Investigational new drugs for the treatment of acute coronary syndrome.
Ischemic heart disease is the most common cause of death worldwide. Despite improvements in interventional and pharmacological therapy for acute coronary syndrome (ACS), the risk of recurrent myocardial ischemia and mortality early after ACS remains high. Our improved understanding of the increasing role of inflammation in the pathogenesis of ACS and its relationship to atherosclerotic plaque rupture and thrombosis has led to the development of more potent anti-thrombotic and novel anti-inflammatory therapies for the treatment of ACS. In this review, the authors explore: the developing pharmacotherapy in the field of cardiology for ACS; antiplatelet agents (both further development of classical modalities together with pioneering agents); evolving use of anticoagulation in its treatment, and exploration in the use of novel anti-inflammatories and biological agents. Data from trials involving the use of immunological and cellular-based treatments show promising results and herald further possible reduction in infarct burden in ACS alongside the possibility of recovery in cardiac function following infarction.


Crystal structures of four δ-keto esters and a Cambridge Structural Database analysis of cyano-halogen interactions.
The revived interest in halogen bonding as a tool in pharmaceutical cocrystals and drug design has indicated that cyano-halogen interactions could play an important role. The crystal structures of four closely related δ-keto esters, which differ only in the substitution at a single C atom (by H, OMe, Cl and Br), are compared, namely ethyl 2-cyano-5-oxo-5-phenyl-3-(piperidin-1-yl)pent-2-enoate, C19H22N2O3, (1), ethyl 2-cyano-5-(4-methoxyphenyl)-5-oxo-3-(piperidin-1-yl)pent-2-enoate, C20H24N2O4, (2), ethyl 5-(4-chlorophenyl)-2-cyano-5-oxo-3-(piperidin-1-yl)pent-2-enoate, C19H21ClN2O3, (3), and the previously published ethyl 5-(4-bromophenyl)-2-cyano-5-oxo-3-(piperidin-1-yl)pent-2-enoate, C19H21BrN2O3, (4) [Maurya, Vasudev & Gupta (2013). RSC Adv. 3, 12955-12962]. The molecular conformations are very similar, while there are differences in the molecular assemblies. Intermolecular C-H...O hydrogen bonds are found to be the primary interactions in the crystal packing and are present in all four structures. The halogenated derivatives have additional aromatic-aromatic interactions and cyano-halogen interactions, further stabilizing the molecular packing. A database analysis of cyano-halogen interactions using the Cambridge Structural Database [CSD; Groom & Allen (2014). Angew. Chem. Int. Ed. 53, 662-671] revealed that about 13% of the organic molecular crystals containing both cyano and halogen groups have cyano-halogen interactions in their packing. Three geometric parameters for the C-X...N[triple-bond]C interaction (X = F, Cl, Br or I), viz. the N...X distance and the C-X...N and C-N...X angles, were analysed. The results indicate that all the short cyano-halogen contacts in the CSD can be classified as halogen bonds, which are directional noncovalent interactions.


Manipulation of starch granule size distribution in potato tubers by modulation of plastid division.
Starch granule size is an important parameter for starch applications in industry. Starch granules are formed in amyloplasts, which are, like chloroplasts, derived from proplastids. Division processes and associated machinery are likely to be similar for all plastids. Essential roles for FtsZ proteins in plastid division in land plants have been revealed. FtsZ forms the so-called Z ring which, together with inner and outer plastid division rings, brings about constriction of the plastid. It has been shown that modulation of the expression level of FtsZ may result in altered chloroplast size and number. To test whether FtsZ is also involved in amyloplast division and whether this, in turn, may affect the starch granule size in crop plants, FtsZ protein levels were either reduced or increased in potato. As shown previously in other plant species, decreased StFtsZ1 protein levels in leaves resulted in a decrease in the number of chloroplasts in guard cells. More interestingly, plants with increased StFtsZ1 protein levels in tubers resulted in less, but larger, starch granules. This suggests that the stoichiometry between StFtsZ1 and other components of the plastid division machinery is important for its function. Starch from these tubers also had altered pasting properties and phosphate content. The importance of our results for the starch industry is discussed.


Restoring axonal localization and transport of transmembrane receptors to promote repair within the injured CNS: a critical step in CNS regeneration.
Each neuronal subtype is distinct in how it develops, responds to environmental cues, and whether it is capable of mounting a regenerative response following injury. Although the adult central nervous system (CNS) does not regenerate, several experimental interventions have been trialled with successful albeit limited instances of axonal repair. We highlight here some of these approaches including extracellular matrix (ECM) modification, cellular grafting, gene therapy-induced replacement of proteins, as well as application of biomaterials. We also review the recent report demonstrating the failure of axonal localization and transport of growth-promoting receptors within certain classes of mature neurons. More specifically, we discuss an inability of integrin receptors to localize within the axonal compartment of mature motor neurons such as in the corticospinal and rubrospinal tracts, whereas in immature neurons of those pathways and in mature sensory tracts such as in the optic nerve and dorsal column pathways these receptors readily localize within axons. Furthermore we assert that this failure of axonal localization contributes to the intrinsic inability of axonal regeneration. We conclude by highlighting the necessity for both combined therapies as well as a targeted approach specific to both age and neuronal subtype will be required to induce substantial CNS repair.


Local Estrogen Synthesis Regulates Parallel Fiber-Purkinje Cell Neurotransmission Within the Cerebellar Cortex.
Estrogens affect cerebellar activity and cerebellum-based behaviors. Within the adult rodent cerebellum, the best-characterized action of estradiol is to enhance glutamatergic signaling. However, the mechanisms by which estradiol promotes glutamatergic neurotransmission remain unknown. Within the mouse cerebellum, we found that estrogen receptor activation of metabotropic glutamate receptor type 1a strongly enhances neurotransmission at the parallel fiber-Purkinje cell synapse. The blockade of local estrogen synthesis within the cerebellum results in a diminution of glutamatergic neurotransmission. Correspondingly, decreased estrogen availability via gonadectomy or blockade of aromatase activity negatively affects locomotor performance. These data indicate that locally derived, and not just gonad-derived, estrogens affect cerebellar physiology and function. In addition, estrogens were found to facilitate parallel fiber-Purkinje cell synaptic transmission in both sexes. As such, the actions of estradiol to support cerebellar neurotransmission and cerebellum-based behaviors might be fundamental to understanding the normal processing of activity within the cerebellar cortex.


