Spontaneous coronary artery dissection: a case series and literature review.
Spontaneous coronary artery dissection (SCAD) is a rare and often lethal cause of acute coronary syndrome, which typically affects young women and otherwise healthy individuals. SCAD can be diagnosed in patients undergoing coronary angiography and can be underestimated. Special techniques such as optical coherence tomography (OCT) and intravascular ultrasound should be used when there is suspicion of the condition. In the majority of cases, the left anterior descending (LAD) artery is involved; however, a few cases of the right coronary artery (RCA) involvement have been reported. This article describes three cases of SCAD in women of different ages, all presenting with chest pain. Coronary angiography in conjunction with OCT was used for diagnosis in two of the cases. One of the patients had involvement of the proximal RCA and underwent percutaneous coronary intervention, whereas the other two patients had mid-LAD disease and were treated conservatively with medical therapy. Presently, there are no specific guidelines for the treatment of SCAD, and therapy is individualized according to extent and severity of the condition.


[Serotonin, two faces of a unique molecule in the regulation of bone mass].
During the last 20 years, the emergence of sophisticated genetic tools has extraordinarily improved our understanding of a large number of physiological functions, among which the physiology of the skeleton. Bone, recently described as an endocrine organ, has the ability to constantly renew itself through bone remodeling, which requires a constant supply of energy. Hence, we hypothesized that there must be a coregulation of bone mass and energy metabolism, and focused on leptin, an adipocyte-derived hormone, which regulates both energy metabolism and bone remodeling through a central relay. Through a careful analysis of leptin neuronal targets, we unraveled that leptin regulation of bone mass occurs indirectly by inhibiting serotonin release and synthesis in neurons of the brainstem. Surprisingly, we observed that the other pool of serotonin, produced in enterochromaffin cells of the duodenum, negatively regulates bone mass accrual. Thus, serotonin is a molecule with two distinct functional identities depending on its site of synthesis. Finally, a recent study provides a proof of principle that inhibiting gut-derived serotonin (GDS) biosynthesis could become a new anabolic treatment for osteoporosis. double dagger.


Changing dietary electrolyte balance for dairy cows in cool and hot environments.
Two Latin square studies, each containing eight primiparous cows (four Holstein, four Jersey), were conducted to determine the effect of changing dietary electrolyte balance during cool and hot environmental conditions on performance of lactating dairy cows. Electrolyte balance, expressed as Na + K - Cl in milliequivalents per kilogram of diet, was altered by changing K and Cl content in the diet using potassium bicarbonate or calcium chloride. Maximum and minimum temperatures averaged 26.7 and 15.0 degrees C during the cool phase and 32.3 and 22.5 degrees C during the hot phase of the study. Milk yield improved linearly with increasing electrolyte balance with nonsignificant treatment by phase interaction, whereas DMI of cows improved quadratically with increasing dietary electrolyte balance. A treatment by phase interaction for DMI was detected, although intake of DM reached a plateau at a similar dietary electrolyte balance during the cool and hot phases. Body (milk) temperature of cows appeared to be related to the level of feed consumed and varied by treatment within phase. Body (milk) temperature was higher during the hot phase of the experiment. Blood bicarbonate and pH were lowest in cows offered the low electrolyte balance (high Cl) diet, and blood and urinary Na + K-Cl increased linearly with increasing dietary electrolyte balance. The response to dietary electrolyte balance appeared to be mediated through blood buffering and the impact on physiologic systems of the cow.


Microangiopathy of the inner ear, retina, and brain (Susac syndrome): report of a case.
Microangiopathy of the inner ear, retina, and brain was first described in 1979 by John O. Susac. Since then, approximately 60 cases have been reported. Otolaryngologists must be aware of this syndrome, in which cochleovestibular symptoms are an important part of the diagnosis. In this article, we report a new case of Susac syndrome and discuss the diagnosis, physiopathologic characteristics, and treatment of this disease.


C-terminal heptapeptide of gastrin inhibits astrocytomas motility by interacting with a new gastrin binding site.
It is well known that the amidated C-terminal part of gastrin is crucial for its interaction with the classical seven transmembrane domain receptors CCK-1 or CCK-2. Nevertheless, over the past 10 years, several groups have characterized new binding sites using peptides related to gastrin (particularly glycine-extended forms of gastrin) on various tumoral and nontumoral cell lines. In the present study, we focused on the human astrocytic tumoral cell line U373. Although it has been described that gastrin was able to inhibit the motility of these cells, we were unable to detect any classical CCK/gastrin receptor. On the other hand, by using the radiolabeled C-terminal heptapeptide of gastrin ((125)I-G-7), we evidenced a new binding site that possessed a pharmacological profile different from the classical CCK/gastrin receptors. This new gastrin binding site seemed to be coupled to G proteins and be implicated in c-Fos transcription gene. Moreover, we showed that G-7 was able to induce a strong inhibition of U373 cell migration, a crucial biological effect when we know that astrocytoma cells' migration in brain parenchyma constitutes a major feature of malignancy in astrocytic tumors.


Brain-reactive autoantibody levels in the sera of ageing autoimmune mice.
Brain-reactive autoantibodies are thought to play an important role in mediating central nervous system (CNS) disorders in systemic lupus erythematosus (SLE). In this paper the developmental occurrence of these antibodies in the sera of autoimmune mice, i.e. NZB, NZB/W, MRL/l and BXSB mice were examined. All murine strains tested, whether autoimmune or not, showed some degree of serum reactivity toward brain antigens. Autoimmune mice, however, displayed higher levels of serum brain-reactive antibodies, and at earlier ages, than non-autoimmune mice. Immunofluorescence assays against brain sections and adsorption assays, with both neural and non-neural tissue, indicated a heterogeneity in the specificity of the populations of brain-reactive antibodies present. These studies provide an important step in characterizing the appearance and diversity of brain-reactive autoantibodies, with the goal of better understanding their significance and potential role in mediating CNS dysfunction in SLE.


Single-walled carbon nanotubes coated with ZnO by atomic layer deposition.
The possibility of ZnO deposition on the surface of single-walled carbon nanotubes (SWCNTs) with the help of an atomic layer deposition (ALD) technique was successfully demonstrated. The utilization of pristine SWCNTs as a support resulted in a non-uniform deposition of ZnO in the form of nanoparticles. To achieve uniform ZnO coating, the SWCNTs first needed to be functionalized by treating the samples in a controlled ozone atmosphere. The uniformly ZnO coated SWCNTs were used to fabricate UV sensing devices. An UV irradiation of the ZnO coated samples turned them from hydrophobic to hydrophilic behaviour. Furthermore, thin films of the ZnO coated SWCNTs allowed us switch p-type field effect transistors made of pristine SWCNTs to have ambipolar characteristics.


An update on the efficacy of psychological therapies in the treatment of obsessive-compulsive disorder in adults.
We conducted a review to provide an update on the efficacy of psychological treatments for OCD in general and with regard to specific symptom presentations. The PubMed and PsycINFO databases were searched for randomized controlled trials (RCTs) published up to mid February 2012. Forty-five such studies were identified. Exposure and response prevention (ERP) and cognitive-behavioral therapy (CBT) were found to be efficacious and specific for OCD. More purely cognitive interventions that did not include ERP or behavioral experiments were found to be possibly efficacious, as were Acceptance and Commitment Therapy, Motivational Interviewing as an adjunct to the established treatments, Eye Movement Desensitization and Reprocessing, and Satiation Therapy. There was little support for Stress Management or Psychodynamic Therapy. Although the majority of the studies recruited mixed or unspecified samples of patients and did not test for moderation, CBT was efficacious for obsessional patients who lacked overt rituals. One more purely cognitive intervention named Danger Ideation Reduction Therapy was found to be possibly efficacious for patients with contamination obsessions and washing compulsions. Although ERP and CBT are the best established psychological treatments for OCD, further research is needed to help elucidate which treatments are most effective for different OCD presentations.


Influence of the granulation technique and starting material properties on the lubricating effect of granular magnesium stearate.
Magnesium stearate has been granulated in four ways to produce lubricant granulations with different properties. The lubricating properties, as well as the tablet properties with the granulated lubricant, were evaluated on tablets prepared from a mixture of dicalcium phosphate, corn starch and microcrystalline cellulose. The lubricating effect of the magnesium stearate granulations showed a similar pattern regardless of the granulation technique used except for a granulation with providone. Increasing the particle size of the magnesium stearate granulation increased the amount of lubricant required to obtain lubrication similar to powdered magnesium stearate. Variations in the specific surface area of the starting materials could be masked by using them in granular form.


Prognostic nomograms to predict oncological outcome of thyroid cancers.
Thyroid cancers represent a conglomerate of diverse histological types with equally variable prognosis. There is no reliable prognostic model to predict the risks of relapse and death for different types of thyroid cancers. The purpose of this study was to build prognostic nomograms to predict individualized risks of relapse and death of thyroid cancer within 10 years of diagnosis based on patients' prognostic factors. Competing risk subhazard models were used to develop prognostic nomograms based on the information on individual patients in a population-based thyroid cancer cohort followed up for a median period of 126 months. Analyses were conducted using R version 2.13.2. The R packages cmprsk10, Design, and QHScrnomo were used for modeling, developing, and validating the nomograms for prediction of patients' individualized risks of relapse and death of thyroid cancer. This study was performed at CancerCare Manitoba, the sole comprehensive cancer center for a population of 1.2 million. Participants were a population-based cohort of 2306 consecutive thyroid cancers observed in 2296 patients in the province of Manitoba, Canada, during 1970 to 2010. Outcomes were discrimination (concordance index) and calibration curves of nomograms. Our cohort of 570 men and 1726 women included 2155 (93.4%) differentiated thyroid cancers. On multivariable analysis, patient's age, sex, tumor histology, T, N, and M stages, and clinically or radiologically detectable posttreatment gross residual disease were independent determinants of risk of relapse and/or death. The individualized 10-year risks of relapse and death of thyroid cancer in the nomogram were predicted by the total of the weighted scores of these determinants. The concordance indices for prediction of thyroid cancer-related deaths and relapses were 0.92 and 0.76, respectively. The calibration curves were very close to the diagonals. We have successfully developed prognostic nomograms for thyroid cancer with excellent discrimination (concordance indices) and calibration.


