cytoplasmic regions close to M3 and M4 play important structural and functional roles.


Expression of adrenocorticotropin receptor gene in adrenocortical adenomas from patients with Cushing syndrome: possible contribution for the autonomous production of cortisol.
To examine whether inhibition of endogenous adrenocorticotropin (ACTH) secretion in patients with Cushing syndrome affects the expression of the ACTH receptor (ACTH-R) gene in adrenocortical adenoma and attached atrophic normal gland. ACTH increases adrenal cell growth and steroidogenesis by means of ACTH-R. In vivo and in vitro studies have shown that expression of ACTH-R is upregulated by its own ligand ACTH in several species. In patients with Cushing syndrome resulting from adrenocortical adenoma, there is autonomous production of cortisol from the adenoma. This strongly inhibits endogenous ACTH secretion, giving rise to the speculation that the expression of the ACTH-R gene in these patients is also suppressed. However, previous studies have shown that administration of exogenous ACTH to these patients leads to a further increase in the production of cortisol, suggesting the expression of functional ACTH-R in the adenoma. The authors, therefore, examined the expression of the ACTH-R gene in these patients. Fourteen patients with Cushing syndrome were studied. Glucocorticoid excess resulting from autonomous production from the adenomas was ascertained, and unilateral adrenalectomy was performed. The levels of ACTH-R and cytochrome P450 side chain cleavage enzyme (P450scc) mRNAs were determined by Northern blot analysis. The entire coding region of the ACTH-R gene in these patients was sequenced. ACTH-R mRNA abundance in the attached atrophic normal adrenals was suppressed and invariably less than that in the normal gland obtained from a patient with renal cancer. However, the expression of ACTH-R mRNA was not suppressed in any of the adenomas. Expression of ACTH-R mRNA in the adenomas was four- to sixfold greater than that in the attached atrophic gland. No mutation in the coding sequence of the ACTH-R gene in the adenoma was detected in any of the patients. The mRNA in the adenomas appeared to be translated into functionally active receptor because intramuscular administration of ACTH resulted in significant increases in plasma cortisol before surgery but not 3 months after surgery. In addition, there was a positive linear correlation between the expressions of ACTH-R and P450scc mRNAs in the adenoma tissue. Suppressed ACTH secretion in patients with Cushing syndrome results in reduction of the ACTH-R mRNA expression in nonneoplastic adrenocortical cells. However, the regulatory mechanism of ACTH-R expression might be different in adenoma. Persistent expression in the adenoma of ACTH-R alone, even in the absence of ACTH, might result in increased basal adenyl cyclase activity, as observed in the case of thyroid-stimulating hormone receptor, and thereby might play a role in the autonomous production of cortisol.


Epigallocatechin gallate (EGCG) alters body fat and lean mass through sex-dependent metabolic mechanisms in Drosophila melanogaster.
There is increasing interest in the potential role of epigallocatechin gallate (EGCG) in changing body composition to lower body fat with increased lean mass. In this study, we examined the sex-dependent effect of EGCG on body composition, locomotion, feeding behaviour, sugar levels, and transcription levels of key regulators in lipid, carbohydrate, and energy metabolisms in Drosophila melanogaster. EGCG had no effects on body weights in both females and males, but decreased fat accumulation in females compared to the control, accompanied by a reduction in food intake. EGCG treatments increased lean mass and locomotor activity, and downregulated transcription levels of brummer (bmm), adipokinetic hormone (akh), and Drosophila insulin-like peptide 2 (dilp2), and upregulated spargel (srl) in males. In addition, EGCG decreased sugar levels in both females and males. In conclusion, EGCG promotes lean phenotype in D. melanogaster via sex-specific metabolic regulations.


On-line measurements of K+ activity in the tensile water of the xylem conduit of higher plants.
In higher plants the xylem is the main pathway for anti-gravitational, long-distance transport of nutrients and water from the root through the shoot to the upper leaves. In the xylem conduit water is in a metastable state if tension larger than 0.1 MPa (i.e. negative pressure) is developed. While diurnal changes in negative pressure of individual xylem vessels can quite accurately be recorded by the minimal-invasive xylem pressure probe technique and water flow by non-invasive NMR techniques, the problem of continuous monitoring of solute flow remains a hitherto unresolved challenge. As shown here, integration of a K+ selective and a potential measuring microelectrode into the xylem pressure probe allowed on-line measurements of the K+ activity in individual xylem vessels of maize roots together with pressure and trans-root potential, the potential difference between the xylem and the external medium (i.e. the overall driving force of ions through the root tissue). When light irradiation was increased from 10 micro mol m(-2) s(-1) to 300 micro mol m(-2) s(-1) and negative pressure developed in the vessel, xylem K+ activity dropped from 3.6 +/- 2.6 mm to 0.9 +/- 0.7 mm (n = 16), whereas the trans-root potential depolarized from -2 +/- 11 mV to + 12 +/- 11 mV (n = 11), i.e. by + 14 +/- 7 mV. The effect of light on all three parameters was reversible. Exposure of the root to various K+ activities in the bath ranging from 0.1 to 43 mm revealed that the K+ activity of the xylem sap was shielded against short-term fluctuations in K+ supply to a large extent. In contrast, control experiments in which the root was cut 1 cm below the probe insertion point, allowing direct entry of external K+ into the xylem vessels, demonstrated that the xylem equilibrated rapidly with external K+. This was taken simultaneously as a proof for the correct reading of the probe.


Striatal function in relation to negative symptoms in schizophrenia.
Previous studies have suggested that motivational aspects of executive functioning, which may be disrupted in schizophrenia patients with negative symptoms, are mediated in part by the striatum. Negative symptoms have been linked to impaired recruitment of both the striatum and the dorsolateral prefrontal cortex (DLPFC). Here we tested the hypothesis that negative symptoms are associated primarily with striatal dysfunction, using functional magnetic resonance imaging (fMRI). Working-memory load-dependent activation and gray matter volumes of the striatum and DLPFC were measured using a region-of-interest (ROI) approach, in 147 schizophrenia patients and 160 healthy controls. In addition to testing for a linear relationships between striatal function and negative symptoms, we chose a second, categorical analytic strategy in which we compared three demographically and behaviorally matched subgroups: patients with a high burden of negative symptoms, patients with minimal negative symptoms, and healthy subjects. There were no differences in striatal response magnitudes between schizophrenia patients and healthy controls, but right DLPFC activity was higher in patients than in controls. Negative symptoms were inversely associated with striatal, but not DLPFC, activity. In addition, patients with a high burden of negative symptoms exhibited significantly lower bilateral striatal, but not DLPFC, activation than schizophrenia patients with minimal negative symptoms. Working memory performance, antipsychotic exposure and changes in gray matter volumes did not account for these differences. These data provide further evidence for a robust association between negative symptoms and diminished striatal activity. Future work will determine whether low striatal activity in schizophrenia patients could serve as a reliable biomarker for negative symptoms.


Thyroid cell responses to thyrotropin and 12-O-tetradecanoyl-phorbol-13-acetate: translocation of protein kinase C and phosphorylation of thyroid cell polypeptide substrates.
Not all of the effects of thyroid-stimulating hormone (TSH) on the thyroid are mediated by activation of the adenylate cyclase-cyclic AMP system, indicating that other control systems must also exist. Although a calcium-phospholipid-dependent protein kinase (protein kinase C) and specific substrates had been identified in thyroid tissue, their responsiveness to TSH and other stimulators has not been determined. In thyroid cells which had been preloaded with [32P]orthophosphate, TSH and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) increased the phosphorylation of a 33K polypeptide substrate within 5 min in a dose-dependent fashion. The effect was observed with 1 mU/ml TSH and 3 nM TPA and was maximal with 100 mU/ml TSH and 100 nM TPA. The biologically inactive analog of TPA, 4 alpha-phorbol, had no effect. Isobutylmethylxanthine (IBMX) decreased the phosphorylation of the 33K polypeptide and inhibited the effect of TSH and TPA, indicating that the phosphorylation is not mediated by cyclic AMP. TSH and IBMX, but not TPA, augmented phosphorylation of a 38K polypeptide, suggesting involvement of cyclic AMP. In contrast TPA, but not TSH, increased the phosphorylation of 58K and 28K polypeptides. TSH, but not TPA or 4 alpha-phorbol, elevated the cyclic AMP level of thyroid slices. Incubation of thyroid slices with TSH or TPA significantly decreased protein kinase C activity in the 100,000g cytosol fraction and increased it in an extract of plasma membranes. The effect was present within 5 min and was maximal by 30 min. The effect was observed with 100 mU/ml TSH or 1 nM TPA. The stimulation by TSH or TPA of protein kinase C and its translocation from the cytosol to the plasma membranes of thyroid tissue may provide another mechanism for control of thyroid cell metabolism.


[Preventive vocational measures for adolescents with asthma and allergies--a model project].
The difficulties encountered by asthmatic and allergic youngsters faced with choosing a career represent a problem that is gaining in relevance. The general prohibition of certain trades is, for many of those involved, both unsatisfactory and lacing in future prospects. In a model project supported by the Federal Institute of Labour is intended to help young people with asthma and allergies. By means of an interdisciplinary programme involving psychologists, teachers, instructors and physicians, the youngsters are given advice on how to chose a career/profession on the basis of their personal interests, abilities, job suitability and health situation. Between September 1987 and March 1989, 50 persons, including 43 asthmatics participated in this programme. In contrast to the poor level of schooling, the intelligence test revealed a normal distribution. The psychological stress tolerance was reduced in two-thirds of the subjects. In 7 cases, workplace-associated changes in pulmonary function were established; in 11 cases workplace-related dermatological problems were seen. Only one-third of the youngsters were considered suitable for careers in industry; the majority were advised to take advantage of the training or rehabilitation possibilities offered by the Federal Institute of Labour.