To Bond or Not to Bond: Metal-Metal Interaction in Heterobimetallic Rare-Earth Metal-Silver Complexes.
The reaction of 2,4-tBu2-6-(PPh2)PhOH (HOArP) with silver(I) triflate in a 3:1 molar ratio gave the mononuclear coinage metal complex (HOArP-κP)3AgIOTf (1). Treatment of HOArP with LnIII[N(SiMe3)2]3 (Ln = La, Sm, Y, Yb) in a 3:1 molar ratio yielded the mononuclear rare-earth metal complexes LnIII(OArP-κ2O,P)3 (2-Ln). The heterobimetallic rare-earth metal-silver complexes LnIII(OTf)(μ-OArP-1κ1O,2κ1P)3AgI (3-Ln) were prepared from monometallic precursors by reactions of equimolar amounts of 1 with LnIII[N(SiMe3)2]3 or 2-Ln with silver(I) triflate, respectively. The compounds were characterized by NMR, ultraviolet-visible (UV-vis), and infrared (IR) spectroscopy, single-crystal X-ray diffraction, elemental analysis, and the effective magnetic moments of the paramagnetic complexes were determined via the Evans NMR method. Computational studies were conducted on 3-La and 3-Y.


Implant fracture failure rate and potential associated risk indicators: An up to 12-year retrospective study of implants in 5,124 patients.
This study investigated fracture rates and risk indicators for fractures in internal connection dental implants. We performed a retrospective analysis of 19,006 internal connection implants used in fixed restoration in 5,124 patients (4,570 males, 554 females) at the Dental Hospital of Veterans Health Service Medical Center between 2006 and 2015. Patients were followed through June 2018 (0.03-12.39 years post-installation). Clinical factors (age, sex, implant diameter, implant length, placement site, bone graft, fixture material, cervical feature, abutment connection, microthread, and platform switching) were recorded. Kaplan-Meier survival analysis identified risk indicators associated with an implant fracture. Cox regression models elucidated potential fracture risks. One hundred and seventy-four implants fractured in 135 patients, for an incidence rate of 0.92% after an average of 4.95 ± 2.14 years of use. Kaplan-Meier estimates showed that the 3-, 5-, and 10-year survival rates of implants were 99.8%, 99.2%, and 97.7%, respectively. In the multivariable Cox regression model, the diameter, location, history of bone graft, and microthread presence were significantly correlated with implant fractures. Wide-diameter implants had a reduced fracture risk within 90 months, after which the diameter did not correlate with fractures. Implants placed in the anterior mandible had a lower fracture risk within 90 months; mandibular premolar implants corresponded with a lower risk after 90 months. Implants without a history of bone graft or microthreads were more likely to fracture throughout the follow-up time. These results elucidate risk indicators for implant fractures and facilitate their reduction in clinical practice.


[Is it Possible to Improve Results in the Conservative Treatment Strategy in Patients With Acute Coronary Syndrome?]
Almost 60% of patients with acute coronary syndrome (ACS) without ST segment elevation are not subjected to revascularization procedures. This review analyzes the reasons for the choice of the conservative tactics of patients with ACS. The possibilities of improving outcomes by using modern medicines. Particular attention is given to drugs that affect energy metabolism in cardiomyocytes ischemia and reperfusion, provides data on the effect of L-carnitine on the high-risk markers, and decrease the incidence of adverse outcomes in patients with ACS.


Controlling the sugar beet fly Pegomyia mixta Vill. with entomopathogenic nematodes.
Sugar beet, Beta vulgaris L. is a strategic crop of sugar industry in Egypt. It is threatened by several insect pests among most important of them is the beet fly Pegomyia mixta. This work deals with the biological control of this insect using four entomopathogenic nematodes (EPNs). The nematodes included Steinernema carpocapsae S2, Steinernema feltiae, Heterorhabditis bacteriophora (HB1-3) and Heterorhabditis bacteriophora S1. Daily mortality of larvae and pupae of P. mixta were recorded after treatment with serial concentrations (500, 1000, 2000 and 4000 infective juveniles (IJs)/ml) of each of four studied EPNs. In the laboratory all tested nematodes killed the larvae inside their mines in the sugar beet leaves and developed in their bodies in different extends. They also killed the insect pupae in the soil and developed in their bodies. Young larvae were more susceptible than old ones. New pupae were more susceptible than old ones. In the field a single spray of S. feltiae or H. bacteriophora caused 81.3 or 75.9% reduction in the larval population of the in sugar beet leaves.


Surface functionality as a means to impact polymer nanoparticle size and structure.
When polymeric nanoparticles (NPs) are formed by nanoprecipitation, which is a nucleation-growth process, the control over size requires changing the polymer concentration or solvent composition. Here, we demonstrate that the NP size can be controlled independent of polymer variables by introducing a polyelectrolyte (PE) in the aqueous phase. PEs that exhibit hydrogen bonding (H-bonding) yield a reduction in NP size, whereas PEs that do not possess this characteristic promote the formation of larger NPs. The observed effect can be attributed to the formation of a diffusional barrier around the NP in the form of a dense shell. This principle of controlling NP size is not limited to polymers and can also be employed in the production of lipid NPs.


Analysis of Thymocyte Migration, Cellular Interactions, and Activation by Multiphoton Fluorescence Microscopy of Live Thymic Slices.
Thymocytes migrate through discrete compartments within the thymus, engaging in cellular interactions essential for their differentiation into functional and self-tolerant T cells. Thus, understanding the temporal and spatial behavior of thymocytes within an intact thymic microenvironment is critical for elucidating processes governing T cell development. Towards this end, we describe methods for preparing thymic explant slices, in which the migration of thymocytes through three-dimensional space can be probed using time-lapse, multiphoton fluorescence microscopy. Thymocytes, enriched for developmental subsets of interest, are labeled with cytoplasmic fluorescent dyes, and seeded onto live thymic slices that express an endogenous, stromal cell-specific fluorescent reporter. In response to chemotactic cues produced by thymic stromal cells, the labeled thymocytes migrate withinthymic microenvironments and engage in cellular interactions that recapitulate a physiological system, whichcan be readily imaged. Here we describe specimen preparation that maintains the integrity of thymic structures. We also describe imaging protocols for acquiring multiple fluorochrome channels to enable detection of thymocyte:stromal cell interactions and quantification of relative intracellular calcium levels to monitor T cell receptor activation. Parameters for quantifying motility and interaction behaviors during data analysis are also briefly described. The thymic slice is a versatile tool for probing live cell behaviors and developing novel hypotheses not readily apparent by static experimental methods.