Clinical benefits after the implementation of a multimodal perioperative protocol in elderly patients.
Multimodal protocol of perioperative care may enhance recovery after surgery. Based on evidence these new routines of perioperative care changed conventional prescriptions in surgery. To evaluate the results of a multimodal protocol (ACERTO protocol) in elderly patients. Non-randomized historical cohort study was performed at the surgical ward of a tertiary university hospital. One hundred seventeen patients aged 60 and older were submitted to elective abdominal operations under either conventional (n = 42; conventional group, January 2004-June 2005) or a fast-track perioperative protocol named ACERTO (n = 75; ACERTO group, July 2005-December 2007). Main endpoints were preoperative fasting time, postoperative day of re-feeding, volume of intravenous fluids, length of hospital stay and morbidity. The implantation of the ACERTO protocol was followed by a decrease in both preoperative fasting (15 [8-20] vs 4 [2-20] hours, P<0.001) and postoperative day of refeeding (1st [1st-10th] vs 0 [0-5th] PO day; P<0.01), and intravenous fluids (10.7 [2.5-57.5] vs 2.5 [0.5-82] L, P<0.001). The changing of protocols reduced the mean length of hospital stay by 4 days (6[1-43] vs 2[1-97] days; P = 0.002) and surgical site infection rate by 85.7% (19%; 8/42 vs 2.7%; 2/75, P<0.001; relative risk = 1.20; 95% confidence interval = 1.03-1.39). Per-protocol analysis showed that hospital stay in major operations diminished only in patients who completed the protocol (P<0.01). The implementation of multidisciplinary routines of the ACERTO protocol diminished both hospitalization and surgical site infection in elderly patients submitted to abdominal operations.


Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways.
Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines, yet the relative contribution of interferon (IFN)-gamma, interleukin (IL)-17 and IL-22 on disease pathogenesis is still unknown. In this study, we sought to identify the cytokines produced by skin-resident T cells in normal skin, localize the receptors for these cytokines, and examine how these cytokines alter gene expression profiles of the cells bearing cognate receptors. We used intracellular cytokine staining and flow cytometry to evaluate T cell cytokine production, and immunohistochemistry and double-label immunofluorescence to localize cytokine receptors in skin. Gene array analysis of cytokine-treated keratinocytes was performed using moderated paired t-test controlling for false discovery rate using the Benjamini-Hochberg procedure. We demonstrate that T-helper cells producing IL-17, IL-22 and/or IFN-gamma, as well as the cells bearing cognate cytokine receptors, are present in normal human skin. Keratinocytes stimulated with IL-17 expressed chemokines that were different from those induced by IFN-gamma, probably contributing to the influx of neutrophils, dendritic cells and memory T cells into the psoriatic lesion. In contrast, IL-22 downregulated genes associated with keratinocyte differentiation and caused epidermal alterations in an organotypic skin model. Our results suggest that the Th17 cytokines IL-17 and IL-22 mediate distinct downstream pathways that contribute to the psoriatic phenotype: IL-17 is more proinflammatory, while IL-22 retards keratinocyte differentiation.


Does being accompanied make a difference in communication during breast cancer consultations? Results from a multi-centered randomized controlled trial.
This study is based on a multi-centered RCT conducted on breast cancer patients during their first consultation with an oncologist. The main aim was to evaluate whether the introduction of a communication tool (i.e., the Question Prompt Sheet or Question Listing), with or without a companion, impacted the number of questions asked by patients during the consultation, and subsequent psychological and relational outcomes. The sample consisted of 324 breast cancer patients who were randomly placed into one of the two intervention groups: Question Prompt Sheet or Question Listing. Before and after the consultation, patients completed a set of standardized instruments: Satisfaction with decisions made during the consultation (SWD), Shared Decision Making Questionnaire (SDMQ-9), Patient Enablement Instrument (PEI), Patient Health Questionnaire Depression scale (PHQ-9), General Health Questionnaire (GHQ-12). The results indicate that the number of questions asked during the consultation was higher when a Question Listing was provided and when the patient was unaccompanied. Unaccompanied patients asked more questions in both groups and had significantly lower scores than accompanied on the GHQ-12 and on the PHQ-9, indicating lower clinical symptomatology. Results are in contrast with previous literature, indicating that being unaccompanied help patients to interact more with the oncologist. Further studies are needed to evaluate how the presence or not of a companion really impacts breast cancer patients during their first consultation with an oncologist. ClinicalTrials.gov NCT01510964.


Expression and role of TRPC proteins in human platelets: evidence that TRPC6 forms the store-independent calcium entry channel.
Store-operated Ca(++) entry (SOCE) is thought to comprise the major pathway for Ca(++) entry in platelets. Recently, a number of transient receptor potential (TRP) proteins, which have been divided into 3 groups (TRPC, TRPM, and TRPV), have been suggested as SOCE channels. We report the expression and function of TRPC proteins in human platelets. TRPC6 is found at high levels and TRPC1 at low levels. Using purified plasma (PM) and intracellular membranes (IM), TRPC6 is found in the PM, but TRPC1 is localized to the IM. Using Fura-2-loaded platelets, we report that, in line with TRPC6 expression, 1-oleoyl-2-acetyl-sn-glycerol (OAG) stimulated the entry of Ca(++) and Ba(2+) independently of protein kinase C. Thrombin also induced the entry of Ca(++) and Ba(2+), but thapsigargin, which depletes the stores, induced the entry of only Ca(++). Thus, thrombin activated TRPC6 via a SOCE-independent mechanism. In phosphorylation studies, we report that neither TRPC6 nor TRPC1 was a substrate for tyrosine kinases. TRPC6 was phosphorylated by cAMP-dependent protein kinase (cAMP-PK) and associated with other cAMP-PK substrates. TRPC1 was not phosphorylated by cAMP-PK but also associated with other substrates. Activation of cAMP-PK inhibited Ca(++) but not Ba(2+) entry induced by thrombin and neither Ca(++) nor Ba(2+) entry stimulated by OAG. These results suggest that TRPC6 is a SOCE-independent, nonselective cation entry channel stimulated by thrombin and OAG. TRPC6 is a substrate for cAMP-PK, although phosphorylation appears to not affect cation permeation. TRPC1 is located in IM, suggesting a role at the level of the stores.


Mycotoxigenic moulds and mycotoxins in flours consumed in Turkey.
Aflatoxins (AFs) and ochratoxin A (OTA) are metabolites produced by several fungi of the genera Aspergillus and Penicillium and have been found to contaminate human foods and animal feeds. The aim of this study was to investigate the abundance and diversity of total microfungi and mycotoxigenic fungi in 25 samples of different grain-based flours from four regions of Turkey (Thrace and Central, Northwest and West Anatolia) and to evaluate the level of AF and OTA contamination. Microscopic and polymerase chain reaction analyses were used to identify fungi, while high-performance liquid chromatography was used for the detection of AFs and OTA. A total of 551 fungal strains were obtained from the samples and identified morphologically and by multi-locus gene sequencing. All samples were contaminated with fungi ((2-4.8) × 10(4) colony-forming units g(-1) ) and three of them exceeded the European Commission (EC) limits. The data also revealed that 70.5 and 14.7% of the fungal isolates were positive for AF and OTA production respectively. In addition, 21 samples were contaminated by AFs (14.98 and 22.4 µg kg(-1) for AFB1 ) and OTA (3.02 and 4.76 µg kg(-1) ) and three of them exceeded the EC limits. This study is the first report on problems with the occurrence of microfungi, mycotoxin contamination, AFs and OTA in different grain-based flour samples from Turkey and highlights developable points of current limits for food and public health safety.


Multi-disciplinary integration of networking through the RNAS+: Research on other target diseases.
In 2005, the network decided to increase its number of target diseases to include other helminthic zoonoses such as fascioliasis, clonorchiasis, opisthorchiasis, paragonimiasis and cysticercosis and in the process expanding membership to include South Korea, Vietnam, Thailand and Japan. NTDs were eventually included as awareness is heightened on these diseases affecting poor and developing countries. Researches on clonorchiasis and opisthorchiasis unravel the mechanism by which these diseases eventually predispose to cholangiocarcinoma. The liver cancer associated with these liver fluke infections necessitate the need to clarify the global burden of disease of these infections. The magnitude of these liver fluke diseases in endemic countries like China, Vietnam, Laos, Cambodia and Thailand is described. Success in elimination of lymphatic filariasis in PR China and Cambodia is highlighted to show how intensified multisectoral collaboration and strong political become strong ingredients in elimination of parasitic diseases like LF. New advances are presented that clarify species and strain differences in Fasciola spp., Paragonimus spp., Taenia spp. and Echinococcocus spp. Conventional diagnostic techniques are compared with new serologic techniques that are being developed. New control strategies such as the Lawa model are presented.


Granulocyte-macrophage colony-stimulating factor is a major macrophage fusion factor present in conditioned medium of concanavalin A-stimulated spleen cell cultures.
In 1983, we reported that the conditioned medium (CM) of spleen cell cultures treated with Con A greatly induced fusion of mouse alveolar macrophages within 2 to 3 days at a very high rate of more than 80% (Proc. Natl. Acad. Sci. USA 80:5583, 1983). In the course of examining macrophage fusion factors (MFF) present in Con A-CM, we found that IL-4 induced fusion of alveolar macrophages with a time course similar to that induced by Con A-CM. However, the maximal fusion rate induced by IL-4 (4 ng/ml) was about 35%. Furthermore, the fusion induced by Con A-CM was blocked only partially by adding IL-4 antibody, indicating that there are unknown MFF other than in Con A-CM. Of several other cytokines produced by Con A-stimulated spleen cells, IL-6 (20 ng/ml), IFN-gamma (45 ng/ml) and granulocyte-macrophage (GM)-CSF (10 ng/ml) greatly potentiated the fusion induced by 4 ng/ml of IL-4. The assay of these cytokines in Con A-CM proved that it contained 0.44 +/- 0.04 ng/ml of IL-4, 1.0 +/- 0.24 ng/ml of IL-6, 9.1 +/- 0.07 ng/ml of IFN-gamma, and 11.6 +/- 1.66 ng/ml of GM-CSF. When the potentiating effects of IL-6, IFN-gamma and GM-CSF on macrophage fusion were examined in the presence of 0.4 ng/ml of IL-4, only GM-CSF increased the fusion rate to the maximal level induced by Con A-CM at its physiologic concentration (10 ng/ml). The macrophage fusion induced by Con A-CM was greatly suppressed by adding antibody against GM-CSF. GM-CSF had a biphasic effect on growth and fusion, depending on its dose levels used: 0.01 to 0.1 ng/ml increased proliferation without inducing fusion and 10 ng/ml preferentially induced fusion. There was a negative relationship between macrophage growth and fusion. IL-4 was a potent inhibitor of proliferation of macrophages induced by GM-CSF. These results clearly indicate that GM-CSF is a major MFF present in Con A-CM.


Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle.
Obesity develops when caloric intake exceeds metabolic needs. Promoting energy expenditure represents an attractive approach in the prevention of this fast-spreading epidemic. Here, we report a novel pharmacological strategy in which a natural compound, narciclasine (ncls), attenuates diet-induced obesity (DIO) in mice by promoting energy expenditure. Moreover, ncls promotes fat clearance from peripheral metabolic tissues, improves blood metabolic parameters in DIO mice, and protects these mice from the loss of voluntary physical activity. Further investigation suggested that ncls achieves these beneficial effects by promoting a shift from glycolytic to oxidative muscle fibers in the DIO mice thereby enhancing mitochondrial respiration and fatty acid oxidation (FAO) in the skeletal muscle. Moreover, ncls strongly activates AMPK signaling specifically in the skeletal muscle. The beneficial effects of ncls treatment in fat clearance and AMPK activation were faithfully reproduced in vitro in cultured murine and human primary myotubes. Mechanistically, ncls increases cellular cAMP concentration and ADP/ATP ratio, which further lead to the activation of AMPK signaling. Blocking AMPK signaling through a specific inhibitor significantly reduces FAO in myotubes. Finally, ncls also enhances mitochondrial membrane potential and reduces the formation of reactive oxygen species in cultured myotubes.


Inhibitory effect of HIV-1 Tat protein on the sodium-D-glucose symporter of human intestinal epithelial cells.
The pathophysiology of HIV-1-related intestinal dysfunction is largely unknown. We previously found that the transactivator factor peptide (Tat) produced by HIV-1 induces ion secretion and inhibits cell proliferation in human enterocytes. Because sugar malabsorption is a frequent feature in AIDS patients, we evaluated whether Tat inhibits intestinal glucose absorption. We measured Na-D-glucose symporter (SGLT-1) activity and determined its phenotypic expression in Caco-2 cells, in the presence and absence of Tat, in uptake experiments using a non-metabolized radiolabelled glucose analogue, and by western blot analysis, respectively. alpha-Tubulin staining was used to study the effects exerted by Tat on cell structure. Tat dose dependently inhibited glucose uptake by human enterocytes. This effect was prevented by anti-Tat polyclonal antibodies and by L-type Ca channels agonist Bay K8644. Western blot analysis of cellular lysates and brush-border membrane preparations showed that Tat induced SGLT-1 missorting. Tat also caused a dramatic decrease in alpha-tubulin staining, which indicates dysruption of the cytoskeleton organization. Tat acutely impairs intestinal glucose absorption through SGLT-1 missorting. This result indicates that Tat is directly involved in AIDS-associated intestinal dysfunction.


Cell growth on tissue-engineering scaffolds prepared by gamma irradiation grafting of N-vinyl-2-pyrrolidone onto polyvinyl alcohol.
In the field of tissue engineering, promoting cell attachment and proliferation in polymer matrices is an attractive challenge for treating patients suffering from the loss or dysfunction of tissues or organs. In this study we have investigated the effect of grafting N-vinyl-2-pyrrolidone (NVP) by gamma irradiation onto polyvinyl alcohol (PVA), a highly hydrophilic and non-toxic material. PVA scaffolds were prepared by freeze-thaw and progen (glycerol) methods. In the first method, samples were freeze-thawed for three consecutive cycles at -25 degrees C (90 min) and room temperature (60 min); in the latter, 0-40% glycerol was used as progen. Gamma irradiation of the scaffolds in the presence of NVP was performed at different concentrations (2, 3, 4 and 6%) with 5, 10 and 15 kGy 60Co. The highest percentage of grafting was obtained at 4% NVP solution and 15 kGy. Cell attachment was optimal for the scaffolds prepared using freeze-thaw and glycerol methods with 3.8% and 2.7% polyvinyl pyrrolidone (PVP), respectively.


Credit card debt, stress and key health risk behaviors among college students.
To examine cross-sectional associations between credit card debt, stress, and health risk behaviors among college students, focusing particularly on weight-related behaviors. Random-sample, mailed survey. Undergraduate and graduate students (n = 3206) attending a large public university. Self-reported health indicators (e.g., weight, height, physical activity, diet, weight control, stress, credit card debt). More than 23% of students reported credit card debt > or = $1000. Using Poisson regression to predict relative risks (RR) of health behaviors, debt of at least $1000 was associated with nearly every risk indicator tested, including overweight/obesity, insufficient physical activity, excess television viewing, infrequent breakfast consumption, fast food consumption, unhealthy weight control, body dissatisfaction, binge drinking, substance use, and violence. For example, adjusted RR [ARR] ranged from 1.09 (95% Confidence interval [CI]: 1.02-1.17) for insufficient vigorous activity to 2.17 (CI: 0.68-2.82) for using drugs other than marijuana in the past 30 days. Poor stress management was also a robust indicator of health risk. University student lifestyles may be characterized by a variety of coexisting risk factors. These findings indicate that both debt and stress were associated with wide-ranging adverse health indicators. Intervention strategies targeting at-risk student populations need to be tailored to work within the context of the many challenges of college life, which may serve as barriers to healthy lifestyles. Increased health promotion efforts targeting stress, financial management, and weight-related health behaviors may be needed to enhance wellness among young adults.


alphaB-crystallin regulation of angiogenesis by modulation of VEGF.
alphaB-crystallin is a chaperone belonging to the small heat shock protein family. Herein we show attenuation of intraocular angiogenesis in alphaB-crystallin knockout (alphaB-crystallin(-/-)) mice in 2 models of intraocular disease: oxygen-induced retinopathy and laser-induced choroidal neovascularization. Vascular endothelial growth factor A (VEGF-A) mRNA and hypoxia inducible factor-1alpha protein expression were induced during retinal angiogenesis, but VEGF-A protein expression remained low in alphaB-crystallin(-/-) retina versus wild-type mice, whereas VEGF-R2 expression was not affected. Both alphaB-crystallin and its phosphorylated serine59 formwere expressed, and immunoprecipitation revealed alphaB-crystallin binding to VEGF-A but not transforming growth factor-beta in cultured retinal pigment epithelial (RPE) cells. alphaB-crystallin and VEGF-A are colocalized in the endoplasmic reticulum in RPE cells under chemical hypoxia. alphaB-crystallin(-/-) RPE showed low VEGF-A secretion under serum-starved conditions compared with wild-type cells. VEGF-A is polyubiquitinated in control and alphaB-crystallin siRNA treated RPE; however, mono-tetra ubiquitinated VEGF-A increases with alphaB-crystallin knockdown. Endothelial cell apoptosis in newly formed vessels was greater in alphaB-crystallin(-/-) than wild-type mice. Proteasomal inhibition in alphaB-crystallin(-/-) mice partially restores VEGF-A secretion and angiogenic phenotype in choroidal neovascularization. Our studies indicate an important role for alphaB-crystallin as a chaperone for VEGF-A in angiogenesis and its potential as a therapeutic target.


High- and low-threshold models of the relationship between response time and confidence.
The author compared high- and low-threshold discrete-state models of recognition memory in terms of their ability to account for confidence and response time (RT) data. The 2-high threshold (2HT), 1-low threshold (1LT), and 2-low threshold (2LT) models were clearly distinguished by the commonly observed inverted-U pattern whereby RTs are longer for low-confidence than high-confidence responses on both sides of the confidence scale (correct responses and errors). The 2HT model was able to match the RT-confidence relationship for correct responses, but it was unable to match the same relationship for errors. The 1LT model could not match the RT-confidence relationship for either correct responses or errors. Only the 2LT model was able to match the full pattern. The differences between models were driven by their fundamental assumptions about memory retrieval: only the 2-threshold models could produce an RT-confidence relationship by mixing relatively fast responses from a detection state with relatively slow responses from an uncertain ("guess") state, and only the 2LT model could do so for both correct and error responses because it allows misleading detection. Quantitative fits also showed that the 1LT model could not account for changes in confidence-rating distributions across memory-strength conditions, and thus this model performed substantially worse than the other two models even when RT data were not considered. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


The effects of nimodipine on the EEG of substance abusers.
Cocaine abusers have increased EEG beta and areas of reduced cortical blood flow. Since, nimodipine has neuroprotective effects and increases blood flow, we investigated the efficacy of single and multiple doses of the nimodipine in normalizing the EEG of substance abusers. Fourteen subjects received single (0, 30, 60 mg) and eleven received multiple daily (up to 150 mg in 12 hours) doses of nimodipine to determine whether this drug would increase EEG alpha and decrease beta in substance abusers. The EEG was recorded from eight scalp locations (F3, C3, P3, O1, F4, C4, P4 and O2) for three minutes during eyes closed, and eyes open conditions. Single and multiple doses of nimodipine produced significant increases in EEG alpha and decreases in EEG beta in the eyes open condition. Thus, nimodipine may have potential therapeutic implications in the treatment of cocaine dependence. Chronic nimodipine dosing in cocaine-dependent individuals is now needed to confirm its efficacy in the treatment of cocaine dependence.


[Minimally invasive percutaneous plate osteosynthesis technique for treatment of Neer II, III parts fracture of proximal humerus].
To evaluate the clinical significance of minimally invasive percutaneous plate osteosynthesis (MIPPO) applied in Neer II, III parts fractures of proximal humerus. The clinical data were retrospectively analyzed, from 30 patients with Neer II, III parts fractures of proximal humerus in accordance with selection criteria, who were treated with manual reduction and plaster external fixation (11 cases, non-operative group) or with MIPPO (19 cases, operative group) between January 2008 and May 2010. In non-operative group, there were 6 males and 5 females with an average age of 60 years (range, 56-80 years) and with an average time of 10 hours (range, 3-24 hours) between injury and reduction, including 8 cases of Neer II and 3 cases of Neer III. In operative group, there were 13 males and 6 females with an average age of 65 years (range, 45-78 years) and with an average time of 3 days (range, 1-5 days) between injury and operation, including 9 cases of Neer II and 10 cases of Neer III. There was no significant difference in gender, age, fracture type, and time from injury to operation (P > 0.05). The shoulder joint function before and after treatments was evaluated according to Constant-Murley Score (CMS) and American Shoulder and Elbow Surgeons' Form (ASES) scoring systems. Thirty patients were followed up. In operative group, the follow-up time ranged from 11 to 18 months (mean, 12 months); all incisions healed by first intention with no complication of internal fixation failure, infection, or nerve injury. In non-operative group, the follow-up time ranged from 9 to 15 months (mean, 11 months). The X-ray films showed that fractures healed without humeral head necrosis in 2 groups. The bone healing time in operative group and non-operative group was (11.47 +/- 2.48) weeks and (11.82 +/- 2.44) weeks, respectively, showing no significant difference (t = 0.369, P = 0.889). The CMS score and ASES score at each time point after treatment were significantly better than those before treatment (P < 0.05); the CMS scores in operative group were better than those in non-operative group at 3 weeks, 3 months, and 1 year after treatment (P < 0.05); and the ASES score in operative group was better than that in non-operative group at 3 weeks and 3 months after treatment (P < 0.05), but no significant difference was found at 1 year after treatment (P > 0.05). MIPPO fixation using the locking compression plate is an effective option for Neer II, III parts fractures of proximal humerus. It can provide good functional recovery of the shoulder joint so that patients can get back to their normal life as soon as possible.