Vagus nerve stimulation acutely alters food craving in adults with depression.
Vagus nerve stimulation (VNS) is now available as a treatment for epilepsy and treatment-resistant depression. The vagus nerve plays a central role in satiety and short-term regulation of food intake and research suggests a relationship between VNS and weight loss. The underlying mechanisms of this relationship are unknown. The purpose of the current study was to determine whether acute cervical VNS might temporarily alter food cravings. Thirty-three participants were recruited for three groups; depression VNS, depression non-VNS, and healthy controls. Participants viewed 22 computerized images of foods twice in one session and completed ratings for food cravings after each image. The VNS participants' devices were turned on for one viewing of an image and off for the other (randomized order). Participants were blind to VNS condition (on versus off). Acute VNS device activation was associated with a significant change in cravings-ratings for sweet foods. A significant proportion of variability in VNS-related changes in cravings was accounted for by patients' clinical VNS device settings, acute level of depression, and body mass. Further studies are warranted addressing how acute or chronic VNS might modify eating behavior and weight.


Treatment of metastatic breast cancer in estrogen receptor positive patients. A randomized trial comparing tamoxifen alone versus tamoxifen plus CMF.
In a controlled clinical trial, 52 patients with ER positive metastatic breast cancer were randomly assigned to receive initial treatment with either tamoxifen alone followed by sequential cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) after tumour progression of concurrent tamoxifen plus CMF, All 52 patients entered are eligible and 50 patients were currently assessable. Response rates (CR + PR) were similar for the two treatment groups (15/24 tamoxifen alone, 17/26 tamoxifen + CMF). The median durations of survival for the two treatment groups 17.7 months and 17.1 months were also not significantly different. Significant correlations were found between level of ER and response rate and also between level of ER and response duration. From the result of this investigation it would appear that there is no advantage to the addition of chemotherapy prior to an adequate trial of hormone therapy in patients with metastatic ER positive breast cancer.


[Comparative study of the effect of different cryoprotectants on desmoglein 1 in human skin].
To compare the effects of two different cryoprotectants on human desmoglein 1 (Dsg 1), and to provide experimental basis for the optimization of cryoprotectant. Five donated thin split-thickness skin grafts were used, and the experiment was conducted within 4 hours after skin grafts harvest. The skin grafts were divided into 3 groups: group A (n = 2) in which skin grafts were immersed in 0.5 mol/L trehalose/DMSO; group B (n = 2) in which skin grafts were immersed in DMSO/propanediol; group C (n = 1) in which fresh skin graft received no further treatment. Groups A and B were stored in -196 degree C liquid nitrogen for 7 and 21 days, respectively, and then underwent experiment. Immunohistochemistry staining observation was performed on each group, RT-PCR method was used to detect the expression of Dsg 1 in skin. The immunohistochemistry staining showed that the protein in groups A and B was stained brown-yellow and distributed evenly 7 days after cryopreservation; the expression signal of epidermal basal cell was similar to that of group C; absorbance (A) value of groups A, B and C was 0.285 +/- 0.006, 0.284 +/- 0.004 and 0.287 +/- 0.008, respectively, suggesting there was no significant difference between groups A and B and group C (P > 0.05). At 21 days after cryopreservation, the expression of positive cells in group B decreased; no obvious decrease was observed in group A, A value of groups A and B was 0.282 +/- 0.004 and 0.275 +/- 0.005, respectively, indicating there was a significant difference between group B and groups A and C (P < 0.05). RT-PCR detection showed that A value of groups A and B at 7 days after cryopreservation was 0.810 +/- 0.012 and 0.803 +/- 0.008, respectively; A value of groups A and B at 21 days after cryopreservation was 0.806 +/- 0.008 and 0.782 +/- 0.013, respectively; and the A value of group C was 0.814 +/- 0.012, indicating there was significant difference between group B and groups A and C at 21 days after cryopreservation (p < 0.05), and no significant differences among groups were noted at other time points (P > 0.05). Trehalose/DMSO is better than traditional cryoprotectant DMSO/propanediol in protecting Dsg 1 of human skin.


Hydroxychloroquine for the prevention of acute graft-versus-host disease after unrelated donor transplantation.
Hydroxychloroquine (HCQ) is an immunosuppressive agent that interferes with antigen presentation and with activity against graft-versus-host disease (GVHD). In a phase II trial assessing the GVHD prophylactic effects of HCQ, 51 consecutive unrelated donor transplant recipients received HCQ in addition to cyclosporin A, methylprednisolone, and methotrexate. HCQ was initiated on pretransplantation day -21 at 800 mg/d and continued until day +100 after transplantation. HCQ was extremely well tolerated and was not associated with side effects. Pharmacokinetic analyses demonstrated large inter- and intrapatient variability. The addition of HCQ did not affect posttransplantation immune recovery. Grade II to IV acute GVHD was observed in 56% of patients, and grade III and IV GVHD was observed in 17%. Day +100 mortality was 22%. When compared with a matched cohort of patients reported to the International Bone Marrow Transplant Registry, patients receiving HCQ had comparable cumulative incidences of grade II to IV acute GVHD. However, lower incidences of grades III and IV GVHD and better GVHD-free survival were observed in HCQ-treated patients (P =.01). We conclude that prophylactic HCQ is well tolerated and associated with a low incidence of severe acute GVHD. An ongoing placebo-controlled randomized trial will further determine what role HCQ plays in preventing GVHD after allografting.


Recovery: what mental health nurses and service users say about the concept of recovery.
This study presents a thematic analysis of focus group talk to examine what recovery in mental health means to service users and nurses. Data were collected from two focus groups, one group of service users and one group of nurses. The service user group (n=6) were adults with previous or recent experience of inpatient mental health services. The nursing group were registered nurses (n=5) of various grades and experience currently working in inpatient mental health services in one region of the U.K. Thematic analysis using Krueger and Casey's framework led to four themes being developed. These were 'understandings of recovery', 'semantics', 'therapeutics' and 'a journey'. While the recovery concept was not new to either group, understandings of recovery were vague and contradictory.


Characterization of the estradiol-binding site structure of human protein disulfide isomerase (PDI).
Earlier studies showed that 17β-estradiol (E(2)), an endogenous female sex hormone, can bind to human protein disulfide isomerase (PDI), a protein folding catalyst for disulfide bond formation and rearrangement. This binding interaction can modulate the intracellular levels of E(2) and its biological actions. However, the structure of PDI's E(2)-binding site is still unclear at present, which is the focus of this study. The E(2)-binding site structure of human PDI was studied by using various biochemical approaches coupled with radiometric receptor-binding assays, site-directed mutagenesis, and molecular computational modeling. Analysis of various PDI protein fragments showed that the [(3)H]E(2)-binding activity is not associated with the single b or b' domain but is associated with the b-b' domain combination. Computational docking analyses predicted that the E(2)-binding site is located in a hydrophobic pocket composed mainly of the b' domain and partially of the b domain. A hydrogen bond, formed between the 3-hydroxyl group of E(2) and His256 of PDI is critical for the binding interaction. This binding model was jointly confirmed by a series of detailed experiments, including site-directed mutagenesis of the His256 residue coupled with selective modifications of the ligand structures to alter the binding interaction. The results of this study elucidated the structural basis for the PDI-E(2) binding interaction and the reservoir role of PDI in modulating the intracellular E(2) levels. The identified PDI E(2)-binding site is quite different from its known peptide binding sites. Given that PDI is a potential therapeutic target for cancer chemotherapy and HIV prevention and that E(2) can inhibit PDI activity in vitro, the E(2)-binding site structure of human PDI determined here offers structural insights which may aid in the rational design of novel PDI inhibitors.


Economic recession and mental health: an overview.
Effects of the current global economic downturn on population mental health will emerge in the years ahead. Judging from earlier experience of financial crises in various parts of the world, stresses associated with rising unemployment, poverty and social insecurity will lead to upward trends in many national suicide rates, as well as to less readily charted increase in the prevalence of psychiatric illness, alcohol-related disorders and illicit drug use. At the same time, mental health services are being cut back as part of government austerity programs. Budget cuts will thus affect psychiatric services adversely just when economic stressors are raising the levels of need and demand in affected populations. Proactive fiscal and social policies could, however, help to mitigate the health consequences of recession. Evidence- based preventive measures include active labor market and family support programs, regulation of alcohol prices and availability, community care for known high-risk groups, and debt relief projects. Economic mental health care could best be achieved, not by decimating services but by planning and deploying these to meet the needs of defined area populations.


Facing away: mental health treatment with the Old Order Amish.
Mental health treatment of the Old Order Amish is a relatively new phenomenon. Increasingly however, members of this sequestered Christian sect are either voluntarily seeking treatment or finding themselves ordered into treatment. Because they resist acculturation, many of the models of cross-cultural treatment are less than fully applicable; and because their pursuit of counseling is relatively recent, there is little information available to guide the therapist working with these clients. This article provides a practical approach to the more salient experiences and difficulties that arise in treatment of the Old Order Amish.


Genome-Wide Characterization of Simple Sequence Repeat (SSR) Loci in Chinese Jujube and Jujube SSR Primer Transferability.
Chinese jujube (Ziziphus jujuba), an economically important species in the Rhamnaceae family, is a popular fruit tree in Asia. Here, we surveyed and characterized simple sequence repeats (SSRs) in the jujube genome. A total of 436,676 SSR loci were identified, with an average distance of 0.93 Kb between the loci. A large proportion of the SSRs included mononucleotide, dinucleotide and trinucleotide repeat motifs, which accounted for 64.87%, 24.40%, and 8.74% of all repeats, respectively. Among the mononucleotide repeats, A/T was the most common, whereas AT/TA was the most common dinucleotide repeat. A total of 30,565 primer pairs were successfully designed and screened using a series of criteria. Moreover, 725 of 1,000 randomly selected primer pairs were effective among 6 cultivars, and 511 of these primer pairs were polymorphic. Sequencing the amplicons of two SSRs across three jujube cultivars revealed variations in the repeats. The transferability of jujube SSR primers proved that 35/64 SSRs could be transferred across family boundary. Using jujube SSR primers, clustering analysis results from 15 species were highly consistent with the Angiosperm Phylogeny Group (APGIII) System. The genome-wide characterization of SSRs in Chinese jujube is very valuable for whole-genome characterization and marker-assisted selection in jujube breeding. In addition, the transferability of jujube SSR primers could provide a solid foundation for their further utilization.