Adolescent definitions of change in smoking behavior: an investigation.
Although adolescent smoking cessation has received increased research attention, little information exists as to how adolescents define change efforts for smoking behaviors. This issue is of particular importance because surveys routinely incorporate items assessing smoking cessation, yet how adolescents interpret such items is unclear. The present study investigated definitions of smoking behavior change efforts among adolescents. A total of 94 adolescent smokers-of average age 16.7 years (SD = 1.0), 56% female, and 71% White-were asked to define the terms quit, stop, and cut down smoking. Responses to the three questions were categorized using content analysis. Definitions of quit and stop were categorized as (a) stop permanently, (b) stop temporarily, (c) stop except in certain situations, and (d) reduce smoking (for quit only). Definitions of cut down were categorized as (a) reduce the number of cigarettes, (b) smoke less in a time frame, (c) reduce smoking occasions, and (d) smoke less. Three trained raters sorted responses into each of the categories. Definitions of quit and stop were most frequently categorized in the stop permanently category (86% and 75%, respectively). Definitions of cut down were distributed across categories, with 51% categorized as smoke less, 25% smoking less in a time frame, and 25% reducing number of cigarettes. Different definitions of stop were related to smoking history and motivation to quit, although the other two terms were not related to adolescent individual characteristics. Findings highlight the importance of using clearly defined questionnaire items when assessing adolescent smoking change efforts.


Self-inflicted enucleation of an eye: two case reports.
There are a number of reports of self-inflicted enucleation of the eye which indicate that this act probably protects the patients from guilt. It appears that religious delusions play a dominant role irrespective of primary diagnosis. Hence, enucleation of an eye may occur in various psychotic syndromes with religious delusions. In this report the history of two patients are presented to suggest that self-enucleation of the eye served as a protection from suicide. The management of these patients includes rapid neuroleptization and a close follow-up with both drug and psychological therapies.


Attention deficit/hyperactivity disorder symptoms and depression symptoms as mediators in the intergenerational transmission of smoking.
Attention deficit/hyperactivity disorder and depression have been found to be comorbid with smoking behaviors, and all three behavioral syndromes have been shown to be familially transmitted. The present paper reports on the results of analyses testing whether child attention deficit/hyperactivity disorder and depression symptoms were mediators in the intergenerational transmission of cigarette smoking. Path analyses using bootstrapped mediation procedures were conducted on data from a community sample of 764 families (one or both parents and one adolescent offspring) from the Indiana University Smoking Survey. Parents reported on their smoking behaviors, ADHD, and depression and their child's ADHD, while offspring reported on their smoking behaviors and depression. Although fathers' and mothers' smoking status, depression, and ADHD were not significantly correlated with boys' smoking initiation, there was a significant mediated (indirect) pathway from mothers' depression to boys' smoking initiation through boys' depression. Several parental variables were significantly correlated with smoking initiation in girls, and the pathways from mothers' smoking status, mothers' ADHD, and fathers' smoking status to girls' smoking initiation were significantly mediated by girls' ADHD. For adolescent girls, the intergenerational transmission of ADHD appears to be important in understanding the intergenerational transmission of cigarette smoking. Sex differences in the intergenerational transmission of psychopathology as it leads to smoking initiation were also discussed.


The effect of supervised exercises on static and dynamic balance in Parkinson's disease patients.
The aim of the this study was to examine the effects of supervised exercises on measures of static and dynamic balance Parkinson's disease (PD) patients. The study used a before-after study design. Seventeen PD patients with mild and moderate levels of disability were enrolled in the study. Patients followed an exercise program under a physiotherapist's supervision one day a week for 12 weeks. The standard Balance Master protocol was used before and after exercise to assess static and dynamic balance. A statistically significant difference was observed in the unilateral balance test, one of the static balance assessments performed while standing on the left or right leg with eyes closed (p < 0.05). With respect to dynamic balance, a statistically significant difference in the maximum excursion of limits of stability (LOS), one of the balance tests used in the supervised exercise programs for patient with Parkinson's disease, between measurements taken before and after exercises was also detected (p < 0.05). The change of LOS revealed that dynamic balance improved due to the exercises. Thus, our supervised exercise program provided improvement in dynamic balance of PD patients.


Leukocytoclastic vasculitis resolution with topical dapsone.
Leukocytoclastic vasculitis (LCV) is a disease characterized by inflammation of small vessels presenting with petechiae and palpable purpura. Leukocytoclastic vasculitis often spontaneously resolves within weeks and requires only symptomatic treatment. Chronic or severe disease can require systemic treatment with agents such as colchicine, dapsone, or corticosteroids, which are effective but carry a risk for serious adverse events. These side effects and/or medical contraindications preclude some patients from taking systemic medications for LCV. We present a case of biopsy-proven LCV in a 60-year-old woman that resolved after treatment with topical dapsone. Systemic dapsone is effective at treating LCV but requires screening for glucose-6-phosphate dehydrogenase deficiency and routine monitoring of blood counts, and its possible adverse effects include neuropathy, blood dyscrasia, and hypersensitivity syndrome. Topical dapsone may provide similar efficacy with far fewer adverse effects. Given this drug's favorable side-effect profile compared to the currently available alternatives, we believe it is a reasonable option in selected patients.