Metastasis to the midbrain. Report of two cases.
Two patients with metastasis from lung carcinoma of the midbrain are presented. The computerized tomographic (CT) findings mimicked a primary pineal tumor, but autopsy confirmed a metastatic nodule in the midbrain in both cases. The rational approach to posterior third ventricular tumors seen on CT in adulthood is discussed.


A review of the prognostic value of irrigation on root canal treatment success.
The aim of this review is to discuss the requirements for effective irrigation of the root canal system and its role in treatment outcome. A review of the literature regarding irrigants, methods of irrigation and regimens was undertaken. It indicates that irrigation is comprised of a multitude of factors, and that effective irrigant delivery and agitation achieves mechanical, chemical and microbiological functions, which are prerequisites for obtaining a clean canal system. However, most studies are ex vivo and assess intermediate outcome values rather than treatment success. Additionally, there is an absence of high-level evidence evaluating the effect of irrigation on the outcome of root canal treatment. Therefore, citing irrigation as a significant factor that affects root canal treatment success cannot be done. This highlights the need to further investigate the prognostic value of irrigation on root canal treatment success.


Hormonal interventions with psychopharmacological potential: an overview.
The better understanding of how hormones modulate cognition and behavior is associated with the application of hormones as psychotropic medications. Several natural and synthetic hormones are used as adjuncts to antidepressant medications or as treatments in their own right. We discuss pharmacotherapeutical aspects of estrogen, thyroid hormones, cortisol suppressors, and melatonin as examples of current trends in the field. In addition to the putative roles of these hormones in the treatment of affective disorders, estrogen might also be used as a cognition-enhancer, and both estrogen and thyroid hormones might have roles as mood stabilizers. The psychotropic effects of melatonin have recently received significant attention, but the exact role of that hormone still needs to be clarified.


Aseptic meningitis following cardiac transplantation: clinical characteristics and relationship to immunosuppressive regimen.
Neurologic disorders are uncommon but alarming complications of cardiac transplantation. Of 29 patients from the Utah Cardiac Transplant Program (UCTP) who had lumbar puncture because of change in neurologic function, or to assess fever of uncertain etiology, CSF pleocytosis was present in 14 patients, 4 of whom had an active infectious process involving the nervous system. In 10 other patients, CSF pleocytosis with negative cultures appeared following treatment with OKT3 monoclonal antibody. The most prominent clinical signs of this aseptic meningitis syndrome are fever and transient cognitive dysfunction.


Endogenous expression and in vitro study of CRF-related peptides and CRF receptors in the rat gastric antrum.
In vivo studies suggest that corticotrophin-releasing factor (CRF) and CRF-like peptides, urocortin 1 (UCN 1) and UCN 2, inhibit gastric emptying and stimulate colonic motility through CRF2 and CRF1 receptors, respectively. We evaluated expression and functions of CRF, UCN 1, UCN 2 and CRF1 and CRF2 receptors in the rat gastric antrum. Tissues were processed for immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). In vitro studies were performed to test the functional significance of CRF, UCN 1 and UCN 2. Some experiments were realized in the presence of specific CRF1 or CRF2 receptors antagonists. CRF1 and CRF2 receptors-like immunoreactivity (CRF1 and CRF2 receptors-LI) was localized in fibers and neurons of the myenteric ganglia. CRF1 and CRF2 receptors-LI was also found in nerve fibers distributed in the muscle layers. CRF- and UCN 1-LI was observed in neuronal cell bodies of the myenteric ganglia and in numerous nerve fibers running parallel to smooth muscle cells. Quantitative RT-PCR demonstrated UCN 2, CRF1 and CRF2 receptors expressions in both muscle layers and mucosa of the gastric antrum. Functional studies showed that CRF, UCN 1 and UCN 2 decreased antral phasic contractions. CRF(1) receptor antagonist (CP-154,526) did not block CRF-like peptides-induced inhibition of antral motility. In contrast, a CRF2 receptor antagonist (Astressin2-B) blocked the effects of CRF-like peptides on the antral muscle contractions. These results demonstrate (1) the presence of CRF, UCN and CRF1 and CRF2 receptors in the rat gastric antrum; (2) that, in vitro, CRF-like peptides inhibit phasic contractions of the antrum through CRF2 receptor. These results strongly suggest that CRF-like peptides play a major role in the regulatory mechanisms that underlie the neural control of gastric motility through CRF2 receptor.


Tolbutamide blocks Ca(2+)- and voltage-dependent K+ currents of hippocampal Ca1 neurons.
In current-clamp recordings with KMeSO4 electrodes (either whole-cell or intracellular), though tolbutamide (0.5-1 mM) did not change the resting potential, it increased both input resistance (by 12 +/- 3.8%) and spontaneous firing, and spikes were evoked by smaller depolarizing pulses. Tolbutamide reduced in a dose-dependent manner both components of post-burst afterhyperpolarizations: IC50 was 0.15 mM for medium afterhyperpolarizations and 0.33 mM for slow afterhyperpolarizations. In whole-cell recordings under voltage-clamp, 0.5-1 mM tolbutamide depressed slow outward currents by 65 +/- 5.3%. The tolbutamide-sensitive current was Ca(2+)-dependent-tolbutamide being ineffective in Mn2+, low Ca(2+)-containing medium-though tolbutamide did not significantly depress high voltage-activated Ca2+ currents. Tolbutamide reduced C-type outward currents by 45 +/- 5.9% and M-type current inward relaxations by 41 +/- 12.9%, as well as Q-type current inward relaxations by 22 +/- 5.7%. Glyburide (10 microM) did not depress afterhyperpolarizations or outward currents, even in recordings with electrodes containing 1 mM guanosine diphosphate. We conclude that the most prominent effects of 0.5-1 mM tolbutamide on CA1 neurons are caused by suppression of Ca(2+)-and voltage-dependent outward currents, including IAHP, IC and IM.


Donor kidney glomerular filtration rate and post-transplant graft function.
This study aimed to estimate the relationship between the single kidney glomerular filtration rate (SKGFR) of a planned kidney transplant and the subsequent graft function and survival of living related kidney recipients (LKRs). Of 180 LKRs with the graft functioning for more than a year, 70 patients without delayed graft function (DGF) or acute rejection (AR) were selected for the study. According to SKGFR, assessed by 99mTcDTPA, the patients were allocated into Group 1, receiving kidney with SKGFR < 50 mL/min (32 patients), and Group 2, with SKGFR > 50 mL/min (38 patients). The database included donor, recipient and transplant variables. No significant difference was found between the patient and graft survival rate, creatinine clearance (CCr) and the rate of CCr change between the groups. Additional evaluation revealed no significant influence of the ratio of SKGFR and the recipient's body weight/size on patient and graft outcome. The analysis of factors of influence on patient and graft survival and function revealed the major influence of nonimmunological factors but not of SKGFR of the transplanted kidney. Our study did not confirm the influence of SKGFR on graft function and survival in the LKRs without DGF and AR but the limited number of patients must not be disregarded.


[Investigation in field pharmacoepidemiology: a proposal for the actions of pharmacovigilance in Brazil].
The present article aims to propose and to describe the investigation in field pharmacoepidemiology as having a major role in pharmacovigilance by municipal, state and federal governments to manage drug-related reports, communication and information in the media. First, pharmacovigilance is put into context, by including its concepts, events of interest and main functions. Subsequently, field pharmacoepidemiology investigation oriented to the twelve steps is described. Then, we present a general picture of the investigation in field pharmacoepidemiology conducted in Brazil. Finally, we argue that investigation in field pharmacoepidemiology is an important tool to improve measures in pharmacovigilance and to improve patient safety in the country.


[Development of Pseudomonas aeruginosa infection in mice with trichinellosis].
The aim of this study was to estimate the development of P. aeruginosa infection in mice infected with T. spiralis or T. pseudospiralis. The investigations were carried out on the following strains of mice: C57Bl, C3H and B6C3F1. 20 days post parasitic infection P.aeruginosa were administrated by inhalation or by intraperitoneal injection. After 4 hrs development of infection in mice was evaluated (the number of bacteria in lung or in the liver tissue were counted by plating). It was found that the bacterial infection developed with the highest rate in C3H mice followed by C57B1/6, in comparison with control mice. In C3H mice infected with T. pseudospiralis, the number of bacteria was higher in lung and liver tissue, in comparison with those infected with T. spiralis. In B6C3F1 hybrid the infection rate was significantly lower after intraperitoneal administration in T. spiralis infected mice. In our experiments, the development of P. aeruginosa infection in mice with trichinellosis was dependent on the strain of mice and the routes of bacteria administration.


Stress fractures: diagnosis, treatment, and prevention.
Stress fractures are common injuries in athletes and military recruits. These injuries occur more commonly in lower extremities than in upper extremities. Stress fractures should be considered in patients who present with tenderness or edema after a recent increase in activity or repeated activity with limited rest. The differential diagnosis varies based on location, but commonly includes tendinopathy, compartment syndrome, and nerve or artery entrapment syndrome. Medial tibial stress syndrome (shin splints) can be distinguished from tibial stress fractures by diffuse tenderness along the length of the posteromedial tibial shaft and a lack of edema. When stress fracture is suspected, plain radiography should be obtained initially and, if negative, may be repeated after two to three weeks for greater accuracy. If an urgent diagnosis is needed, triple-phase bone scintigraphy or magnetic resonance imaging should be considered. Both modalities have a similar sensitivity, but magnetic resonance imaging has greater specificity. Treatment of stress fractures consists of activity modification, including the use of nonweight-bearing crutches if needed for pain relief. Analgesics are appropriate to relieve pain, and pneumatic bracing can be used to facilitate healing. After the pain is resolved and the examination shows improvement, patients may gradually increase their level of activity. Surgical consultation may be appropriate for patients with stress fractures in high-risk locations, nonunion, or recurrent stress fractures. Prevention of stress fractures has been studied in military personnel, but more research is needed in other populations.