IL1RAPL1 controls inhibitory networks during cerebellar development in mice.
Abnormalities in the formation and function of cerebellar circuitry potentially contribute to cognitive deficits in humans. In the adult, the activity of the sole output neurons of the cerebellar cortex - the Purkinje cells (PCs) - is shaped by the balance of activity between local excitatory and inhibitory circuits. However, how this balance is established during development remains poorly understood. Here, we investigate the role of interleukin-1 receptor accessory protein-like 1 (IL1RAPL1), a protein linked to cognitive function which interacts with neuronal calcium sensor 1 (NCS-1) in the development of mouse cerebellum. Using Il1rapl1-deficient mice, we found that absence of IL1RAPL1 causes a transient disinhibition of deep cerebellar nuclei neurons between postnatal days 10 and 14 (P10/P14). Upstream, in the cerebellar cortex, we found developmental perturbations in the activity level of molecular layer interneurons (MLIs), resulting in the premature appearance of giant GABAA-mediated inhibitory post-synaptic currents capable of silencing PCs. Examination of feed-forward recruitment of MLIs by parallel fibres shows that during this P10/P14 time window, MLIs were more responsive to incoming excitatory drive. Thus, we conclude that IL1RAPL1 exerts a key function during cerebellar development in establishing local excitation/inhibition balance.


Evaluating the durability and performance of polyoxometalate-ionic liquid coatings on calcareous stones: Preventing biocolonisation in outdoor environments.
Rock-based materials exposed to outdoor environments are naturally colonised by an array of microorganisms, which can cause dissolution and fracturing of the natural stone. Biocolonisation of monuments and architectures of important cultural heritage therefore represents an expensive and recurring problem for local authorities and private owners alike. In this area, preventive strategies to mitigate biocolonisation are generally preferred to curative approaches, such as mechanical cleaning by brush or high-pressure cleaning, to remove pre-existing patina. The aim of this work was to study the interaction between biocidal polyoxometalate-ionic liquid (POM-IL) coatings and calcareous stones and evaluate the capacity of these coatings to prevent biocolonisation through a series of accelerated ageing studies in climate chambers, carried out in parallel with a two-year period of outdoor exposure in north-eastern France. Our experiments show that POM-IL coatings did not affect water vapour transfer nor significantly alter the total porosity of the calcareous stones. Simulated weathering studies replicating harsh (hot and wet) climatic weather conditions demonstrated that the colour variation of POM-IL-coated stones did not vary significantly with respect to the natural uncoated stones. Accelerated biocolonisation studies performed on the weathered POM-IL-coated stones proved that the coatings were still capable of preventing colonisation by an algal biofilm. However, a combination of colour measurements, chlorophyll fluorescence data, and scanning electron microscopy imaging of stones aged outdoors in northern France for two years showed that coated and uncoated stone samples showed signs of colonisation by fungal mycelium and phototrophs. Altogether, our results demonstrate that POM-ILs are suitable as preventative biocidal coatings for calcareous stones, but the correct concentrations must be chosen to achieve a balance between porosity of the stone, the resulting colour variation and the desired duration of the biocidal effect over longer periods of time, particularly in outdoor environments.


Use of recombinant bovine somatotropin for up to two consecutive lactations on dairy production traits.
Fifteen (control) cows were injected with saline; 28 cows were treated with rbST (15 with 10.3 and 13 with 20.6 mg/d). Fourteen of the 28 treated cows had between injected with rbST in the previous lactation. A total of 29 cows in the present trial had not received rbST in previous lactation. Treatment injections were started between wk 4 and 5 of lactation and continued for 266 consecutive days. Milk production, fee intake and efficiency, and BW data were recorded for 3 wk before and 3 wk after a 38-wk rbST treatment period. Administration of rbST increased average FCM yields in the current lactation by 19%, increased feed energy intake by 7%, and decreased feed conversion (energy intake per unit FCM output) by 17%. Previous treatment with rbST did not significantly affect current milk production but caused a nonsignificant increase in feed intake and a significant, unfavorable, increase in feed conversion of 12%. The results suggest that the advantages of rbST in terms of increased milk yield are maintained for a second consecutive lactation of rbST administration. However, the advantages of rbST in terms of improved feed conversion may be substantially reduced in a second consecutive lactation of administration.


[Structure-activity relationship of ceftazidime. Consequences on the bacterial spectrum].
The structure-activity relationships of antibiotics are currently known, especially for cephalosporins. Ceftazidime, which is a new semi-synthetic drug, possesses as side chains an aminothiazole ring and a propylcarboxy moiety at position 7, and at position 3 a pyridine group similar to that of cephaloridine: these structural modifications of the cephalosporin nucleus confer upon ceftazidime increased affinity for penicillin-binding-proteins of Gram negative bacilli, a high stability to beta-lactamases and an enlarged spectrum of antibacterial activity including Pseudomonas and Acinetobacter. The presence at position 3 of a pyridine group is responsible for a rapid intrabacterial penetration of ceftazidime and for favourable pharmacokinetic properties.


Radiochemical, Computational, and Spectroscopic Evaluation of High-Denticity Desferrioxamine Derivatives DFO2 and DFO2p toward an Ideal Zirconium-89 Chelate Platform.
Desferrioxamine (DFO) has long been considered the gold standard chelator for incorporating [89Zr]Zr4+ in radiopharmaceuticals for positron emission tomography (PET) imaging. To improve the stability of DFO with zirconium-89 and to expand its coordination sphere to enable binding of large therapeutic radiometals, we have synthesized the highest denticity DFO derivatives to date: dodecadentate DFO2 and DFO2p. In this study, we describe the synthesis and characterization of a novel DFO-based chelator, DFO2p, which is comprised of two DFO strands connected by an p-NO2-phenyl linker and therefore contains double the chelating moieties of DFO (potential coordination number up to 12 vs 6). The chelator DFO2p offers an optimized synthesis comprised of only a single reaction step and improves water solubility relative to DFO2, but the shorter linker reduces molecular flexibility. Both DFO2 and DFO2p, each with 6 potential hydroxamate ligands, are able to reach a more energetically favorable 8-coordinate environment for Zr(IV) than DFO. The zirconium(IV) coordination environment of these complexes were evaluated by a combination of density functional theory (DFT) calculations and synchrotron spectroscopy (extended X-ray absorption fine structure), which suggest the inner-coordination sphere of zirconium(IV) to be comprised of the outermost four hydroxamate ligands. These results also confirm a single Zr(IV) in each chelator, and the hydroxide ligands which complete the coordination sphere of Zr(IV)-DFO are absent from Zr(IV)-DFO2 and Zr(IV)-DFO2p. Radiochemical stability studies with zirconium-89 revealed the order of real-world stability to be DFO2 > DFO2p ≫ DFO. The zirconium-89 complexes of these new high-denticity chelators were found to be far more stable than DFO, and the decreased molecular flexibility of DFO2p, relative to DFO2, could explain its decreased stability, relative to DFO2.


[Antagonism of microbial population of protective flora and its relation to microbiocenosis and nutritional factors].
Total antagonistic activity (TAA) of the populations of bifidobacteria, lactobacilli, enterobacteria was considered in relation to the method of its evaluation which has been modified, criteria of TAA assessment permitting its measurements in per cents. The technique proposed bases on determination of the metabolites capable of inhibiting pathogenic and opportunistic bacteria and provides information on the action of alimentary factors under study on the function of intestinal microbiocenosis. The factors may produce a multidirectional effect on the structure and biological activity of the microbial populations. The method can work to characterize microbiocenosis both in normal and pathological conditions, to evaluate efficacy of specially devised food products.


A Selective Ratiometric Fluorescent Probe for No-Wash Detection of PVC Microplastic.
Microplastics (MP) are micrometric plastic particles present in drinking water, food and the environment that constitute an emerging pollutant and pose a menace to human health. Novel methods for the fast detection of these new contaminants are needed. Fluorescence-based detection exploits the use of specific probes to label the MP particles. This method can be environmentally friendly, low-cost, easily scalable but also very sensitive and specific. Here, we present the synthesis and application of a new probe based on perylene-diimide (PDI), which can be prepared in a few minutes by a one-pot reaction using a conventional microwave oven and can be used for the direct detection of MP in water without any further treatment of the sample. The green fluorescence is strongly quenched in water at neutral pH because of the formation dimers. The ability of the probe to label MP was tested for polyvinyl chloride (PVC), polyethylene (PE), polyethylene terephthalate (PET), polypropylene (PP), polystyrene (PS), poly methyl methacrylate (PMMA) and polytetrafluoroethylene (PTFE). The probe showed considerable selectivity to PVC MP, which presented an intense red emission after staining. Interestingly, the fluorescence of the MP after labeling could be detected, under excitation with a blue diode, with a conventional CMOS color camera. Good selectivity was achieved analyzing the red to green fluorescence intensity ratio. UV-Vis absorption, steady-state and time-resolved fluorescence spectroscopy, fluorescence anisotropy, fluorescence wide-field and confocal laser scanning microscopy allowed elucidating the mechanism of the staining in detail.


Medicine in colonial Australia, 1788-1900.
For the first five decades of European settlement in Australia, medical care for convicts and free settlers was provided by the Colonial Medical Service. After about 1850, as population and wealth grew markedly, there was significant professional development based on private practice. Except in Victoria, medical societies and journals did not become solidly established until late in the 19th century. The advent of local British Medical Association branches was an important factor in this consolidation. In the first few years of the colony, mortality was very high, but the common childhood infections were absent until the 1830s. From the 1880s, there was a sustained decline in mortality from communicable diseases, and therefore in aggregate mortality, while maternal mortality remained high. Australian practitioners quickly took up advances in practice from overseas, such as antisepsis and diphtheria antitoxin. They shared in the international growth in the status of medicine, which was conferred by the achievements of bacteriology in particular. From 1813, students were apprenticed in Sydney and Hobart and then travelled to Britain to obtain corporate qualifications. Medical schools were ultimately opened in the new universities in Melbourne (in 1862), Sydney (1883) and Adelaide (1885). The first female student was admitted to medicine in Sydney in 1885. Medical politics were intense. The outlawing of practice by unorthodox practitioners proved to be an unattainable goal. In the latter half of the 19th century, doctors saw chemists as unfair competitors for patients. The main medicopolitical struggle was with the mutual-aid friendly societies, which funded basic medical care for a significant proportion of the population until well into the 20th century. The organised profession set out to overcome the power of the lay-controlled societies in imposing an unacceptable contract system on doctors, even if, historically, the guaranteed income was a sine qua non of practice in poorer areas.