Casopitant, a neurokinin-1 receptor antagonist with anti-emetic and anti-nausea activities.
Casopitant, an inhibitor of the neurokinin-1 receptor, and its mesylate salt, are being developed by GlaxoSmithKline plc for the potential treatment of chemotherapy-induced nausea and vomiting (CINV), post-operative nausea and vomiting (PONV), as well as for anxiety, depression and insomnia. Phase II trials are ongoing for anxiety, depression and insomnia, and further results are awaited from phase III trials of CINV and PONV. At the time of publication, it was expected that applications to the FDA for regulatory approval for CINV and PONV would be filed in 2008. Casopitant was previously being developed for the treatment of overactive bladder; however, in September 2007, this indication was no longer listed on the company's product pipeline.


Emergency treatment of urethral obstruction in male cats.
Cats with mild urethral obstruction are anesthetized, the obstruction removed and the bladder lavaged. Moderately affected cats are sedated and given IV fluids, and usually return to normal soon after the obstruction is removed. Severely affected cats are given IV fluids, NaHCO3 and Ca gluconate, sedated or anesthetized and unblocked. Fluid administration is continued to avoid renal failure. The bladder can be expressed 3-4 times daily or bethanechol given to aid recovery of detrusor muscle function. Halothane, 1% thiopental or thiamylal, or ketamine-acepromazine can be used to anesthetize blocked cats. An 18- or 20-ga, 2 1/2-inch over-the-needle catheter or a lacrimal needle is used to relieve the obstruction, after which a 3 1/2-Fr Silastic or vinyl catheter is used for catheterization and bladder lavage with sterile saline. Cystotomy allows recuperation before definitive corrective surgery.


A new regression-based method for the eye blinks artifacts correction in the EEG signal, without using any EOG channel.
Eye blinks artifacts correction in the EEG signal is a best practice in many applications. Nowadays, different approaches can be used to overcome such an issue: the most used methods are based on regression techniques and Independent Component Analysis. It is not clear which is the best performing method, thus the choice of which method to adopt depends on the specific application, on the basis of the method limitations. In fact, on one hand the regression-based methods require at least one EOG channel, and are affected by the mutual contamination between EEG and EOG signals. On the other hand, the ICA-based methods need a higher number of electrodes and a greater computational effort than the regression-based ones. In this study, a new regression-based method has been proposed and compared with three of the most used algorithms (Gratton, extended InfoMax, SOBI) for eye blinks correction. The results showed that the proposed algorithm was able (i) to achieve similar efficiency of the other methods in correcting the blinks, but without requiring neither EOG channels, nor a great electrodes number, nor a high computational effort, and (ii) to preserve EEG information in blink-free signal segments.


Modifiable risk factors for developing diabetes among women with previous gestational diabetes.
Gestational diabetes mellitus (GDM) affects approximately 2% to 4% of all pregnant women in the United States each year. Women who have had GDM are at high risk for developing nongestational diabetes. The objective of this study was to assess the prevalence of modifiable risk factors for developing diabetes among women with previous GDM only. Cross-sectional data for nonpregnant women from the 2003 Behavioral Risk Factor Surveillance System were used to estimate and compare the prevalence of modifiable risk factors among three groups: nonpregnant women with previous GDM only, nonpregnant women with current diabetes, and nonpregnant women without diabetes. In 2003, 7.6% of nonpregnant women aged 18 years and older in the United States had current self-reported physician-diagnosed diabetes, and 1.5% had previous GDM only. Compared with women without diabetes, women with previous GDM only had higher prevalence of no leisure-time physical activity (32.0% vs 25.7%), overweight (62.2% vs 49.0%), and obesity (29.4% vs 20.0%). After adjusting for sociodemographic variables, women with previous GDM only were more likely to have no leisure-time physical activity (prevalence odds ratio [POR], 1.4; 95% confidence interval [CI], 1.2-1.7) and more likely to be overweight (POR, 1.8; 95% CI, 1.6-2.2) or obese (POR, 1.7; 95% CI, 1.4-2.1), compared with women with no diabetes. Women with previous GDM are more likely to have modifiable risk factors for developing diabetes than women without diabetes. More attention to this issue is needed from health care providers and public health officials to encourage the promotion of healthy lifestyles during and after pregnancy.


Ultrasound measures of tendon thickness: Intra-rater, Inter-rater and Inter-machine reliability.
Ultrasound imaging is often used by physiotherapists and other healthcare professionals but the reliability of image acquisition with different ultrasound machines is unknown. The objective was to compare the intra-rater, inter-rater and intermachine reliability of thickness measurements of the plantar fascia (PF), Achilles tendon (AT), patellar tendon (PT) and elbow common extensor tendon (ECET) with musculoskeletal ultrasound imaging (MSUS). Tendon thickness was measured in four anatomical structures (14 participants, 28 images per tendon) by two sonographers and with two different ultrasound machines. Intraclass Correlation Coefficients (ICCs) and Bland-Altman plots were calculated. The standard error of measurement (SEM) and minimum detectable difference (MDD) were calculated. Inter-rater reliability was excellent for AT (ICC=0.98; 95% CI= 0.96-0.99) and very good for PT (ICC=0.85; 95% CI = 0.67-0.93) and ECET (ICC=0.81; 95% CI= 0.72-0.94). Reliability for PF was moderate, with an ICC of 0.63 (CI 95%= 0.20-0.83). Bland-Altman plot for inter-machine reliability showed a mean difference of 1 m for PF measurements and a mean difference of 4 m and 20 m for AT and PT. The relative SEMs were below 7% and the MDCs were below 0.7 mm. The MSUS reliability in measuring thickness of the four tendons is confirmed by the homogeneous readings intra sonographers, between operators and between different machines. Level of evidence: Tendon thickness can be measured reliably on different ultrasound devices, which is an important step forward in the use of this technique in daily clinical practice and research. III.


Prevalence of total daily walking among US adults, 2002-2003.
Walking for exercise is a popular leisure-time activity pursuit among US adults; however, little information is available about total daily walking. A nationally representative random sample of 10,461 US adults (4,438 men and 6,023 women) was surveyed via telephone between 2002 and 2003. Weekly frequency and daily duration of walking for all purposes in bouts of at least 10 min were measured. Regular walking was defined as walking > or =5 d/wk, > or =30 min/d. Overall, 49% of adults (51% of men and 47% of women) were regular walkers, and approximately 17% reported no walking. Regular walking was significantly higher in employed adults and decreased with increasing age in women and body mass index in both sexes. Total walking was significantly higher among adults with lower levels of educational attainment and did not vary significantly by race/ethnicity. These results affirm the popularity of walking in the United States.