A functional dlt operon, encoding proteins required for incorporation of d-alanine in teichoic acids in gram-positive bacteria, confers resistance to cationic antimicrobial peptides in Streptococcus pneumoniae.
Streptococcus pneumoniae is one of the few species within the group of low-G +C gram-positive bacteria reported to contain no d-alanine in teichoic acids, although the dltABCD operon encoding proteins responsible for d-alanylation is present in the genomes of two S. pneumoniae strains, the laboratory strain R6 and the clinical isolate TIGR4. The annotation of dltA in R6 predicts a protein, d-alanine-d-alanyl carrier protein ligase (Dcl), that is shorter at the amino terminus than all other Dcl proteins. Translation of dltA could also start upstream of the annotated TTG start codon at a GTG, resulting in the premature termination of dltA translation at a stop codon. Applying a novel integrative translation probe plasmid with Escherichia coli 'lacZ as a reporter, we could demonstrate that dltA translation starts at the upstream GTG. Consequently, S. pneumoniae R6 is a dltA mutant, whereas S. pneumoniae D39, the parental strain of R6, and Rx, another derivative of D39, contained intact dltA genes. Repair of the stop codon in dltA of R6 and insertional inactivation of dltA in D39 and Rx yielded pairs of dltA-deficient and dltA-proficient strains. Subsequent phenotypic analysis showed that dltA inactivation resulted in enhanced sensitivity to the cationic antimicrobial peptides nisin and gallidermin, a phenotype fully consistent with those of dltA mutants of other gram-positive bacteria. In addition, mild alkaline hydrolysis of heat-inactivated whole cells released d-alanine from dltA-proficient strains, but not from dltA mutants. The results of our study suggest that, as in many other low-G+C gram-positive bacteria, teichoic acids of S. pneumoniae contain d-alanine residues in order to protect this human pathogen against the actions of cationic antimicrobial peptides.


Ethics and the marketing authorization of pharmaceuticals: what happens to ethical issues discovered post-trial and pre-marketing authorization?
In the EU, clinical assessors, rapporteurs and the Committee for Medicinal Products for Human Use are obliged to assess the ethical aspects of a clinical development program and include major ethical flaws in the marketing authorization deliberation processes. To this date, we know very little about the manner that these regulators put this obligation into action. In this paper, we intend to look into the manner and the extent that ethical issues discovered during inspection have reached the deliberation processes. To gather data, we used the Dutch Medicines Evaluation Board database and first searched for the inspections, and their accompanying site inspection reports and integrated inspection reports, related to central marketing authorization applications (henceforth, application/s) of drugs submitted to the European Medicines Agency (EMA) from 2011 to 2015. We then extracted inspection findings that were purely of ethical nature, i.e., those that did not affect the benefit/risk balance of the study (issues related to informed consent, research ethics committees, and respect for persons). Only findings graded at least major by the inspectorate were included. Lastly, to identify how many of the ethically relevant findings (ERFs) reach the application deliberation processes, we extracted the relevant joint response assessment reports and reviewed the sections that discussed inspection findings. From 2011 to 2015, there were 390 processed applications, of which 65 had inspection reports and integrated inspection reports accessible via the database of the Dutch Medicines Evaluation Board. Of the 65, we found ERFs in 37 (56.9%). The majority of the ERFs were graded as major and half of the time it was informed-consent related. A third of these findings were related to research ethics committee processes and requirements. Of the 37 inspections with ERFs, 30 were endorsed in the integrated inspection reports as generally GCP compliant. Day 150 joint response assessment reports and Day 180 list of outstanding issues were reviewed for all 37 inspections, and none of the ERFs were carried over in any of the assessment reports or list of outstanding issues. None of the ethically relevant findings, all of which were graded as major or critical in integrated inspection reports, were explicitly carried over to the joint assessment reports. This calls for more transparency in EMA application deliberations on how ERFs are considered, if at all, in the decision-making processes.


Predictive coding of phonological rules in auditory cortex: A mismatch negativity study.
The brain is constantly generating predictions of future sensory input to enable efficient adaptation. In the auditory domain, this applies also to the processing of speech. Here we aimed to determine whether the brain predicts the following segments of speech input on the basis of language-specific phonological rules that concern non-adjacent phonemes. Auditory event-related potentials (ERP) were recorded in a mismatch negativity (MMN) paradigm, where the Finnish vowel harmony, determined by the first syllables of pseudowords, either constrained or did not constrain the phonological composition of pseudoword endings. The phonological rule of vowel harmony was expected to create predictions about phonologically legal pseudoword endings. Results showed that MMN responses were larger for phonologically illegal than legal pseudowords, and P3a was elicited only for illegal pseudowords. This supports the hypothesis that speech input is evaluated against context-dependent phonological predictions that facilitate speech processing.


An unusual case of an obtuse marginal branch supplying the left ventricular apex.
In most patients, the left anterior descending coronary artery (LAD) feeds the anterior aspect of the interventricular septum and a large segment of the anterior wall of the left ventricle. It then passes around the left ventricular apex to supply that area as well. However, in some cases, the LAD is shorter and terminates either at or before the left ventricular apex. The latter in these cases is instead supplied by a long posterior descending coronary artery (PDA), originating from the right coronary artery (RCA) at the crux, then passing along the entire length of the posterior interventricular groove, and either terminating at the apex or extending beyond it to pass upward in the anterior interventricular groove. In this case report, we describe a 50-year-old man with an apical perfusion defect on stress myocardial perfusion imaging in whom diagnostic coronary angiography revealed that the left ventricular apex was supplied by a large, obtuse marginal branch of the left circumflex coronary artery (LCX) instead of the LAD.


Emerging Status of Multidrug-Resistant Bacteria and Fungi in the Arabian Peninsula.
We aimed to identify the prevalence and emerging status of multidrug-resistant bacteria and fungi and their associated mortality in nine countries in the Arabian Peninsula. Original research articles and case studies regarding multidrug-resistant bacteria and fungi in the Arabian Peninsula, published during the last 10 years, were retrieved from PubMed and Scopus. A total of 382 studies were included as per the inclusion and exclusion criteria, as well as the PRISMA guidelines, from a thorough screening of 1705 articles, in order to analyse the emerging status and mortality. The emerging nature of >120 multidrug-resistant (MDR) bacteria and fungi in the Arabian Peninsula is a serious concern that requires continuous monitoring and immediate preventive measures. More than 50% (n = 453) of multidrug-resistant, microbe-associated mortality (n = 871) in the Arabian Peninsula was due to MDR Acinetobacter baumannii, Mycobacterium tuberculosis and Staphylococcus aureus infection. Overall, a 16.51% mortality was reported among MDR-infected patients in the Arabian Peninsula from the 382 articles of this registered systematic review. MDR A. baumannii (5600 isolates) prevailed in all the nine countries of the Arabian Peninsula and was one of the fastest emerging MDR bacteria with the highest mortality (n = 210). A total of 13,087 Mycobacterium tuberculosis isolates were reported in the region. Candida auris (580 strains) is the most prevalent among the MDR fungal pathogen in the Arabian Peninsula, having caused 54 mortalities. Active surveillance, constant monitoring, the development of a candidate vaccine, an early diagnosis of MDR infection, the elimination of multidrug resistance modulators and uninterrupted preventive measures with enhanced data sharing are mandatory to control MDR infection and associated diseases of the Arabian Peninsula. Accurate and rapid detection methods are needed to differentiate MDR strain from other strains of the species. This review summarises the logical relation, prevalence, emerging status and associated mortality of MDR microbes in the Arabian Peninsula.


Substrate recognition determinants of human eIF2α phosphatases.
Phosphorylation of the translation initiation factor eIF2α is a rapid and vital cellular defence against many forms of stress. In mammals, the levels of eIF2α phosphorylation are set through the antagonistic action of four protein kinases and two heterodimeric protein phosphatases. The phosphatases are composed of the catalytic subunit PP1 and one of two related non-catalytic subunits, PPP1R15A or PPP1R15B (R15A or R15B). Here, we generated a series of R15 truncation mutants and tested their properties in mammalian cells. We show that substrate recruitment is encoded by an evolutionary conserved region in R15s, R15A325-554 and R15B340-639. G-actin, which has been proposed to confer selectivity to R15 phosphatases, does not bind these regions, indicating that it is not required for substrate binding. Fragments containing the substrate-binding regions but lacking the PP1-binding motif trapped the phospho-substrate and caused accumulation of phosphorylated eIF2α in unstressed cells. Activity assays in cells showed that R15A325-674 and R15B340-713, encompassing the substrate-binding region and the PP1-binding region, exhibit wild-type activity. This work identifies the substrate-binding region in R15s, that functions as a phospho-substrate trapping mutant, thereby defining a key region of R15s for follow up studies.


Programming membrane fusion and subsequent apoptosis into mammalian cells.
By the delivery of specific natural or engineered proteins, mammalian cells can be programmed to perform increasingly sophisticated and useful functions. Here, we introduce a set of proteins that has potential value in cell-based therapies by programming a cell to target tumor cells. First, the delivery of VSV-G (vesicular stomatitis virus glycoprotein) allowed the cell to undergo membrane fusion with adjacent cells to form syncytia (i.e., a multinucleated cell) in conditions of low pH typically occurring at a tumor site. The formation of syncytia caused the clustering of nuclei along with an integration of the microtubule network and ER. Interestingly, the formation of syncytia between cells that are dynamically blebbing, a mode of migration preferred during tumor metastasis, resulted in the loss of these morphology changes. Lastly, the codelivery of VSV-G with L57R (an engineered photoactivated caspase-7) allowed cells to undergo low pH-dependent membrane fusion followed by blue light-dependent apoptosis. In cell-based therapies, the clearance of syncytia between tumor cells might further trigger an immune response against the tumor.


[A case of corticobasal degeneration--the usefulness of surface anatomy scatomy scanning image by MRI].
We experienced usefulness of surface anatomy scanning (SAS) image by weight-summation technique using MRI in corticobasal degeneration. The patient was a 73-year-old right-handed woman who had progressive dysarthria and clumsiness of the right hand. Neurological examination revealed mild dementia, dysarthria, buccofacial apraxia, rigidity and dystonic movement of the right upper limb. Dysarthria was guessed to be caused by buccofacial apraxia. Brain CT and MRI demonstrated atrophy of the left frontoparietal lobes, and hypoperfusion was shown in their areas by 123I-IMP SPECT. Clearly, SAS image disclosed the atrophy of the left pre- and post-central gyri that were surrounded by enlarged sulci. SAS was recently designed in Japan as a technique for visualization of brain surface structures. It is difficult to observe surface structures of cerebral gyri and sulci by conventional neuroradiological slice image, so SAS is useful for analysis of disorders affecting cerebral cortex as corticobasal degeneration.