Challenges in implementing HIV laboratory monitoring in resource-constrained settings: how to do more with less.
Laboratory monitoring for HIV disease in resource-limited settings has now become one of the key challenges for antiretroviral treatment (ART) access and success, as emphasized by the 2010 revised WHO guidelines for ART in resource-limited settings. Thus, the most common method for initiating ART, and monitoring treatment response in resource-constrained environments is the measurement of CD4 T-cell count. Affordable CD4 T-cell counting has gradually been made possible by using simple, compact and robust, low-cost, new-generation cytometers, operating as single-platform volumetric instruments. Several cost-effective point-of-care CD4 T-cell testing options are also already on the market, in order to improve access to CD4 T-cell monitoring, especially for rural patients, and to reduce loss-to-follow-up of patients. In addition, HIV RNA viral load measurement is becoming increasingly important, mainly for a systematic confirmation of first-line ART failure before switching to second-line treatment to avoid belated as well as premature therapeutic decisions and their potentially negative consequences. Viral load testing should now be considered as the standard of care for therapeutic failure in all resource-limited settings. However, the measurement of HIV viral load remains a centralized marker, carried out in a limited number of reference laboratories. Finally, the costs of second-line ART regimens, rather than the laboratory test costs themselves, currently constitute the primary determinant of the total cost in ART switching. Laboratory monitoring strategies may become more attractive as price negotiations render second-line ART regimens less expensive worldwide.


The ultrafast pixel array camera system and its applications in high energy density physics.
Diagnostics in high energy density physics, shock physics, and related fields are primarily driven by a need to record rapidly time-evolving signals in single-shot events. These measurements are often limited by channel count and signal degradation issues on cable links between the detector and digitizer. We present the Ultrafast Pixel Array Camera (UPAC), a compact and flexible detector readout system with 32 waveform-recording channels at up to 10 Gsample/s and 1.8 GHz analog bandwidth. The compact footprint allows the UPAC to be directly embedded in the detector environment. A key enabling technology is the PSEC4A chip, an eight-channel switch-capacitor array sampling device with up to 1056 samples/channel. The UPAC system includes a high-density input connector that can plug directly into an application-specific detector board, programmable control, and serial readout, with less than 5 W of power consumption in full operation. We present the UPAC design and characterization, including a measured timing resolution of ∼20 ps or better on acquisitions of sub-nanosecond pulses with minimal system calibrations. Example applications of the UPAC are also shown to demonstrate operation of a solid-state streak camera, an ultrafast imaging array, and a neutron time-of-flight spectrometer.


Mechanism of coarsening and bubble formation in high-genus nanoporous metals.
Coarsening of crystalline nanoporous metals involves complex changes in topology associated with the reduction of genus via both ligament pinch-off and void bubble formation. Although void bubbles in metals are often associated with vacancy agglomeration, we use large-scale kinetic Monte Carlo simulations to show that both bubble formation and ligament pinch-off are natural results of a surface-diffusion-controlled solid-state Rayleigh instability that controls changes in the topology of the porous material during coarsening. This result is used to find an effective activation energy for coarsening in nanoporous metals that is associated with the reduction of topological genus, and not the reduction of local surface roughness.


Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion.
AMPK plays a central role in influencing fuel usage and selection. The aim of this study was to analyze the impact of low-dose AMP analog 5-aminoimidazole-4-carboxamide-1-beta-d-ribosyl monophosphate (ZMP) on whole body glucose turnover and skeletal muscle (SkM) glucose metabolism. Dogs were restudied after prior 48-h fatty acid oxidation (FA(OX)) blockade by methylpalmoxirate (MP; 5 x 12 hourly 10 mg/kg doses). During the basal equilibrium period (0-150 min), fasting dogs (n = 8) were infused with [3-(3)H]glucose followed by either 2-h saline or AICAR (1.5-2.0 mg x kg(-1) x min(-1)) infusions. SkM was biopsied at completion of each study. On a separate day, the same protocol was undertaken after 48-h in vivo FA(OX) blockade. The AICAR and AICAR + MP studies were repeated in three chronic alloxan-diabetic dogs. AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA). Parallel increases in hepatic glucose production (HGP), glucose disappearance (R(d tissue)), and glycolytic flux (GF) occurred, whereas metabolic clearance rate of glucose (MCR(g)) did not change significantly. Intracellular SkM glucose, glucose 6-phosphate, and glycogen were unchanged. Acetyl-CoA carboxylase (ACC approximately pSer(221)) increased by 50%. In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and R(d tissue) responses were markedly attenuated, but MCR(g) and GF increased significantly. SkM substrates were unchanged, but ACC approximately pSer(221) rose by 80%. Thus low-dose AICAR leads to increases in HGP and SkM glucose uptake, which are modified by prior FA(ox) blockade.


Noninvasive imaging, treatment, and microscopic confirmation of clearance of basal cell carcinoma.
The diagnosis of basal cell carcinoma (BCC) is generally established by skin biopsy followed by tissue preparation and microscopic analysis. Treatment of BCC is often accomplished by surgical excision. To confirm the presence of BCC with a noninvasive imaging technique, to treat the patient with a topical immune response modifier, and to confirm the clearance of BCC noninvasively. Confocal microscopy (CM) is a noninvasive technique for real-time imaging of skin in vivo. Imiquimod, an immune response modifier, is applied topically by the patient to the skin lesion. The presence of BCC was confirmed with CM. Posttreatment CM imaging confirmed the clearance of BCC from the entire treatment field. Both the pretreatment and the posttreatment CM findings were confirmed by invasive biopsy. The ability to use CM to image in real time without discomfort to the patient makes it a powerful tool to assist in the diagnosis of skin disease.


Structure-activity relationship in a new series of atropine analogues. 1. N,N'-Disubstituted 6,7-diazabicyclo[3.2.2]nonane derivatives.
The synthesis of a new series of N,N'-disubstituted 6,7-diazabicyclo[3.2.2]nonane derivatives is described. The antimuscarinic potency of these drugs was evaluated in the guinea pig ileum and compared to that of atropine sulfate. All the drugs tested competitively inhibited the acetylcholine-induced contractions. Kd values were calculated and, in several cases, compared to those obtained by direct binding to the muscarinic receptor from mouse brain. The order of potencies followed that which is known for various tropine and pseudotropine esters; that is, the 3alpha configuration is more potent than the 3beta configuration, and the quaternary analogues are more potent than the tertiary ones. The antimuscarinic activity of the drugs is dicussed in terms of their acetylcholine-like molecular arrangement that gives rise to a characteristic interaction pharmacophore.


Sequence of eruption of permanent teeth and epiphyseal union in three species of African monkeys.
Sequences of eruption of teeth and union of epiphyses determined for three species of African Cercopithecinae. These sequences are highly scalable and are highly comparable between among the species. Some sex differences in sequence were found within each species. The sequences of epiphyseal union in these species of Old World monkeys are very similar to published sequences in New World monkeys and other groups of higher primates. It appears that there is a single pattern common to the Anthropoidea as a whole.


[Standard methods of blood group serology--state and trends of development].
The notion of transfusion serology comprises also serologic examinations in connection with transfusions of thrombocytes and leucocytes. The minimum demands of serological methods in the German Pharmacopoeia 7 (DAB 7) obligatory nowadays before transfusions of full blood and concentrates of erythrocytes should be changed and enlarged as follows: Obligatory carrying-through of the bed-side-test, inclusion of the ferment- and/or Coombs-test as major test into the cross typing, abolition of the minor test. In connection with the transfusions of leucocytes and thrombocytes determinations of the HLA-antibodies and cross typings are practicable in the institutions of the transfusion service. Transfusion must principally be striven for, taking into consideration the HLA-typing, but at present it is only limitedly possible. The search for donors among relations by blood increases the chances of the serological compatibility. Necessity and scale of an "emergency serology" still need discussion. Optimum haemotherapy is possible only then, when clinics and transfusion service work together in very close coordination.


Herpes Zoster Induced Osteomyelitis in the Immunocompromised Patients: A 10-year Multicenter Study.
Alveolar bone necrosis induced by Herpes zoster infection is considered as a rare manifestation of osteomyelitis and few case reports are presented in the literature. The aim of this study was to evaluate mandibular osteomyelitis caused by herpes zoster in the immunocompromised patients with histopathologically documented osteomyelitis in the mandible and herpes zoster infection. 30 patients were recruited in this cross-sectional study. 19 patients were completely edentulous, 4 patients were partially edentulous and 7 with complete dentition. In all cases, specimens were analyzed using a conventional polymerase chain reaction (PCR) test for varicella zoster virus. 16 patients underwent dialysis, 9 patients received chemotherapy treatments and 5 patients had transplantation (four kidneys and one liver). Histopathological assessment demonstrated a nonspecific bone necrosis exhibiting an eosinophilic, homogeneous non-vital bone tissue with peripheral resorption surrounded by reactive connective tissue. PCR test was positive in 21 cases. This study demonstrated that the frequency of osteomyelitis induced by herpes zoster could be more than the records provided by previous studies. Histopathological findings might be nonspecific in such patients. PCR test was not positive for all HZ induced osteomyelitis patients.


Overexpression of Lox in triple-negative breast cancer.
Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancers. It is associated with a poor prognosis and typically earlier onset of metastasis in comparison with other breast cancer subtypes. Since TNBC lacks the expression of estrogen and progesterone receptors and Her2 status is also negative, there is currently no target that can be used for systemic therapy. Epithelial-mesenchymal transition (EMT) plays an important role in tumor progression and metastasis. In this study, we examined a subset of EMT markers consisting of Snail, Twist-1 and Lox in TNBC and non-TNBC breast cancer subtypes and analyzed their expression pattern in regard to subtype, clinico-pathological parameters and prognosis. We analyzed 659 breast cancer samples from two tissue microarrays. Breast cancer samples were categorized into two groups according to hormone receptor expression and Her2 status (n = 146 were triple negative, n = 513 were non triple-negative). Immunohistochemical expression of Snail, Twist-1 and Lox was semi-quantitatively analyzed using a three-tiered (weak-moderate-strong) scoring system. Results were statistically analyzed and correlated to clinico-pathological parameters and overall survival. Strong overexpression of Lox was significantly higher in triple negative breast cancers when compared to non triple-negative breast cancers (p < 0.001). No difference was seen between the groups regarding Snail and Twist expression (p > 0.05). In addition, Lox expression was significantly stronger in poorly differentiated (G3) breast cancers (p < 0.001 for Lox). The EMT marker Lox has a differential expression pattern in breast cancer, being significantly overexpressed in triple negative breast cancers. We could not link this expression to prognosis, however, this marker might be explored in future studies as possible target for systemic therapy of TNBC.