How do location and control over the music influence listeners' responses?
This study uses Mehrabian and Russell's () Pleasure-Arousal-Dominance (PAD) model to consider how responses to both the music heard and overall in-situ listening experience are influenced by the listener's degree of control over music selected for a particular listening episode and the location in which the listening takes place. Following recruitment via campus advertisements and a university research participation program, 216 individuals completed a background questionnaire and music listening task in a 3 (location) × 2 (experimenter- or participant-selected music) design. After the listening task, participants completed a short questionnaire concerning the music they heard and the overall in-situ listening experience. Results demonstrated that there was a positive relationship between control and liking for the music and episode, whether the former was considered in terms of: (1) whether the music was self-selected or experimenter-selected or (2) overt ratings of perceived control. Furthermore, the location and liking for the music were related to people's judgments of their enjoyment of the overall experience. This research indicates that the PAD model is a useful framework for understanding everyday music listening and supports the contention that, in a musical context, dominance may be operationalized as control over the music.


Concentration of lactoferrin in milk of normal lactating cows and changes occurring during mastitis.
The mean lactoferrin (Lf) concentration determined by electroimmunodiffusion (EID) assay of whey preparations from 80 quarters of 20 normal lactating cows was 0.35 mg/ml. The mean alpha-lactalbumin (alpha-LAC) and bovine serum albumin (BSA) concentrations were 2.01 mg/ml and 0.29 mg/ml, respectively. The mean was significantly related to cell count (P smaller than 0.01), BSA (P smaller than 0.05), stage of lactation (P smaller than 0.05), and milk production (P smaller than 0.05). The Lf-milk production relationship was the only negative correlation. In 11 cows with mastitis, there was a significant (P smaller than 0.01) increase in mean Lf concentration in infected quarters from 0.55 mg/ml on day 1 of the infection to 1.89 mg/ml by day 3. By day 15 clinical signs had subsided and mean Lf concentrations had decreased to near day 1 values. On day 3 quarters infected with coliform bacteria (clinical mastitis generally more severe) had mean Lf values more than twofold greater than those quarters infected with species of Staphylococcus or Streptococcus (milder clinical signs). Noninfected (control) quarters of cows having coliform bacteria-infected quarters had slightly increased mean Lf concentrations, where Lf concentration in contral quarters of cows having quarters infected with gram-positive organisms remained unchanged.


Integrative pan-cancer landscape of MMS22L and its potential role in hepatocellular carcinoma.
Methyl methanesulfonate-sensitivity protein 22-like (MMS22L) is crucial in protecting genome integrity during DNA replication by preventing DNA damage and maintaining efficient homologous recombination. However, the role of MMS22L in human cancers remains unclear. Here, we reported the landscape of MMS22L using multi-omics data and identified the relationship between the MMS22L status and pan-cancer prognosis. In addition, the correlation of MMS22L mRNA expression levels with tumor mutational burden, microsatellite instability, homologous recombination deficiency, and loss of heterozygosity in pan-cancer was also described in this study. Furthermore, this study was the first to characterize the relationship between mRNA expression of MMS22L and immune cell infiltration in the tumor microenvironment in human cancer. Concurrently, this study explored the crucial role of MMS22L in different immunotherapy cohorts through current immunotherapy experiments. Eventually, we investigated the role of MMS22L in hepatocellular carcinoma (HCC). The results demonstrated that MMS22L is widely expressed in multiple HCC cell lines, and our results emphasized that MMS22L was involved in HCC progression and affects the prognosis of patients with HCC through multiple independent validation cohorts. Collectively, our findings reveal the essential role of MMS22L as a tumor-regulating gene in human cancers while further emphasizing its feasibility as a novel molecular marker in HCC. These findings provide an essential reference for the study of MMS22L in tumors.


Task phase-specific involvement of the rat posterior parietal cortex in performance of the TUNL task.
The posterior parietal cortex (PPC) participates in cognitive processes including working memory (WM), sensory evidence accumulation, and perceptually guided decision making. However, surprisingly little work has used temporally precise manipulations to dissect its role in different epochs of behavior taking place over short timespans, such as WM tasks. As a result, a consistent view of the temporally precise role of the PPC in these processes has not been described. In the present study, we investigated the temporally specific role of the PPC in the Trial-Unique, Nonmatching-to-Location (TUNL) task, a touchscreen-based, visuospatial WM task that relies on the PPC. To disrupt PPC activity in a temporally precise manner, we applied mild intracranial electrical stimulation (ICES). We found that intra-PPC ICES (100 μA) significantly impaired accuracy in TUNL without significantly altering response latency. Moreover, we found that the impairment was specific to ICES applied during the delay and test phases of TUNL. Consistent with previous reports showing delay- and choice-specific neuronal activity in the PPC, the results provide evidence that the rat PPC is required for maintaining memory representations of stimuli over a delay period as well as for making successful comparisons and choices between test stimuli. In contrast, the PPC appears not to be critical for initial encoding of sample stimuli. This pattern of results may indicate that early encoding of visual stimuli is independent of the PPC or that the PPC becomes engaged only when visual stimuli are spatially complex or involve memory or decision making.