Examining the link between posttraumatic stress disorder symptoms and dating aggression perpetration.
This study examined the role of posttraumatic stress disorder (PTSD) symptoms with respect to dating aggression perpetration among a sample of 199 undergraduates. Almost one-third of the overall sample reported physical dating aggression perpetration in the past year, and approximately 80% reported engaging in psychological dating aggression. Structural equation modeling (SEM) analyses indicated that the effects of trauma exposure on dating aggression were fully indirect via PTSD symptoms. PTSD symptoms were associated with psychological dating aggression in part through its association with anger, and alcohol problems were also directly related to this outcome. Results generalize findings from other populations suggesting the salience of trauma and PTSD symptoms in intimate relationship aggression and point to possible etiological pathways for these associations.


[Research progress of structured repair of tendon-bone interface].
In sports system, the tendon-bone interface has the effect of tensile and bearing load, so the effect of healing plays a crucial role in restoring joint function. The process of repair is the formation of scar tissue, so it is difficult to achieve the ideal effect for morphology and biomechanical strength. The tissue engineering method can promote the tendon-bone interface healing from the seed cells, growth factors, and scaffolds, and is a new direction in the field of development of the tendon-bone interface healing.


Three-dimensional acetabular orientation measurement in a reliable coordinate system among one hundred Chinese.
Determining three-dimensional (3D) acetabular orientation is important for several orthopaedic scenarios, but the complex geometries of both pelvis and acetabulum make measurements of orientation unreliable. Acetabular orientation may also differ between the sexes or racial groups. We aimed to (1) establish and evaluate a novel method for measuring 3D acetabular orientation, (2) apply this new method to a large population of Chinese subjects, and (3) report relevant characteristics of native acetabular orientation in this population. We obtained computed tomography scans taken for non-orthopaedic indications in 100 Chinese subjects (50 male, 50 female). A novel algorithm tailored to segmentation of the hip joint was used to construct 3D pelvic models from these scans. We developed a surface-based method to establish a reliable 3D pelvic coordinate system and software to semi-automatically measure 3D acetabular orientation. Differences in various acetabular orientations were compared within and between subjects, between male and female subjects, and between our subjects and subjects previously reported by another group. The reported method was reliable (intraclass correlation coefficient >0.999). Acetabular orientations were symmetrical within subjects, but ranged widely between subjects. The sexes differed significantly in acetabular anteversion (average difference, 3.0°; p < 0.001) and inclination (1.5°; p < 0.03). Acetabular anteversion and inclination were substantially smaller among our Chinese subjects than previously reported for American subjects. Thus, our method was reliable and sensitive, and we detected sex differences in 3D acetabular orientation. Awareness of differences between the sexes and races is the first step towards better reconstruction of the hip joint for all individuals and could also be applied to other orthopaedic scenarios.


Simultaneous Measurement of NH(4) Absorption and N(2) Fixation by Glycine max L. : RESPONSE TO TEMPERATURE, pH, AND EXTERNAL NITROGEN CONCENTRATION.
Ammonium absorption rates by intact nodulated and unnodulated soybean plants (Glycine max [L.] Merr., Amsoy 71) were determined from the liquid phase of a mist assay chamber. From the gas phase, simultaneous measurements of acetylene reduction rates were made from nodulated plants. Ammonium absorption capacity was consistently greater in unnodulated plants.At the beginning of flowering, plant roots were sprayed with an uptake solution ranging from 0.05 to 1.0 millimolar NH(4)Cl, and root nodules concurrently were exposed to 0.12 atmosphere acetylene. The NH(4) (+) absorption system of both nodulated and unnodulated plants were nearly saturated at 0.3 to 0.5 millimolar NH(4) (+).Increasing the pH from 4.0 to 6.8 stimulated NH(4) (+) absorption rate in both flowering and preflowering nodulated and unnodulated plants. Acetylene reduction rate was not altered by short-term exposure to increased acidity. Short-term exposure to lower absorption solution temperatures from 32 degrees C to 18 degrees C did not significantly affect NH(4) (+) absorption rate in flowering nodulated or unnodulated plants. However, acetylene reduction rate increased as the absorption solution temperature increased. The Q(10) value was 1.5 for the reaction rate. Increasing external NO(3) (-) concentration from 0.1 to 5.0 millimolar NO(3) (-) did not significantly influence the kinetics of NH(4) (+) absorption or acetylene reduction rate.


Direct catalytic enantio- and diastereoselective aldol reaction using a Zn-Zn-linked-BINOL complex: a practical synthesis of syn-1,2-diols.
[reaction: see text] The direct catalytic enantio- and diastereoselective aldol reaction with 2-hydroxy-2'-methoxyacetophenone proceeded smoothly using as little as 1 mol % of a dinuclear zinc catalyst, Zn-Zn-linked-BINOL complex 2, to afford alpha,beta-dihydroxy ketones in a highly syn-selective manner (up to syn/anti 97/3) and in excellent yields (up to 95%) and ees (up to 99%). Efficient transformations of the alpha,beta-dihydroxy ketone into an alpha,beta-dihydroxy ester and an alpha,beta-dihydroxy amide via regioselective rearrangements are also described.


Hormonal and metabolic responses of older adults to resistance training in normobaric hypoxia.
In young adults, the hormonal responses to resistance exercise are amplified by normobaric hypoxia. Hormone concentrations and metabolism are typically dysregulated with age, yet the impact of hypoxia on these responses to resistance exercise are uncharacterised. Therefore, this study aimed to characterise the acute and chronic hormonal and metabolic responses of older adults to resistance training in normobaric hypoxia. Adults aged 60-75 years completed 8 weeks of resistance training in either normoxia (20.9% O2; n = 10) or normobaric hypoxia (14.4% O2, n = 10) twice weekly at 70% of their predicted 1-repetition maximum. Growth hormone, glucose, lactate, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), cortisol, total testosterone, adrenaline, noradrenaline and dopamine were quantified at pre- and post-training, and in the 60 min following the first training session (untrained state) and the last training session (trained state). Eight weeks of training in hypoxia did not affect the resting levels of the hormones or physiological factors measured. However, hypoxia significantly blunted the acute growth hormone response in the 15 min following the last training session at week eight (43.87% lower in the hypoxic group; p = 0.017). This novel and unexpected finding requires further investigation. All other hormones were unaffected acutely by hypoxia in the 60 min following the first and the last training session. Chronic resistance training in normobaric hypoxia supresses the growth hormone response to exercise in older adults. All other hormones and metabolic markers were unaffected both acutely and chronically by hypoxia.


Influence of the sodium transport inhibition by amiloride on the transmesothelial resistance of isolated visceral sheep peritoneum.
The peritoneal mesothelium is a barrier to ion transport in peritoneal dialysis. In the present study, we used Ussing chamber experiments to investigate the effect of amiloride on the transmesothelial electrical resistance (R(TM)) of isolated visceral sheep peritoneum. Peritoneal samples from the omentum of adult sheep were isolated directly after the death of the animals and were transferred to the laboratory within 30 minutes in a cooled Krebs-Ringer bicarbonate solution (4 degrees C, pH 7.5) bubbled with 95% O2/5% CO2. A visceral peritoneal planar sheet was mounted in an Ussing-type chamber and amiloride (10(-3) mol/L) was added apically and basolaterally. The R(TM) was measured before and serially for 30 minutes after the addition of amiloride. Because active ion transport is temperature dependent, the Ussing chambers were held at 37 degrees C. The results presented are the means + standard error of 12 experiments. The control R(TM) (before the addition of amiloride) was 21.86 +/- 0.46 omega x cm2. Basolateral addition of amiloride induced, within 1 minute, an increase in R(TM) to 27.26 +/- 0.39 omega x cm2, a level that persisted throughout the experiment. When amiloride was added apically, the results were similar with a rapid rise of R(TM) to 24.18 +/- 0.9 omega x cm2 and subsequent value persistence (p < 0.05). A clear association between R(TM) and active ion transport was shown in previous studies. The results of the present study indicate rapid action of amiloride on the permeability of the visceral peritoneum. The observed increase in the R(TM) indicates the existence of amiloride-sensitive sodium channels in the visceral peritoneal membrane. The clinical implications of these results should be further investigated.


Treatment of mixed features in bipolar disorder.
Mood episodes with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)-defined mixed features are highly prevalent in bipolar disorder (BD), affecting ~40% of patients during the course of illness. Mixed states are associated with poorer clinical outcomes, greater treatment resistance, higher rates of comorbidity, more frequent mood episodes, and increased rates of suicide. The objectives of the current review are to identify, summarize, and synthesize studies assessing the efficacy of treatments specifically for BD I and II mood episodes (ie, including manic, hypomanic, and major depressive episodes) with DSM-5-defined mixed features. Two randomized controlled trials (RCTs) and 6 post-hoc analyses were identified, all of which assessed the efficacy of second-generation antipsychotics (SGAs) for the acute treatment of BD mood episodes with mixed features. Results from these studies provide preliminary support for SGAs as efficacious treatments for both mania with mixed features and bipolar depression with mixed features. However, there are inadequate data to definitively support or refute the clinical use of specific agents. Conventional mood stabilizing agents (eg, lithium and divalproex) have yet to have been adequately studied in DSM-5-defined mixed features. Further study is required to assess the efficacy, safety, and tolerability of treatments specifically for BD mood episodes with mixed features.


Phenotypic and genotypic analysis of Helicoverpa armigera nucleopolyhedrovirus serially passaged in cell culture.
Rapid accumulation of few polyhedra (FP) mutants was detected during serial passaging of Helicoverpa armigera nucleopolyhedrovirus (HaSNPV) in cell culture. 100% FP infected cells were observed by passage 6. The specific yield decreased from 178 polyhedra per cell at passage 2 to two polyhedra per cell at passage 6. The polyhedra at passage 6 were not biologically active, with a 28-fold reduction in potency compared to passage 3. Electron microscopy studies revealed that very few polyhedra were produced in an FP infected cell (<10 polyhedra per section) and in most cases these polyhedra contained no virions. A specific failure in the intranuclear nucleocapsid envelopment process in the FP infected cells, leading to the accumulation of naked nucleocapsids, was observed. Genomic restriction endonuclease digestion profiles of budded virus DNA from all passages did not indicate any large DNA insertions or deletions that are often associated with such FP phenotypes for the extensively studied Autographa californica nucleopolyhedrovirus and Galleria mellonella nucleopolyhedrovirus. Within an HaSNPV 25K FP gene homologue, a single base-pair insertion (an adenine residue) within a region of repetitive sequences (seven adenine residues) was identified in one plaque-purified HaSNPV FP mutant. Furthermore, the sequences obtained from individual clones of the 25K FP gene PCR products of a late passage revealed point mutations or single base-pair insertions occurring throughout the gene. The mechanism of FP mutation in HaSNPV is likely similar to that seen for Lymantria dispar nucleopolyhedrovirus, involving point mutations or small insertions/deletions of the 25K FP gene.