Minimum Clearance Distance in Fall Arrest Systems with Energy Absorber Lanyards.
Accidents due to falls from height are one of the main causes of death in workplaces. Fall arrest systems (FAS) are designed to arrest the fall safely without injuring the accident victim. Their main mission is to restrain the body so as to prevent it from hitting the ground, generating forces and accelerations in the arrest process that are not harmful. A lack of empirical evidence and scant technical information provided by manufacturers regarding minimum clearance distance (MCD) below anchorage makes it necessary to study the safety distances required in the use of Energy Absorber Lanyards (EAL). This paper aims to determine the MCD below anchorage to arrest a fall using an EAL without hitting the ground. The real deformation of EAL when stopping a fall is studied. Ten EAL models distributed internationally by six manufacturers were chosen. Dynamic behavior tests were performed on the samples. Using image processing the total elongation of the equipment (elastic plus plastic) is obtained. The main conclusions are that maximum plastic elongation could be reduced by 29%. The method described in EN 355: 2002 underestimates elongation by up to 70% for some equipment 20% of EAL's exceed the maximum arrest force (Fm) allowed in EN 355. The MCD data provided by manufacturers is not reliable. The data provided by manufacturers are incomplete. It is recommended that quality control for EAL's be strengthened to ensure that products launched onto the market meet the requirement of EN355. The findings of this study recommended increasing MCD distance longer than that calculated according to EN355, at less than 1 m.


Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice.
Obesity and insulin resistance represent a problem of utmost clinical significance worldwide. Insulin-resistant states are characterized by the inability of insulin to induce proper signal transduction leading to defective glucose uptake in skeletal muscle tissue and impaired insulin-induced vasodilation. In various pathophysiological models, melatonin interacts with crucial molecules of the insulin signaling pathway, but its effects on glucose homeostasis are not known. In a diet-induced mouse model of insulin resistance and normal chow-fed control mice, we sought to assess the effects of an 8-wk oral treatment with melatonin on insulin and glucose tolerance and to understand underlying mechanisms. In high-fat diet-fed mice, but not in normal chow-fed control mice, melatonin significantly improved insulin sensitivity and glucose tolerance, as evidenced by a higher rate of glucose infusion to maintain euglycemia during hyperinsulinemic clamp studies and an attenuated hyperglycemic response to an ip glucose challenge. Regarding underlying mechanisms, we found that melatonin restored insulin-induced vasodilation to skeletal muscle, a major site of glucose utilization. This was due, at least in part, to the improvement of insulin signal transduction in the vasculature, as evidenced by increased insulin-induced phosphorylation of Akt and endoethelial nitric oxide synthase in aortas harvested from melatonin-treated high-fat diet-fed mice. In contrast, melatonin had no effect on the ability of insulin to promote glucose uptake in skeletal muscle tissue in vitro. These data demonstrate for the first time that in a diet-induced rodent model of insulin resistance, melatonin improves glucose homeostasis by restoring the vascular action of insulin.


The effects of fish oil on triglycerides, cholesterol, fibrinogen and malondialdehyde in humans supplemented with vitamin E.
The effects of fish oils supplemented with 0.3 IU/g and 1.5 IU/g of vitamin E were compared in a double-blind, cross-over study. Twelve healthy volunteers were given 30 mL/day of either oil for 3 wk. Intake of the vitamin E-rich fish oil resulted in a marked decrease in serum triglycerides (48%) and in fibrinogen (11%). After administration of the low vitamin E-containing oil there was a considerably smaller reduction of serum triglycerides and no significant reduction of fibrinogen. Both oils caused an increase in high density lipoprotein cholesterol and a decrease in the atherogenic index, but neither oil altered the total cholesterol level. Serum vitamin E was decreased by 9% and plasma malondialdehyde was increased by 122% after intake of the low vitamin E-containing oil, but both remained normal after intake of the other oil. The effect of vitamin E may be due to inhibition of fatty acid peroxidation with less formation of malondialdehyde and a larger amount of active (n-3) fatty acids in their sites of action in the liver, resulting in a greater decrease in the synthesis of triglycerides and fibrinogen.


Mechanisms and consequences of neuronal stretch injury in vitro differ with the model of trauma.
The deformation to the brain that occurs during traumatic brain injury (TBI) results in a complex strain distribution throughout the brain tissue. Recently, many in vitro models of neuronal injury have been developed to simplify the mechanics which occur during TBI. We hypothesized that the type of mechanical insult imparted onto neurons would significantly alter both the mechanism and severity of the neuronal response to injury. In this study, primary cortical neurons were cultured on an elastic substrate and subjected to graded levels (0%, 10%, 30%, 50%) of either uniaxial (cells stretched in one direction only) or biaxial (cells simultaneously stretched in two directions) stretch. We found that neurons stretched in either injury paradigm exhibited immediate increases in intracellular free calcium ([Ca2+]i), but the magnitude of the ([Ca2+]i) rise was nearly an order of magnitude higher in biaxially stretched neurons compared to uniaxially stretched neurons. Moreover, while the ([Ca2+]i) transient after uniaxial stretch was blocked with specific channel antagonists (APV, CNQX, nimodipine, TTX), a substantial ([Ca2+]i) transient persisted in biaxially stretched neurons. We theorized that the additional calcium influx after biaxial stretch entered through nonspecific pores/tears formed in the membrane, since biaxially stretched neurons exhibited significant uptake of carboxyfluorescein, a molecule typically impermeant to cell membranes. Despite the large ([Ca2+]i) transients, neither injury profile resulted in death within 24 h of injury. Interestingly, though, uniaxially stretched neurons exhibited enhanced [Ca+2]i influx following NMDA stimulation 24 h after trauma, compared to both control and biaxially stretched neurons. These data point out that the type of mechanical insult will influence the acute mechanisms of injury in vitro, can cause differences in the response to potential secondary excitotoxic injury mechanisms, and emphasizes the need to further study how these mechanical conditions can separately affect cell fate following mechanical injury.


[Clinical study of yishen jianpi yangxue tongli therapy in treating polycystic ovary syndrome].
To observe the effect of Yishen Jianpi Yangxue Tongli Therapy (YJYTT) in treating polycystic ovary syndrome (PCOS) and to explore the therapeutic mechanism of YJYTT. One hundred and seven PCOS patients with syndrome differentiation of TCM as Pi-Shen Yang deficiency were randomly divided into two groups, the treated group (n = 76) was treated with Chinese herbal medicine, while the control group (n = 31) was treated by clomiphen. The therapeutic effect in both groups and the change of body mass index (BMI), Ferriman-Gallway (F-G) score, serum sex hormones and serum oral glucose tolerance test (OGTT) before and after treatment were observed. The comparison of total effective rate between two groups was insignificantly different, but the pregnancy rate of the treated group (65.7%) was markedly higher than that of control group (25.0%, P < 0.01). Also, significant difference was shown in the aspect of BMI, F-G score, serum testosterone (T), luteinizing hormone (LH) and OGTT, etc. between the two groups (P < 0.05). The YJYTT could markedly improve the clinical symptoms and pregnancy rate of PCOS patients, particularly showing good effect to the clomiphen resistant patients. The mechanism possibly was due to its regulation on hypothalamus-pituitary-ovarium axis and reducing the insulin resistance.


Prevalence of overweight in Moroccan patients with rheumatoid arthritis and its relationships with disease features.
We aimed to estimate the prevalence of overweight in Moroccan patients with rheumatoid arthritis (RA) and its relationships with disease activity, functional disability, structural damage, and immunological status. Two hundred fifty patients with RA were consecutively included. Patients' characteristics were specified. The following data were collected: age, disease duration, disease activity (evaluated with physical examination data, biological tests (erythrocyte sedimentation rate and C-reactive protein), and the disease activity score (DAS28)), radiographic changes (assessed by the Sharp's method), functional disability (assessed by using the Health Assessment Questionnaire), extra-articular manifestations, immunological status, and treatment details. Overweight was defined according to the body mass index (BMI) values: underweight, <18.5; normal weight, 18.5-24.9; overweight, 25-29.9; and obesity, ≥30. The mean age of patients was 46.31 ± 12.64 years. The mean disease duration was 9.46 ± 8.43 years. Seventy-five patients (30%) were overweight, 42 (16.8%) were obese, and 133 (53.2%) were normal. Increased BMI was associated with the activity of disease (DAS28) (r = 0.426), structural damage (Sharp total score) (r = 0.297), the rate of rheumatoid factor (r = 0.311), and with the rate of anti-cyclic citrullinated protein antibodies (for all p ≤ 0.01). There were no statistically significant differences in BMI according to gender, dose and duration of corticosteroids, or functional impairment. In our sample, overweight seems to be prevalent in our RA patients. Overweight seems to occur independently of treatment and shown to be mainly associated to disease activity, structural damage, and immunological status. Large studies are needed to confirm those results.


Systematic screening for mutations in the human N-methyl-D-aspartate receptor 1 gene in schizophrenic patients from the German population.
Evidence for a dysfunction of the N-methyl-D-aspartate (NMDA) type of ionotropic glutamate receptors in schizophrenic patients, comes from neurochemical and clinical pharmacologic data. Therefore, the NMDAR1 gene can be regarded as an interesting candidate gene for schizophrenia. Several groups have tried to identify variants of this gene in schizophrenic patients in different, however not in German, populations. We sought to identify sequence changes of potential functional relevance in genomic DNA from 46 German unrelated schizophrenic patients by means of single-strand conformation analysis. No mutations of likely functional relevance were observed. We identified two synonymous coding Single Nucleotide Polymorphisms (cSNPs) in exons 6 and 7, and two SNPs in exon-flanking intronic sequences. Genotype distribution of these four SNPs was not significantly different between schizophrenic patients and controls. Our results suggest that the NMDAR1 subunit is not frequently involved in the development of schizophrenia in the German population.