Analysis of Endophytic Bacterial Communities of Potato by Plating and Denaturing Gradient Gel Electrophoresis (DGGE) of 16S rDNA Based PCR Fragments.
The diversity of endophytic bacterial populations of potato (Solanum tuberosum cv Desirée) was assessed using a combination of dilution plating of plant macerates followed by isolation and characterization of isolates, and direct PCR-DGGE on the basis of DNA extracted from plants. The culturable endophytic bacterial communities detected in potato stem bases as well as in roots were in most cases on the order 103 to 105 CFU g?1 of fresh plant tissue. Dilution plating revealed that a range of bacterial types dominated these populations. Dominant isolates fell into the a and g subgroups of the Proteobacteria, as well as in the Flavobacterium/Cytophaga group. Different representatives of the Firmicutes were also found. The most frequently isolated strains (>5% of the total) were characterized as different Pseudomonas spp. (including P. aureofaciens, P. corrugata, and P. putida), Agrobacterium radiobacter, Stenotrophomonas maltophilia, and Flavobacterium resinovorans, using fatty acid methyl ester (FAME) analysis and/or sequencing of their partial 16S ribosomal RNA genes. Other Proteobacteria or Firmicutes were also found, albeit infrequently, and mainly in potato stem tissue. The fate of three putative potato endophytes, Stenotrophomonas maltophilia, Bacillus sp., and Sphingomonas paucimobilis, was monitored following their release into potato plants via injection, via root dipping, or via the soil. Following stem injection, the S. maltophilia and Bacillus inoculants could be tracked over time periods of, respectively, 22 and 1 day(s) by dilution plating as well as via PCR-DGGE. However, only S. maltophilia was able to colonize, and persist in, plant tissue from soil or dipped roots. S. paucimobilis was never recovered from the plant irrespective of the mode of introduction. The diversity of the indigenous bacterial flora associated with potato was then monitored via PCR-DGGE. The patterns obtained revealed the existence of bacterial communities of limited complexity, with communities from potato stems typically differing from those from stem peel and roots. Evidence was obtained for the endophytic occurrence of a range of organisms falling into the a, b, and g subgroups of the Proteobacteria as well as in the Firmicutes. Several of the sequences found matched those from isolates, suggesting that the molecular evidence reported culturable organisms. However, a number of sequences did not have matching sequences from isolates, suggesting that non-culturable or as-yet-uncultured endophytic organisms were being detected.


Influence of the freezing technique (nitrogen liquid vs ultrafreezer of -152 degrees C) and male-to-male variation over the semen quality in Canarian Mastiff breed dogs.
This study was carried out to assess the in vitro quality of canine semen frozen in an ultrafreezer at -152 degrees C and to evaluate the male-to-male variation of frozen semen in five male dogs of the Canarian Mastiff breed. Four ejaculates of each dog were processed individually (5% glycerol and 0.5% Equex) to reach a final concentration of 100 x 10(6) spermatozoa/ml. Then, two freezing techniques were tested to assess the seminal quality (sperm motility, live spermatozoa and abnormal sperm cell percentages) at 1, 30, 60, 120 and 360 days after freezing: (i) semen was frozen and stored in liquid nitrogen; (ii) semen was frozen and stored in the ultrafreezer at -152 degrees C. After freezing-thawing, both freezing protocols showed no significant differences in sperm motility and the percentages of live and abnormal spermatozoa. On the other hand, the microscopic characteristics of spermatozoa in fresh semen were practically similar among males; however, after the semen processing and freezing, significant differences were observed (p < 0.05) among males, especially as regards sperm motility. This inter-individual variability was detected in both freezing protocols, showing that the male-to-male variation in the seminal quality post-freezing was independent of the freezing technique used. The in vitro results obtained in the Canarian Mastiff breed confirmed that the use of ultra-freezers at -152 degrees C is a potential alternative to liquid nitrogen for storing canine semen for long periods of time.


Discovering the Higgs bosons of minimal supersymmetry with muons and a bottom quark.
We investigate the prospects for the discovery at the CERN Large Hadron Collider (LHC) of a neutral Higgs boson produced with one bottom quark followed by Higgs decay into a muon pair. We work within the framework of the minimal supersymmetric model. The dominant physics background from the production of b mu(+)mu(-), j mu(+)mu(-), j=g,u,d,s,c, and bbW+W- is calculated with realistic acceptance cuts. Promising results are found for the CP-odd pseudoscalar (A0) and the heavier CP-even scalar (H0) Higgs bosons with masses up to 600 GeV. This discovery channel with one energetic bottom quark greatly improves the discovery potential of the LHC beyond the inclusive channel pp-->phi(0)-->mu(+)mu(-)+X.


Minimizing the learning curve for robotic-assisted radical cystectomy A single-surgeon, retrospective, cohort study.
Studies published to date have suggested non-inferiority of robotic-assisted radical cystectomy (RARC) compared to open radical cystectomy (ORC), while few centers in Canada have adopted this approach. Though multifactorial, the learning curve and operative time are often discussed barriers. Herein, we present outcomes from the largest Canadian cohort of RARC performed to date. We conducted a retrospective chart review of all patients undergoing RARC by a single surgeon with greater than 1500 robot-assisted radical prostatectomy (RARP) experience at our institution from May 2020 to December 2021. Clinicopathological, intraoperative, and postoperative data, as well as complications in the first 90 days, were collected. Regression analysis was used to determine the relationship between case volume and operative time/lymph node yield. A total of 31 patients underwent RARC during the study period, 26 of which were male. The median length of stay was six days (Q1-Q3 5-10), while days alive and out of hospital at 90 days were 83 days (Q1-Q3 80-85). Soft tissue margins were positive in 9.6% (3/31) of patients. Median lymph node yield was 17.0 lymph nodes (Q1-Q3 11-23). Median operative time was 241 minutes (Q1-Q3 228-252) in the ileal conduit group and 320 minutes (Q1-Q3 302-337) in the neobladder group. We observed four Clavien-Dindo grade >3 complications. The 90-day readmission rate and mortality rate were 17.2% (5) and 0% (0), respectively. There was no correlation between case volume and any outcome variables. Previous high-volume experience performing RARP reduces the learning curve for performing RARC, with similar short-term outcomes to high-volume centers.


Mosquito gonotrophic cycle and multiple feeding potential: contrasts between Anopheles and Aedes (Diptera: Culicidae).
Two aedine and three anopheline species were allowed to blood-feed to repletion, and their host-seeking behavior was measured with an olfactometer at intervals afterward. Both Aedes aegypti (L.) and Ae. albopictus (Skuse) were inhibited from subsequently seeking a host during the gonotrophic cycle, but Anopheles gambiae Giles, An. albimanus Wiedemann, and An. freeborni Aitken, all showed varying degrees of host-seeking behavior while their eggs matured. Continued host-seeking by some anophelines during the gonotrophic cycle has important implications for some assumptions commonly made about mosquito behavior and parasite transmission.