[Pathophysiology and strategy for small-for-size graft syndrome after living-donor liver transplantation].
Small-for-size (SFS) graft syndrome is an important problem after living-donor liver transplantation in adults. Hemodynamic change is thought to be the main cause of graft injury. Excessive portal flow is associated with hepatic sinusoidal injury, and reduction of portal flow improves postoperative liver function. Increased venous outflow due to hepatic venoplasty or reconstruction of the middle hepatic vein decrease the risk of graft congestion. However, the intragraft acute-phase response remains unclear. Recent studies have revealed that downregulation of heat shock protein (HSP) may account for SFS graft injury, and induction of HSP may prevent SFS syndrome. On the other hand, derangement in the regulation of liver regeneration is recognized as another important factor. Further investigation of the regulatory mechanisms of liver regeneration in SFS grafts may suggest a strategy for the prevention and treatment of SFS syndrome. Successful transplantation of marginal-size liver grafts would improve outcome for recipients and increase the margin of safety for living donors.


Axonal transport of fluorescent carbocyanine dyes allows mapping of peripheral nerve territories in gingiva.
Sensory innervation of gingival tissue can cause neurogenic inflammation that depends on the extent of the branching area of the peripheral nerve fibers. We designed the present study to determine whether single trigeminal axons branch to both the buccal and palatal gingiva of maxillary molars of adult rats. Accumulation via retrograde transport of DiI (red) or DiA (green) fluorescent carbocyanine dyes in neurons of trigeminal ganglia was evaluated 7 days after applying one dye to the buccal sulcus and the other to the palatal sulcus. Both dyes were absorbed through the junctional epithelium, and the two sites each labeled similar numbers and sizes of neurons in the lateral zone of the maxillary division (44% from buccal and 46% from palatal gingiva). Double-labeled neurons had the same size (32.5 +/- 6.70 microns, mean circumference +/- S.D.) and location as single-labeled neurons, and they were 9% of the total. This study shows that exogenous dyes can diffuse into mucosa and thereby allow in vivo mapping of sensory nerve branching patterns to several intact tissues per animal. We found that 9% of the labeled cells extended to both the buccal and palatal gingiva. Thus, inflammation that spreads from one gingival region to the other could have a neurogenic mechanism involving trigeminal sensory neurons that extend their peripheral branches to innervate both buccal and palatal gingiva of adult rat molars.


[Applications of polylactide and its copolymers in medical device fields].
Polylactide and its copolymers are a kind of biomedical material andhave been approved by U.S. Food and Drug Administration. This paper briefly introduces its applications in surgical suture, orthopedics, plastic surgery, ophthalmology and other medical device fields, and also analyzes its development in our country.


The effect of tricyclic antidepressants on cortex- and amygdala-kindled seizures in the rat.
The anticonvulsant effects of amitriptyline, imipramine, nortriptyline and desipramine were tested against focal and generalized seizures, triggered from either the amygdala or the cortex in fully kindled rats. Tests were administered on a 72- or a 24-hour schedule. Significant seizure suppression was achieved with only one drug, amitriptyline, and it occurred only at toxic or near-toxic doses. The differential, low-dose suppression of amygdala-kindled seizures, reported in earlier studies, was not seen in the present experiments. It may occur only in the short-interval test paradigms used by previous experimenters.


Detection of Epstein-Barr virus in posttransplantation T cell lymphoma in a kidney transplant recipient: case report and review.
Posttransplantation T cell lymphomas (PTTLs) are rather unusual, and their etiology remains unclear. We describe a case of Epstein-Barr virus (EBV)-associated small bowel T cell lymphoma in a patient 5 years after kidney transplantation. EBV was detected in a biopsy sample by in situ hybridization, immunohistochemical staining, and polymerase chain reaction analysis. Eight previously reported cases of EBV-associated PTTL are reviewed, in which special attention is paid to the methods used for assessing EBV. This case of EBV-associated PTTL is believed to be the most completely studied from the point of view of the methods used for detection of EBV. The prognosis of PTTL is poor, but it has been reported that therapeutic approaches can be successful if they are given early in the course of the illness. Therefore, it is necessary to improve the diagnosis PTTL and to assess the precise involvement of EBV in posttransplantation lymphoproliferative disorders.


Fast and Accurate Large-Scale Detection of β-Lactamase Genes Conferring Antibiotic Resistance.
Fast detection of β-lactamase (bla) genes allows improved surveillance studies and infection control measures, which can minimize the spread of antibiotic resistance. Although several molecular diagnostic methods have been developed to detect limited bla gene types, these methods have significant limitations, such as their failure to detect almost all clinically available bla genes. We developed a fast and accurate molecular method to overcome these limitations using 62 primer pairs, which were designed through elaborate optimization processes. To verify the ability of this large-scale bla detection method (large-scaleblaFinder), assays were performed on previously reported bacterial control isolates/strains. To confirm the applicability of the large-scaleblaFinder, the assays were performed on unreported clinical isolates. With perfect specificity and sensitivity in 189 control isolates/strains and 403 clinical isolates, the large-scaleblaFinder detected almost all clinically available bla genes. Notably, the large-scaleblaFinder detected 24 additional unreported bla genes in the isolates/strains that were previously studied, suggesting that previous methods detecting only limited types of bla genes can miss unexpected bla genes existing in pathogenic bacteria, and our method has the ability to detect almost all bla genes existing in a clinical isolate. The ability of large-scaleblaFinder to detect bla genes on a large scale enables prompt application to the detection of almost all bla genes present in bacterial pathogens. The widespread use of the large-scaleblaFinder in the future will provide an important aid for monitoring the emergence and dissemination of bla genes and minimizing the spread of resistant bacteria.


Alpha-adrenergic receptors in orthostatic hypotension syndromes.
Alpha-adrenergic receptor function was measured in platelets from patients with orthostatic hypotension and normotensive controls. Patients with idiopathic orthostatic hypotension (IOH) or multiple system atrophy (MSA) had more alpha-receptors than controls. Patients with IOH, but not MSA, produced less prostaglandin E1 (PGE1)-stimulated cyclic AMP (cAMP) than controls. Patients with sympathotonic orthostatic hypotension (SOH) were similar to controls in receptor number and cAMP production. The percent norepinephrine (NE) inhibition of PGE1-stimulated cAMP production was similar in patients and controls. An increase in alpha-receptor number may result from decreased peripheral NE secretion in IOH and MSA. Increased alpha-receptor number and decreased cAMP production, which accompany essential hypertension, may contribute to the supine hypertension of IOH, and an increase in alpha-receptor number may contribute to the supine hypertension of MSA. SOH patients appear to have no abnormalities of alpha-receptor function.


Microwave spectrum and conformational composition of 2-chloroethylisocyanide.
2-Chloroethylisocyanide (ClCH(2)CH(2)N≡C) has been synthesized, and its microwave spectrum has been investigated in the 20-97 GHz spectral region. The spectra of (35)Cl and (37)Cl isotopologues of two conformers have been assigned. The Cl-C-C-N chain of atoms is antiperiplanar in one of these rotamers and synclinal in the second. The energy difference between the two forms has been obtained from relative intensity measurements. It was found that the antiperiplanar conformer is favored over the synclinal form by 4.3(8) kJ/mol. Quantum chemical calculations at the CCSD/cc-pVTZ and B3LYP/cc-pVTZ levels of theory have been performed. Most, but not all, of the spectroscopic constants predicted in these calculations are in good agreement with their experimental counterparts. The theoretical calculations correctly predict that the 2-chloroethylisocyanide exists as a mixture of an antiperiplanar and a synclinal conformer, with the former about 3.5 kJ/mol more stable than the latter. Both methods of calculations find that the antiperiplanar rotamer has a symmetry plane. The dihedral angle formed by the Cl-C-C-N link of atoms of the synclinal form is 67° according to the CCSD calculations. It is estimated from a comparison with the experimental rotational constants that this dihedral angle is uncertain by ±3°.


Bone cement and wound healing. An experimental study in the rat.
The local effect of methyl methacrylate on wound healing was studied in rats using viscose cellulose sponges. A 7 mm diameter cylindrical section was removed from the sponges, filled with freshly prepared bone cement or left empty in controls. Two sponges were implanted subcutaneously into each rat. The concentrations of DNA, RNA-ribose, nitrogen, hydroxyproline, uronic acids and hexosamines of the sponges were determined 5, 10 and 21 days postoperatively. The concentrations of collagen and glycosaminoglycans were similar in experimental and control samples and only small differences were detected in the amounts of DNA. It was concluded that methyl methacrylate bone cement did not have any practical harmful effects on wound healing.


The neurobiology of human immunodeficiency virus infections.
A variety of diseases of the central and peripheral nervous systems evolves during the course of human immunodeficiency virus (HIV) infections. Most are not related to documented opportunistic infections and may be the direct result of HIV infections, as large proportions of healthy and ill HIV-infected persons show evidence of nervous system infection. These diseases occur at different times during the infection and have diverse inflammatory, demyelinating, or degenerative pathological features that suggest different pathogenetic mechanisms. The route and determinants of HIV invasion of the nervous system are unknown. Within the brain, viral antigen and RNA are found predominantly in macrophages, but the reason why profound dementia and cortical atrophy result from this infection remains a mystery. By analogy to other lentivirus infections, particularly visna virus in sheep, neuropathological changes may be mediated by cytokines. Other possible pathogenetic mechanisms include toxicity of viral polypeptides, transactivation of viral or cellular genes, autoimmunity, or other opportunistic infections. Clarification of the pathogenesis of HIV-related diseases is critical to the design of rational therapies.


Ex-post size control of high-temperature-stable yolk-shell Au, @ZrO(2) catalysts.
Yolk-shell catalysts have attracted interest in both academia and industry, since they combine high-temperature stability with a reduced complexity for kinetic and mechanistic investigations. This contribution presents a possibility to adjust the size of an active gold core inside a porous zirconia shell via an ex-post-modification approach.


Editorial for the Special Issue "Parasitic Diseases from Wild Animals with Emphasis on Zoonotic Infections".
The present Editorial intends to briefly describe the findings published in the Special Issue, "Parasitic diseases from wild animals with an emphasis on zoonotic infections". Prevalence data or diagnostic techniques were the focus of several zoonotic parasites transmitted from wildlife, including the protozoa Toxoplasma, Cryptosporidium, Giardia, Blastocystis and Leishmania, and the helminths Echinococcus and Anisakis.