[A Case of Malignant Peripheral Nerve Sheath Tumor of the Anus Resected by Robot Assisted-APR].
An 81-year-old female visited a local hospital with complaints of anal pain. A tumor was found on the right side of her anus, and the histopathological diagnosis was a non-epithelial malignant tumor. Therefore, the patient was referred to our hospital. Result of imaging inspection revealed that the tumor had invaded the lower rectum, but had not distantly metastasized. Based on the findings of another biopsy, the patient was diagnosed with a malignant peripheral nerve sheath tumor (MPNST). Robot-assisted abdominoperineal resection(D1)was performed, and the lesion was resected without any pathological remnants. During the postoperative period, the patient developed perineal wound infection. Subsequently, the patient was discharged from the hospital on postoperative day 10. At the 6-month postoperative follow-up, no recurrence was noted. Most MPNSTs occur in the limbs, trunk, and neck. MPNST in the primary gastrointestinal tract or in the vicinity of the gastrointestinal tract is relatively rare, and in principle, combined resection of the intestinal tract is required for surgical treatment. Here, we report a case of MPNST that occurred near the anus and infiltrated to the lower rectum and was completely resected by robot-assisted abdominoperineal resection.


Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population.
Recent evidence suggests that the opioid system is implicated in the pathophysiology of alcohol use disorder (AUD). We aimed to examine the genetic influence of opioid receptors on susceptibility to AUD and its clinical and psychological characteristics including harmful drinking behavior and various aspects of impulsivity in AUD patients. Three μ-opioid receptor gene (OPRM1) variants and two κ-opioid receptor gene (OPRK1) variants were examined in 314 male patients with AUD and 324 male controls. We applied the Alcohol Use Disorders Identification Test (AUDIT), Obsessive Compulsive Drinking Scale (OCDS), and Alcohol Dependence Scale. AUD patients also completed the stop-signal task, delay discounting task, balloon analogue risk task, and the Barratt Impulsiveness Scale version 11 (BIS-11). No significant differences in genotype distributions or haplotype frequencies were found between AUD patients and controls. However, OPRK1 SNP rs6473797 was significantly related to the severity of alcohol-related symptoms as measured by AUDIT and OCDS and a haplotype containing rs6473797 was also related to OCDS scores in AUD patients. For other psychological traits, OPRM1 SNP rs495491 was significantly associated with scores on the motor subfactor of the BIS-11. Genetic variations in opioid receptors may contribute to symptom severity and impulsivity in AUD patients.


Gastroesophageal Reflux Treatment in Infancy Through Young Adulthood.
Gastroesophageal reflux treatment varies greatly across the pediatric age spectrum. Infant reflux treatments rely heavily on nutritional interventions, whereas reflux in older children is treated more commonly with medications. However, because of the broad differential diagnosis, treatment nonresponse merits a re-evaluation of the diagnosis being treated and additional testing to provide a more precision-medicine approach to care.


Human corneal epithelial cells require MMP-1 for HGF-mediated migration on collagen I.
To investigate the potential regulation of matrix metalloproteinases (MMPs) by hepatocyte growth factor (HGF), and to identify individual MMPs essential for migration of human corneal epithelial cells. Migration of human corneal epithelial cells (HCECs) was measured with a colony dispersion assay in response to concentrations of HGF (0-50 ng/mL). MMP activity in the conditioned media collected from the dispersion assay was assessed by zymography. The broad-spectrum MMP inhibitor ilomastat (1-100 microM) or an MMP-9-neutralizing antibody (1-10 microg/mL) were included in the dispersion assay to determine their effects on HCEC migration. Immunocytochemistry and in situ hybridization were used to localize MMP-1 in HCECs in the colony dispersion assay and in a human ex vivo corneal wound-healing model, respectively. ELISA for MMP-1 was performed on conditioned medium from migrating HCECs. Neutralizing antibodies to MMP-1 and -9 were added to an in vitro scratch-wound model to assess the effect on HCEC healing. HCEC migration (P < 0.05) and MMP-2 and -9 released into the medium increased in response to HGF in a dose-dependent manner up to 20 ng/mL. Broad-spectrum MMP inhibition significantly reduced HCEC migration (P < 0.05). In contrast, neutralization of MMP-9 increased migration (P < 0.05). MMP-1 was found in association with HCECs at the migratory leading edge in both the dispersion and the ex vivo wound-healing experiments, and was found to be stimulated above basal levels by HGF. Neutralization of MMP-1 significantly decreased (P < 0.05), whereas neutralization of MMP-9 significantly increased (P < 0.05), scratch-wound closure. This study provided novel data regarding HCEC migration in response to HGF and highlighted the importance of MMPs, particularly MMP-1 in migration and possibly reepithelialization in vivo. MMP-9 and/or -2 may be released by HCECs to remodel matrix behind the leading migratory front. Studies such as this are essential to assist in the safe and efficacious design of MMP inhibitors for therapeutic use in the eye.


Computed tomography of calcified gastric carcinoma.
The CT findings in a case of calcified gastric carcinoma of the mucin-producing type are described. These findings include localized thickening of the gastric wall and multiple tiny calcific nodules within it.


[Imaging of intraocular and orbital vessels using angiodynography].
Color Doppler imaging (CDI) is a recent advance in ultrasonography. It allows simultaneous two-dimensional structural imaging and evaluation of blood-flow characteristics. The velocity information of the scan is extracted and added to the images as color information. A total of 20 normal eyes and 30 patients with intraocular tumors were examined with this technique. The central retinal artery, the posterior cliliary arteries, the opthalmic artery and the central retinal vein could be located in all patients. In the intraocular tumors blood flow was detected reliably. Spectrum analysis of the displayed vessels allows semiquantitative assessment of blood flow in these vessels. This new technique of color Doppler imaging offers a new modality to study ocular and orbital blood flow.


Effectiveness research in marriage and family therapy: introduction.
The papers in this volume offer compelling evidence that MFT is making significant progress toward becoming an evidenced based discipline. Nonetheless, a large gap persists between research and practice, which perpetuates a false dichotomy between the art and science of treatment and has other deleterious consequences for the field. The methodological strengths of the investigations reported, which focus on clinical trials, are discussed along with concerns raised about this type of research. Several important challenges facing MFT research in the decades ahead are described. Finally, MFT education must be changed substantially to give more emphasis to the science of the discipline.


Cross-Coupling Reaction of Alkenyl Sulfoximines and Alkenyl Aminosulfoxonium Salts with Organozincs by Dual Nickel Catalysis and Lewis Acid Promotion.
In this article, the cross-coupling reaction (CCR) of exocyclic, axially chiral, and acyclic alkenyl (N-methyl)sulfoximines with alkyl- and arylzincs is described. The CCR generally requires dual Ni catalysis and MgBr2 promotion, which is effective in diethyl ether but not in THF. NMR spectroscopy revealed a complexation of alkenyl sulfoximines by MgBr2 in diethyl ether, which suggests an acceleration of the oxidative addition through nucleofugal activation. The CCR of alkenyl sulfoximines generally proceeds in the presence of Ni(dppp)Cl2 as a precatalyst and MgBr2 with alkyl- and arylzincs with a high degree of stereoretention at the C and the S atom. CCR of axially chiral alkenyl sulfoximines with Ni(PPh3 )2 Cl2 as a precatalyst and ZnPh2 does not require salt promotion and is stereoretentive. The reaction with Zn(CH2 SiMe3 )2 , however, demands salt promotion and is not stereoretentive. CCR of axially chiral α-methylated alkenyl sulfoximines afforded persubstituted axially chiral alkenes with high selectivity. Alkenyl (N-triflyl)sulfoximines engage in a stereoretentive CCR with Grignard reagents and Ni(PPh3 )2 Cl2 . Ni-Catalyzed and MgBr2 -promoted CCR of E-configured acyclic alkenyl sulfoximines and aminosulfoxonium salts with ZnPh2 and Zn(CH2 SiMe3 )2 is stereoretentive with Ni(dppp)Cl2 and Ni(PPh3 )2 Cl2 . CCRs of acyclic alkenyl sulfoximines and alkenyl aminosulfoxonium salts, carrying a methyl group at the α position, take a different course and give alkenyl sulfinamides under stereoretention at the S and C atom. CCR of acyclic, exocyclic, and axially chiral alkenyl sulfoximines has been successfully applied to the stereoselective synthesis of homoallylic alcohols, exocyclic alkenes, and axially chiral alkenes, respectively.


Nephrin is an important component of the barrier system in the testis.
Nephrin, a gene product of the congenital nephrotic syndrome of the Finnish type (NPHS1), is a 1242-residue putative transmembrane protein of the immunoglobulin family of cell adhesion molecules. The expression of this gene is localized in rat and human glomerular epithelial cells. Here we report the expression of nephrin in various tissues other than the kidneys in mice. The expression of nephrin mRNA in various tissues of mice, including the kidneys, testes, spleen, thymus and brain, were first investigated by the RT-PCR method, and it was shown that a high level of nephrin mRNA could be detected in the testes of mice 1-6 weeks old. In situ hybridization revealed the expression of the nephrin gene in the Sertoli cells. Additionally, immunofluorescent staining studies indicated that nephrin was colocalized with anchoring protein ZO-1 in the mouse testis. From these results, it is inferred that nephrin is an important component of the barrier system in testes.