CCAAT/enhancer-binding protein delta gene expression is mediated by APRF/STAT3.
The CCAAT/enhancer-binding protein delta (C/EBP delta) transcription factor is known to be rarely expressed but sharply induced at an early stage of the acute phase response. To investigate the regulation mechanisms for this induction, the 5'-flanking region of the rat C/EBP delta gene was isolated. Functional analyses involving transfection and footprinting indicated that the upstream region up to - 175 bp is sufficient for the full basal activity in rat fibroblast 3Y1 cells. At least three cis-elements including a GC box are involved in this activity. When HepG2 cells were treated with interleukin-6 (IL-6), C/EBP delta mRNA was rapidly induced. Transfection and gel shift analyses identified the binding site for the acute phase response factor/signal transducers and activators of transcription (APRF/STAT3). These findings strongly indicate that C/EBP delta gene expression is mediated by APRF/STAT3, which is phosphorylated for the activation through the IL-6 receptor when cells are treated with IL-6, and trans-activates the other acute phase response genes.


Trypanosome RNA Editing Mediator Complex proteins have distinct functions in gRNA utilization.
Uridine insertion/deletion RNA editing is an essential process in kinetoplastid parasites whereby mitochondrial mRNAs are modified through the specific insertion and deletion of uridines to generate functional open reading frames, many of which encode components of the mitochondrial respiratory chain. The roles of numerous non-enzymatic editing factors have remained opaque given the limitations of conventional methods to interrogate the order and mechanism by which editing progresses and thus roles of individual proteins. Here, we examined whole populations of partially edited sequences using high throughput sequencing and a novel bioinformatic platform, the Trypanosome RNA Editing Alignment Tool (TREAT), to elucidate the roles of three proteins in the RNA Editing Mediator Complex (REMC). We determined that the factors examined function in the progression of editing through a gRNA; however, they have distinct roles and REMC is likely heterogeneous in composition. We provide the first evidence that editing can proceed through numerous paths within a single gRNA and that non-linear modifications are essential, generating commonly observed junction regions. Our data support a model in which RNA editing is executed via multiple paths that necessitate successive re-modification of junction regions facilitated, in part, by the REMC variant containing TbRGG2 and MRB8180.


Fluorescein angiographic evaluation of the effect of latanoprost treatment on blood-retinal barrier integrity: a review of studies conducted on pseudophakic glaucoma patients and on phakic and aphakic monkeys.
Endogenous prostaglandins (PGs) have been claimed to play a role in the development of cystoid macular edema (CME). Two fluorescein angiographic studies evaluating the effect of latanoprost, a new ocular hypotensive PG analogue, on blood-retinal barrier integrity are, therefore, reviewed here. In the first study, six of eight unilaterally aphakic cynomolgus monkeys were treated bilaterally once daily for six months with 0.035% latanoprost (seven times the clinically used oculohypotensive concentration). Two of the animals served as controls. Fluorescein angiography of the fundus after one, three and six months of treatment revealed no leakage of fluorescein in any of the 16 eyes. In another study, pseudophakic eyes of 16 glaucoma patients who received twice-daily treatment with 0.006% latanoprost for four weeks were compared to eight patients treated with placebo. Biomicroscopic examination did not reveal any signs of CME and only one placebo-treated eye revealed a slight perifoveal leakage of fluorescein. These studies suggest that topically-applied latanoprost does not have a fluorescein angiographically detectable direct effect on the integrity of the blood-retinal barrier system in phakic or aphakic monkey eyes or in pseudophakic human eyes. This does not rule out the occurrence of CME in eyes more susceptible to CME, due to vitreous loss, posterior capsulotomy, or other postoperative situations. Especially in those eyes a study with latanoprost is proposed. Since, fluorescein angiography is a rather crude method of detecting abnormalities of the blood-retinal barriers, vitreous fluorometry in addition is suggested.


Predicting hospital-associated mortality for Medicare patients. A method for patients with stroke, pneumonia, acute myocardial infarction, and congestive heart failure.
We created a microcomputer-based system that uses characteristics of the patient at admission to predict death within 30 days of hospital admission for Medicare patients with stroke, pneumonia, myocardial infarction, and congestive heart failure. These conditions account for 13% of discharges and 31% of 30-day mortality for Medicare patients over 64 years of age. The system was calibrated on a stratified, random sample of 5888 discharges (about 1470 for each condition) from seven states, with stratification by hospital type to make the sample nationally representative. The predictors must be specially abstracted from the medical record. The cross-validated R2 for predictions is 0.14 to 0.25, which is better than the values for other systems for which we have data. Risk-adjusted predicted group mortality rates may be useful in interpreting information on unadjusted mortality rates, and patient-specific predictions may be useful in identifying unexpected deaths for clinical review.


Thymocyte activating factor(s) in human gingival fluids.
Human gingival fluid contains a low-molecular-weight factor (10,000 to 25,000) which enhances the proliferation of murine thymocytes in the presence of suboptimal doses of mitogen. Although the gingival fluid has no Interleukin 2 (T cell growth factor) activity, as indicated by its inability to induce proliferation of an IL 2 dependent lymphocytic cell line, it is directly mitogenic for dermal fibroblasts. These studies suggest that the thymocyte and fibroblast growth-promoting properties of human gingival fluid may have important functions in regulating inflammatory responses in the human periodontal tissues.


Multiresponsive Tetra-Arylethene-Based Fluorescent Switch with Multicolored Changes: Single-Crystal Photochromism, Mechanochromism, and Acidichromism.
In this article, we report a simple tetra-arylethene-based fluorescent switch TPS═C4 modified with a flexible alkyl chain by the Schiff base structure. The incorporation of C═N retains the excellent photochromic property of tetra-arylethene and endows TPS═C4 with new multiresponsiveness of mechanochromism and acidichromism and multicolor changes. TPS═C4 shows remarkable mechanochromism from a deep blue emission at 420 nm to bright blue with a new shoulder band at 450 nm, which arises from the force-induced phase transition from the crystal state to an amorphous form. Both the original crystalline powder and the ground amorphous sample exhibit interesting acidichromism, and their emission colors turn yellow (530 nm), due to the protonation of C═N. More interestingly, TPS═C4 displays fascinating photochromism in multiple states, especially in the single-crystal state. The flexible alkyl chain offers enough free space for molecular motion and facilitates single-crystal photochromism. Due to the multiresponsiveness and multicolor switch, TPS═C4 can be satisfactorily used for the multidimensional anticounterfeiting application. To the best of our knowledge, TPS═C4 is a rare multifunctional molecule with a simple structure but featuring multiresponsiveness and multicolor switch.