Coding theory of visual pattern completion.
It is possible to construct a line drawing that represents one object partly hidden behind another, and most subjects complete the interrupted figure and see the hidden object as whole. This article is addressed to two problems: (a) What are the necessary and sufficient conditions for such figural completion to occur, and (b) exactly what will be seen behind the occluding figure---that is, what completion will be made? Leeuwenberg's coding model for line drawings was used to analyze a number of such figures, along with the hypothesis that figural completion occurs whenever it results in a simplification of final code of the whole figure. Data from previous experiments along with results from two new experimental studies were collected and shown to agree with this hypothesis. Of various possible figural completions or "mosaic" interpretations, subjects chose the ones resulting in the simplest overall code. However, the above conclusions are correct only if "simple" is precisely defined as the smallest information load in a completely reduced code. Other possible theories of figural completion, both structuralist and Gestalt, may invoke familiarity, particular "cues," like T-shaped intersections, simplicity of the hidden figure, symmetry, and good continuation. All such possibilities were considered in the experiments and shown to fail, wrongly predicting at least one figure. The coding-theory analysis, on the other hand, made correct predictions for all of the 25 figures used.


Ecological Exploration of Knowledge and Attitudes Towards Tobacco and E-Cigarettes Among Primary School Children, Teachers, and Parents in Wales: A Qualitative Study.
Experimentation with e-cigarettes has grown rapidly among UK adolescents. To date, this topic has been primarily researched in secondary schools, with less understanding of development of attitudes and behaviours at an earlier age. This research reports qualitative data from interviews with pupils, parents, and teachers at 4 case study schools in Wales (N = 42). It draws on Bronfenbrenner's Ecological Systems Theory to consider how the intersection of systems surrounding primary school-age children and their interaction with these systems, shape knowledge, and attitudes towards e-cigarettes and tobacco. Findings indicate that consistent messaging on smoking from school and family was reflected in strong disapproval among pupils and clear understanding of harms. This was less evident for e-cigarettes, where messages were mixed and inconsistent between home and school, with concerns over what to tell children about e-cigarettes in light of mixed messages and absence of official guidance. Implications of findings for policy and teaching are discussed.


N-acetylglucosaminyltransferase regulates the expression of neolactoglycolipids including sulfoglucuronylglycolipids in the developing nervous system.
Lactosylceramide N-acetylglucosaminyltransferase (GlcNac-Tr) in the synthesis of lactotriosylceramide (LcOse3Cer) was characterized in the nervous system. The microsomal membrane GlcNAc-Tr required a divalent metal ion, preferably Mn2+, and a nonionic detergent. The pH optimum was around 7.0. The enzyme also transferred GlcNAc to neolactotetraosylceramide (nLcOse4Cer), GM1, and asialo-GM1, but not to other glycolipids. The Km value for lactosylceramide was 21 microM (Vmax = 91 pmol/mg/h), and that for nLcOse4Cer was 35 microM (Vmax = 112 pmol/mg/h). The GlcNAc-Tr for the glycolipids appears to be separate from that for oligosaccharides. The developmental expression of GlcNAc-Tr, both in the cerebral cortex and cerebellum, correlated well with the tissue levels of LcOse3Cer, nLcOse4Cer, sulfoglucuronylglycolipids (SGGLs), and other neolacto series glycolipids (nLSGs). In the cerebral cortex, the specific activity of GlcNAc-Tr decreased sharply from a maximum level at embryonic day 15, and by postnatal day 10 onward, it was undetectable. In the adult cerebral cortex, although significant activities of other glycosyltransferases involved in the subsequent steps of the synthesis of SGGLs were present, the absence of GlcNAc-Tr stymied the formation of LcOse3Cer and therefore the synthesis of nLSGs, including SGGLs. In the cerebellum, the GlcNAc-Tr specific activity declined from the day of birth to postnatal day 3, but later, the activity increased and reached a maximum at postnatal day 15, which correlated with the increasing synthesis of nLSGs. The results indicate that lactosylceramide GlcNAc-Tr is the key regulatory enzyme controlling the differential expression of all nLSGs in the developing nervous system.


Comparison of systemic and local respiratory tract cellular immunity in the neonatal foal.
Blood neutrophils from 10 Thoroughbred and 2 Pony foals were evaluated using in-vitro cellular function tests of chemotaxis, chemiluminescence, phagocytosis and intracellular killing. A comparison of the functional capacities of these cells before and 2-4 days after the ingestion of colostrum indicated an improvement in blood neutrophil chemotaxis and chemiluminescence. Bronchopulmonary lavage was carried out on 9 Thoroughbred and 2 Pony 36-h-old foals. The technique used did not require sedation or anaesthesia. Pulmonary alveolar macrophages were the predominant cell type recovered. When comparisons were made between blood neutrophils and pulmonary alveolar macrophages in the same animal fewer pulmonary alveolar macrophages were phagocytic and there was little if any evidence of intracellular killing by pulmonary alveolar macrophages.


[Autotransplantation of islands of Langerhans in dogs].
Six dogs received intraportally an autograft of isolated non purified pancreatic islets after total pancreatectomy. The isolation was made by collagenase technique, using a quarter to a half of the total pancreatic mass. The results of different transplantation technics are discussed. We conclude the necessity of: 1) a good venous distension of the pancreas, 2) the use of at least a third of the pancreatic gland to prepare the islets, 3) a tissue reinjection the closest as possible of the portal vein.


The effect of temperature in the range 0-35 degrees C on the resting tension of frog's muscle.
1. It has long been known that a resting muscle shows a reversible ;rubber-like' response to a change of temperature: it develops tension when warmed and this reverses on cooling. It was recently shown (Hill, 1968) that part of the resting tension is due to a weak interaction between the sliding filaments, and it was suggested that the rubber-like tension might be caused by the same process rather than by some inert structural component. Further information on this point has now been obtained from some observations on the effect of temperature on isometric tension at temperatures not far below the level (28-35 degrees C) at which a heat contracture is produced.2. The temperature of a frog's sartorius was changed by moving it up and down in a vessel containing Ringer solution at two different temperatures. The temperature in one part was maintained constant in the range 0-20 degrees C and in the other at 5-35 degrees C. The changes was 90% complete in 12 sec.3. From 0 degrees up to about 23 degrees C the tension developed per 1 degrees C rise of temperature (DeltaP/DeltaT) is almost constant, but as the temperature approaches the level at which a heat contracture appears the value of DeltaP/DeltaT rises steeply. This behaviour indicates that the tension in question has an ;active' rather than a ;passive' origin, and this view is supported by other evidence from experiments with muscles in hypertonic solutions, described in the next paper.4. It was found that the temperature at which a muscle goes into a heat contracture depends on the length at which it is set; the critical temperature is lower in an extended muscle. A shortened muscle at a temperature not far below the critical value will therefore produce a contracture when it is stretched.


Geographic remoteness, area-level socioeconomic disadvantage and inequalities in colorectal cancer survival in Queensland: a multilevel analysis.
To explore the impact of geographical remoteness and area-level socioeconomic disadvantage on colorectal cancer (CRC) survival. Multilevel logistic regression and Markov chain Monte Carlo simulations were used to analyze geographical variations in five-year all-cause and CRC-specific survival across 478 regions in Queensland Australia for 22,727 CRC cases aged 20-84 years diagnosed from 1997-2007. Area-level disadvantage and geographic remoteness were independently associated with CRC survival. After full multivariate adjustment (both levels), patients from remote (odds Ratio [OR]: 1.24, 95%CrI: 1.07-1.42) and more disadvantaged quintiles (OR=1.12, 1.15, 1.20, 1.23 for Quintiles 4, 3, 2 and 1 respectively) had lower CRC-specific survival than major cities and least disadvantaged areas. Similar associations were found for all-cause survival. Area disadvantage accounted for a substantial amount of the all-cause variation between areas. We have demonstrated that the area-level inequalities in survival of colorectal cancer patients cannot be explained by the measured individual-level characteristics of the patients or their cancer and remain after adjusting for cancer stage. Further research is urgently needed to clarify the factors that underlie the survival differences, including the importance of geographical differences in clinical management of CRC.


A lifelong bleeding disorder associated with a deficiency of plasminogen activator inhibitor type 1.
A 36-year-old patient was investigated for a lifelong history of epistaxis and delayed bleeding after minor surgeries. Deficiencies or abnormalities of the coagulation system, of platelet function, or of factor XIII and alpha-2-antiplasmin were excluded. Consistently, however, over a period of 7 years, a high basal euglobulin fibrinolytic activity was observed that was characterized by a high tissue-type plasminogen activator (t-PA) activity, normal t-PA antigen, and undetectable plasminogen activator inhibitor type-1 (PAI-1) antigen and activity. The high specific activity of t-PA (640,000 IU/mg) and the minimal amounts of t-PA/PAI-1 complexes detected by fibrin zymography suggest that in this patient all t-PA was active. This is in striking contrast to normal plasma, where the majority of t-PA is complexed to PAI-1. Thus, in this patient, a severe deficiency of PAI-1 is associated with a delayed type bleeding tendency. Our observation underscores the importance of plasma PAI-1 for the stabilization of the hemostatic plug.


Establishment and characterization of Spodoptera littoralis cell line (SL 96), adapted at 19 degrees C permissive for different baculoviruses.
Cells from ovarioule tissues of the Egyptian cotton leaf worm, Spodoptera littoralis (SL 96) were established, identified and characterized comparing with other lepidopteran cell lines using isozymes, karyotyping, RAPD PCR, and polyacrylamide gel electrophoresis polypeptide PAGE profile. Comparison of the number of chromosomes and PAGE profiles; also the isozymes profiles demonstrate the possibility to distinguish the cell lines by those analyses and having a distinguishable finger print for every cell line. A complete replication of the S. littoralis granulovirus (SpliGV), nucleopolyherovirus (SpliNPV), and Phthorimaea operculella granulovirus (PhopGV) was obtained in vitro by both viral infection and DNA transfection in the S. littoralis (S196) cell line. Spli-GV and PhopGV multiplied extensively during several passages in S196 cells at 19 degrees C. Virus infected cells were incubated at 19 degrees C for the first 4 hours and then at .27 degrees C for the rest of the experiment (20 days). Generally, all the three viral multiplications proceeded at the same rate approximately. Comparison of Spli GV progenies multiplied either in vivo or in vitro, using electron microscopy and restriction profile analysis, showed their identity. Viral infections were detected also by specific prepared nucleic probes.