An Evaluation of Patient Risk Factors to Determine Eligibility to Undergo Orthopaedic Surgery in a Freestanding Ambulatory Center A Survey of 4,242 Consecutive Patients.
The value proposition of surgery at freestanding ambulatory surgery centers (FSASCs) in terms of efficiency, safety, and patient satisfaction is well established and has led to increased FSASC utilization. However, there are comorbid conditions that disqualify certain patients from surgery at FSASCs. Understanding the percentage of patients whose comorbid conditions exclude them from FSASCs is important for the proper planning and utilization of operating room assets. We aim to understand the percentage of excluded patients, and we predict that certain procedures have higher rates of disqualification due to the types of patients who undergo them. We reviewed the records of 4,242 consecutive patients undergoing outpatient orthopaedic surgeries in our hospital system from July 2015 to February 2016. Patient characteristics, comorbidities, and procedures performed were included in our database. We analyzed each case and determined eligibility for surgery at our FSASC based on established comorbidity exclusionary guidelines. Chi-square and t-tests were used to establish statistical significance. Of 4,242 patients, 878 (20.7%) were ineligible for surgery at our FSASC based on accepted exclusionary guidelines. The average body mass index (BMI) of FSASC-eligible patients was 27.37, compared to 31.68 for FSASC-ineligible patients (p < 0.001). The majority, 85.6% (543/634), of American Society of Anesthesiologists (ASA) class 3 patients were FSASC-ineligible. The most common reasons for excluding patients from surgery at our FSASC were morbid obesity (25.4% of ineligible cases), untreated obstructive sleep apnea (22.1%), age less than 13 (19.6%), and coronary artery disease with prior intervention (13.3%). When stratifying by procedure, the operations most likely to be FSASC-ineligible were contracture releases (39.13% ineligible, p = 0.03), trigger finger releases (36.14%, p < 0.001), carpal tunnel releases (30.63%, p = 0.009), tumor resections (38.89%, p = 0.056), rotator cuff repairs (25.47%, p = 0.078), and subacromial decompressions (30.23%, p = 0.12), primarily because these patients have more comorbidity (ASA 2.20 vs. 1.88, p < 0.001). Roughly 1 in 5 patients is ineligible for surgery at a freestanding ASC due to disqualifying comorbidities. Although FSASCs offer cost effective care that satisfies patients, we must understand that certain patients cannot have their surgeries at these venues. In addition, we must use additional caution when scheduling certain procedures at a FSASC. Therefore, as the number and complexity of the surgeries performed at FSASCs increase, we must better understand the factors that make patients better candidates for surgery in a hospital setting, thus minimizing transfers and readmissions and maximizing the value proposition of FSASCs.


Influence of Metal Coordination on the Gas-Phase Chemistry of the Positional Isomers of Fluorobenzoate Complexes.
The fragmentation behaviors of the o-, m-, and p-fluorobenzoate complexes of La3+, Ce3+, Fe3+, Cu2+, and UO22+ were investigated by electrospray ionization mass spectrometry, and the corresponding reaction mechanisms were explored by density functional theory (DFT) calculations. Fluoride transfer product LaIIIFCl3-/CeIIIFCl3- and decarboxylation product LaIIICl3(C6H4F)-/CeIIICl3(C6H4F)- were observed when the carboxylate precursors LaIIICl3(C6H4FCO2)-/CeIIICl3(C6H4FCO2)- were subjected to collision-induced dissociation. The variation in product ratios, which is not obvious in the meta and para cases, qualitatively follows the increasing overall energy barrier and reaction endothermicity of the two-step CO2/C6H4 elimination mechanism, and this aligns with the increase in U-F distance in the ortho, meta, and para decarboxylation product isomers. In contrast, the mass spectra of FeIIICl3(C6H4FCO2)-/CuIICl2(C6H4FCO2)- are dominated by the reduction product FeCl3-/CuCl2- regardless of the fluorobenzoate isomer. DFT/B3LYP calculations show that the two-step CO2/C6H4F elimination pathways are comparable in energy for all three positional isomers. It is energetically more favorable to give the reduction product than the fluoride transfer product, which is opposite to the lanthanum cases. Although the decarboxylation product was observed for all three UVIO2Cl2(C6H4FCO2)- isomers, the ortho isomer behaves more similarly to LaIIICl3(C6H4FCO2)-/CeIIICl3(C6H4FCO2)- as evidenced by the formation of UVIO2FCl2-, and the appearance of UVO2Cl2- in the cases of the meta and para isomers indicates the similarity with FeIIICl3(C6H4FCO2)-/CuIICl2(C6H4FCO2)-. The shorter U-F distance in UVIO2Cl2(o-C6H4F)- causes the decrease in the fluoride transfer barrier and thus makes this process more favorable over o-C6H4F radical loss to give UVO2Cl2-.


Partitioning and Spatial Distribution of Drugs in Ocular Surface Tissues.
Ocular drug absorption after eye drop instillation has been widely studied, but partitioning phenomena and spatial drug distribution are poorly understood. We investigated partitioning of seven beta-blocking drugs in corneal epithelium, corneal stroma, including endothelium and conjunctiva, using isolated porcine tissues and cultured human corneal epithelial cells. The chosen beta-blocking drugs had a wide range (-1.76-0.79) of n-octanol/buffer solution distribution coefficients at pH 7.4 (Log D7.4). In addition, the ocular surface distribution of three beta-blocking drugs was determined by matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) after their simultaneous application in an eye drop to the rabbits in vivo. Studies with isolated porcine corneas revealed that the distribution coefficient (Kp) between the corneal epithelium and donor solution showed a positive relationship and good correlation with Log D7.4 and about a 50-fold range of Kp values (0.1-5). On the contrary, Kp between corneal stroma and epithelium showed an inverse (negative) relationship and correlation with Log D7.4 based on a seven-fold range of Kp values. In vitro corneal cell uptake showed a high correlation with the ex vivo corneal epithelium/donor Kp values. Partitioning of the drugs into the porcine conjunctiva also showed a positive relationship with lipophilicity, but the range of Kp values was less than with the corneal epithelium. MALDI-IMS allowed simultaneous detection of three compounds in the cornea, showed data in line with other experiments, and revealed uneven spatial drug distribution in the cornea. Our data indicate the importance of lipophilicity in defining the corneal pharmacokinetics and the Kp values are a useful building block in the kinetic simulation models for topical ocular drug administration.


Conformational changes of trialanine induced by direct interactions between alanine residues and alcohols in binary mixtures of water with glycerol and ethanol.
Despite the increasing relevance of characterizing local conformational distributions in the unfolded state, an unambiguous description of the role that solvation and the addition of certain cosolvents play in altering this ensemble has yet to emerge. Alcohol cosolvents, and specifically glycerol, are known to act as protein stabilizers. The underlying mechanism of this effect is, however, still debated. Short alanine-based peptides provide a suitable model system for exploring the influence of cosolvents on backbone conformations, as ample experimental evidence now indicates that alanine does not exhibit a true statistical coil behavior but rather shows strong preference for sampling the polyproline II (PPII) region of the Ramachadran map when solvated in water. To explore the effect glycerol and ethanol cosolvents have on the conformational distribution of trialanine, we combined UV-CD and H NMR spectroscopies. The temperature dependence of the conformationally sensitive maximum dichroism (Δε) and (3)J(H(α)H(N)) coupling constants of two amide protons (N- and C-terminal) was subjected to a global thermodynamic analysis based on simple two-state PPII↔β models. Interestingly, our results show that even small admixtures of alcohol (5% v/v) considerably change the spectral parameters, Δε(PPII) and Δε(β), as well as the enthalpic and entropic differences between the two states. For the central residue of trialanine in 5% glycerol, we obtained a gain in enthalpy favoring PPII of ΔΔH(n) = -4.80 kJ/mol and a compensating increase in entropy favoring the β-strand of ΔΔS(n) = -13.53[J/mol K]. This causes increases in -ΔG and slight increases in PPII content. Further addition of alcohol, however, reverses the trend in that it causes a destabilization of the hydration shell and a shift toward β-strand conformations. The combined manifold of ΔH and ΔS values obtained for the investigated binary mixtures and the pure aqueous solvent exhibits an excellent linear correlation, which reflects enthalpy-entropy compensation and a common transition temperature. The latter can be considered an indication of a weak binding between cosolvent and peptide. A comparison of infrared and Raman spectra of trialanine in water and in water-alcohol mixtures indeed reveals a close proximity between aliphatic side chains of alanine residues and alcohol molecules even for 5% (v/v) alcohol-water mixtures. Hence, our results provide the first experimental evidence for direct interactions between, e.g., glycerol and peptides in aqueous solutions, in line with the result of recent calculations by Vagenende et al. (Biochemistry 2009, 48, 11084-11096) but at variance with preferential exclusion theories.


Principles and Practical Considerations for the Analysis of Disease-Associated Alternative Splicing Events Using the Gateway Cloning-Based Minigene Vectors pDESTsplice and pSpliceExpress.
Splicing is an important RNA processing step. Genetic variations can alter the splicing process and thereby contribute to the development of various diseases. Alterations of the splicing pattern can be examined by gene expression analyses, by computational tools for predicting the effects of genetic variants on splicing, and by splicing reporter minigene assays for studying alternative splicing events under defined conditions. The minigene assay is based on transient transfection of cells with a vector containing a genomic region of interest cloned between two constitutive exons. Cloning can be accomplished by the use of restriction enzymes or by site-specific recombination using Gateway cloning. The vectors pDESTsplice and pSpliceExpress represent two minigene systems based on Gateway cloning, which are available through the Addgene plasmid repository. In this review, we describe the features of these two splicing reporter minigene systems. Moreover, we provide an overview of studies in which determinants of alternative splicing were investigated by using pDESTsplice or pSpliceExpress. The studies were reviewed with regard to the investigated splicing regulatory events and the experimental strategy to construct and perform a splicing reporter minigene assay. We further elaborate on how analyses on the regulation of RNA splicing offer promising prospects for gaining important insights into disease mechanisms.


Early life handling decreases serotonin turnover in the nucleus accumbens and affects feeding behavior of adult rats.
In our previous studies, we reported that neonatally handled rats have an increased ingestion of sweet food but are resistant to the damaging effects of a chronic exposure to a highly palatable diet. Accumbal serotonin (5-HT) is important for feeding behavior and plays a role in the vulnerability to diet-induced obesity. Therefore, our hypotheses were (1) 5-HT turnover in the nucleus accumbens is altered in neonatally handled animals and plays a role in their differential feeding behavior and (2) if this is so, a chronic pharmacological treatment affecting 5-HT reuptake (chronic imipramine) would be able to revert the behavioral findings. Litters were divided into nonhandled and handled (10 min/day, Days 1-10 after birth). In Experiment 1, we demonstrated that a decreased 5-HT metabolism in the nucleus accumbens was observed in adult handled animals. In Experiment 2, the two previous groups were subdivided and assigned to receive imipramine diluted in water or water alone. After 30 days of treatment, we evaluated their weight gain and feeding behavior. Handled rats weighed less than nonhandled rats, and all imipramine-treated rats showed a reduction in weight gain after 60 days of treatment. Imipramine reverted the increased sweet food consumption seen in neonatally handled rats. We conclude that serotonin is involved in the altered feeding behavior of neonatally handled rats, and this protocol is an important tool for studying the mechanisms by which early life events have a long-term impact on feeding preferences.


Linking differences in action perception with differences in action execution.
Successful human social interactions depend upon the transmission of verbal and non-verbal signals from one individual to another. Non-verbal social communication is realized through our ability to read and understand information present in other people's actions. It has been proposed that employing the same motor programs, we use to execute an action when observing the same action underlies this action understanding. The main prediction of this framework is that action perception should be strongly correlated with parameters of action execution. Here, we demonstrate that subjects' sensitivity to observed movement speeds is dependent upon how quickly they themselves executed the observed action. This result is consistent with the motor theory of social cognition and suggests that failures in non-verbal social interactions between individuals may in part result from differences in how those individuals move.


An ATP-dependent supercoiling topoisomerase of Chlamydomonas reinhardtii affects accumulation of specific chloroplast transcripts.
We have found that Chlamydomonas reinhardtii cells contain an ATP-dependent topoisomerase activity that supercoils circular DNA in vitro. Subsequent addition of a type I topoisomerase eliminates the supercoils. Like bacterial gyrase, this activity is inhibited by low concentrations of novobiocin (less than 0.1 microM) and by nalidixic acid (less than 0.1 microM). We have examined the effects of these topoisomerase inhibitors on accumulation of various chloroplast transcripts in vivo. Novobiocin differentially affected such transcripts; some transcripts became more abundant while many others were reduced in the presence of this drug. Nalidixic acid on the other hand caused many transcripts to become more abundant albeit to varying degrees. Inhibitors of this algal topoisomerase specifically stimulate a family of related transcripts which we have previously shown to be under light-dark control. We discuss how the inhibitors of this topoisomerase might exert their in vivo effects.


PEG10 plays a crucial role in human lung cancer proliferation, progression, prognosis and metastasis.
Paternally expressed gene 10 (PEG10) has been identified as a genetic imprinted gene, which is important for apoptosis resistance in cancer cells. Mounting evidence suggests that PEG10 is expressed in the majority of hepatocellular carcinoma (HCC) cells with growth-promoting activity. In the present study, we evaluated the correlation between PEG10 expression and the clinicopathological features of lung, breast and HCC tumors, and predicted the relationship between survival and expression levels of PEG10 in lung cancer patients. Furthermore, we chose non-small cell lung cancer cell line A549 as a model to analyze the function of PEG10 in proliferation and metastasis in vitro. Our results revealed that expression of PEG10 was closely correlated with clinical TNM grade and patient prognosis in lung cancer. PEG10 enhanced cell proliferation and promoted tumor cell migration and invasion by upregulating the expression of β-catenin, MMP-2 and MMP-9, and decreased the expression of E-cadherin in the A549 cells. Our findings provide significant insight into the molecular mechanisms of lung cancer and offer novel ideas for designing new therapeutic targets for lung carcinoma.


Compound Kushen injection attenuates angiotensin II‑mediated heart failure by inhibiting the PI3K/Akt pathway.
Compound Kushen injection (CKI) is a type of traditional Chinese medicine that has previously been studied for the treatment of various types of cancer. Previous studies have reported that CKI regulates cell apoptosis by downregulating the PI3K/Akt pathway. The present study aimed to determine whether CKI alleviates heart failure (HF) by attenuating cardiomyocyte apoptosis via the inhibition of the PI3K/Akt pathway. Angiotensin II (Ang II) was used to elicit HF, and osmotic minipumps with either Ang II (2 µg/kg/day) or phosphate‑buffered saline (PBS; 200 µl) were subcutaneously implanted into 6‑week‑old male C57BL/6 mice for 3 weeks. In addition, PBS or CKI (25 mg/kg/day) were subcutaneously infused once a day for 3 weeks. Echocardiography was used to examine hemodynamics. The myocardial injury biomarkers, cardiac troponin I and N‑terminal (NT)‑pro hormone B‑type natriuretic peptide, were assessed using enzyme‑linked immunosorbent assay. Transmission electron microscopy was used to determine the morphology of the myocardium. The rate of apoptosis was detected using TUNEL staining and flow cytometry (FCM), and the expression levels of apoptosis‑related proteins were measured using western blot (WB) analysis. Moreover, H9C2 cells were treated with CKI (2 mg/ml) or LY294002 (an inhibitor of the PI3K/Akt pathway; 25 µmol/l) in combination with Ang II (1 µmol/l) for 48 h. Cell Counting Kit‑8 assay, FCM and WB analysis were performed in the H9C2 cells to examine cell viability, cell cycle distribution and representative signaling proteins. It was found that CKI promoted healthy cardiac function, reduced myocardial structural damage and reduced the rate of cardiomyocyte apoptosis. CKI markedly attenuated the expression of apoptosis‑related proteins in the PI3K/Akt pathway. The results of the in vitro experiments indicated that CKI promoted cardiomyocyte proliferation and inhibited apoptosis, similar to LY294002. On the whole, the present study demonstrates that CKI reduces cardiomyocyte apoptosis, promotes healthy cardiac function and attenuates Ang II‑mediated HF. These ameliorative effects may be associated with the inhibition of the PI3K/Akt pathway.


[Postmortem diagnosis of ventricular fibrillation in acute coronary insufficiency].
Occlusion of coronary artery in dogs has revealed differences in K and Na postmortal distributions in the heart and skeletal muscles after ventricular fibrillation and acute coronary insufficiency. A more dramatic reduction of K and Na content in the heart and skeletal muscles was noted in death caused by heart failure than death caused by ventricular fibrillation. The analysis of autopsy samples showed a more marked reduction in K content in a possible ischemic area (the middle third of anterior wall of the left ventricle) during slow death with short agonal periods as compared to sudden death and a significant reduction of K content in skeletal muscle during slow death in contrast to the absence of changes in sudden death. K and Na measurements in the myocardium and skeletal muscle can be used in addition to catamnesis data for determining the cause of sudden death.


A qualitative study of perceptions of control over potential causes of death and the sources of information that inform perceptions of risk.
Investigating perceptions of control over mortality risk may be fundamental to understanding health behaviours and tackling socioeconomic gradients in health. Few studies have explored perceptions of control over different causes of death and there is a lack of qualitative risk research. Our aim was to examine participants' perceptions of control over potential causes of death and the sources that inform perceptions of risk. We conducted semi-structured interviews with 24 participants (14 female and 10 male) and conducted a template analysis to analyse the transcripts. We identified six themes to represent participants' perceptions of control over potential mortality risks and the sources that inform these perceptions: Health-Related Mortality Risks, External Causes of Risk, Finding Balance, Family Medical History, Online Sources of Risk and Health-Related Information, and Health Misinformation. Dying from heart disease was broadly reported as being a controllable risk, whereas cancer was mostly discussed as uncontrollable. Gender-specific cancers were perceived as posing a significant risk to life, however controlling this risk was discussed in terms of screening and treatment, not prevention. Family medical history was discussed as an informative source for longevity predictions, but less so for specific causes of death. Most risk information is retrieved from 'Dr Google', though trusted sources, such as NHS websites, are used for validation. Health misinformation online was seen as a problem experienced by other people, rather than the individual. Causal pathways between behaviours and specific cancers may not be obvious to individuals. Messages emphasising the broader links between diet, alcohol and general cancer risk may highlight the controllability of cancer risk through improved health behaviours. Furthermore, given the rise in health misinformation, and the belief that it is other people not ourselves that are typically susceptible to believing misinformation online, further attempts are needed to combat this growing 'infodemic'.


Effects of feedback on legally intoxicated drivers.
College-aged patrons leaving a drinking establishment were given feedback about their blood alcohol level (BAL): 24 were administered a Breathalyzer and were then read a statement on the consequences of driving with their BAL; 21 were shown a large chart and had to determine their own BAL from their weight and number of drinks consumed; and 21 were given no feedback. The two feedback groups were later collapsed. The subjects were also followed unobtrusively to determine whether they drove away from the premises. A total of 24 of the feedback subjects (47%) were legally intoxicated, but 83% of this group nonetheless drove after learning that they were legally intoxicated. In addition, when self-reports of consumption were compared with Breathalyzer BALs, a correlation of .82 was obtained.


Serum metabolic profiling and features of papillary thyroid carcinoma and nodular goiter.
Thyroid carcinoma is a common endocrine malignancy worldwide, accounting for approximately 1% of all diagnosed cancers and about 91.5% of the malignancies of head and neck. However, differentiating malignant thyroid nodules from benign ones remains a diagnostic challenge. Thus, novel molecular markers that enable non-invasive diagnostics for malignant thyroid nodules are urgently needed. In the present study, a metabonomic investigation based on liquid chromatography-LTQ Orbitrap mass spectrometry was employed for serum metabolic profiling of 30 cases of papillary thyroid carcinomas (PTC), 80 cases of nodular goiters (benign thyroid nodules) and 30 cases of healthy controls. According to the results of multivariate statistical data analysis, the significantly changed metabolites among these three groups were defined. It was found that most of these metabolites decreased in the sera of both malignant and benign thyroid cases due to the increased metabolic rate, which is in accordance with clinical features. The major metabolic differences between benign and malignant nodules occurred in lipid metabolism. Especially, the content of 3-hydroxybutyric acid, an intermediate product of fatty acid metabolism, was much higher in the PTC group than that in the nodule goiter and control groups, indicating its potential as a diagnostic marker for PTC and nodular goiters. These results show that the serum metabolic profiling method is a powerful tool for distinguishing thyroid carcinoma from nodular goiter and healthy controls.