The Sinorhizobium meliloti LysR family transcriptional factor LsrB is involved in regulation of glutathione biosynthesis.
Glutathione, a key antioxidant in Sinorhizobium meliloti, is required for the development of alfalfa (Medicago sativa) nitrogen-fixing nodules. This tripeptide can be synthesized by both γ-glutamyl cysteine synthetase (GshA) and glutathione synthetase (GshB) in Escherichia coli and S. meliloti. Genetic evidence has indicated that the null mutant of S. meliloti gshA or gshB1 does not establish efficient symbiosis on alfalfa. However, the transcriptional regulation of gshA and gshB has not been well understood. Here, S. meliloti LsrB, a member of LysR family transcriptional factors, was found to positively regulate glutathione biosynthesis by activating the transcription of gshA and gshB1 under both free-living and symbiotic conditions. The decrease in glutathione production in the lsrB in-frame deletion mutant (lsrB1-2) was determined by using quadrupole time-of-flight liquid chromatography-mass spectrometry. The expression of gshA and gshB1 was correspondingly reduced in the mutant under free-living and symbiotic conditions by analyses of real-time quantitative reverse transcription-polymerase chain reaction and promoter-GUS fusions. Interestingly, LsrB positively regulated the transcription of oxyR, which encodes another member of LysR family regulators and responds to oxidative stresses in S. meliloti. The oxyR null mutant produced less glutathione, in which the transcription of gshA was consistently down-regulated. These findings demonstrate that glutathione biosynthesis is positively regulated by both LsrB and OxyR in S. meliloti.


Phosphorus-31 nuclear magnetic resonance studies of the binding of nucleotides to NADP+-specific isocitrate dehydrogenase.
The interaction of the 2'-phosphate-containing nucleotides (NADP+, NADPH, 2'-phosphoadenosine 5'-diphosphoribose, and adenosine 2',5'-bisphosphate) with NADP+ -specific isocitrate dehydrogenase was studied by using 31P NMR spectroscopy. The separate resonances corresponding to free and bound nucleotides, characteristic for slow exchange of nuclei on the NMR time scale, were observed in the spectra of the enzyme (obtained in the presence of excess ligand) with NADP+ and NADPH in the absence and presence of Mg2+ and with 2'-phosphoadenosine 5'-diphosphoribose in the absence of metal or in the presence of the substrate magnesium isocitrate. The position of the 31P resonance of the bound 2'-phosphate group in these spectra is invariant (delta = 6) in the pH range 5-8, indicating that the pK of this group is much lower in the complexes with the enzyme than that (pK = 6.13) in the free nucleotides. The additional downfield shift of this resonance by 1.8 ppm beyond that (delta = 4.22) of the dianionic form of the 2'-phosphate in free nucleotides suggests interaction with a positively charged group(s) and/or distortion of P-O-P angles as the result of binding to the enzyme. A single resonance of 2'-phosphate was observed in the spectrum of the enzyme complex with 2'-phosphoadenosine 5'-diphosphoribose in the presence of Mg2+, with the chemical shift dependent on the nucleotide to enzyme ratio, characteristic for the fast exchange situation. Addition of metal does not perturb the environment of the 2'-phosphate in the complexes of NADP+ and NADPH with isocitrate dehydrogenase.(ABSTRACT TRUNCATED AT 250 WORDS)


High concentration of antimitochondrial antibodies predicts progressive primary biliary cirrhosis.
To evaluate the serum concentration of antimitochondrial antibodies (AMAs) as a prognostic indicator of progressive primary biliary cirrhosis (pPBC). Serum concentrations of AMA subtypes (anti-M2, anti-M4, and anti-M9), biochemical indices of liver function and Mayo risk factor (MRF) were determined in 30 women with diagnosed primary biliary cirrhosis (PBC) selected among 348 females with elevated alkaline phosphatase but without signs of hepatic decompensation. They were followed up for 5 years for possible development of hepatic decompensation. Anti-M2 concentration was significantly correlated with bilirubin and albumin levels as well as MRF, whereas anti-M4 was significantly correlated with albumin level, prothrombin time and MRF. During the 5-year follow-up, progressive PBC (pPBC) was diagnosed in 3 among 23 patients available for evaluation. These 3 patients were positive for both anti-M2 and anti-M4. Anti-M2 serum concentration exceeded 1 300 RU/mL in patients with pPBC and only in 1 among 20 non-progressive PBC persons (5%). Anti-M4 serum concentration exceeded 400 RU/mL in 2 of the progressive patients and none in the non-progressive group. In contrast, anti-M9 serum concentration was below 100 RU/mL in all patients with pPBC, and higher than 100 RU/mL in 11 women (55%) among the non-progressive group. Females with elevated alkaline phosphatase and high anti-M2 and anti-M4 concentrations are at a high risk for developing pPBC. Quantitative AMA detection should be considered as a method for early diagnosis of pPBC.


Successful treatment of intermittent claudication due to spinal canal stenosis using beraprost sodium, a stable prostaglandin I2 analogue. A case report.
The syndrome of intermittent claudication can be induced not only by vascular insufficiency of the lower limbs but also by diseases of the spinal cord and cauda equina. The authors describe a sixty-year-old man with intermittent claudication due to spinal canal stenosis who was successfully treated with beraprost sodium, a stable prostaglandin I2 analogue. This drug has a long biological half-life and is orally effective in vasodilation, which is suggested to be beneficial in treating this syndrome. Beraprost sodium may become one of the major drugs for conservative therapy of intermittent claudication induced by spinal canal stenosis.


Robust Anticancer Efficacy of a Biologically Synthesized Tumor Acidity-Responsive and Autophagy-Inducing Functional Beclin 1.
As a potent autophagy inducer, Beclin 1 is essential for the initiation of autophagic cell death, and triggering extensive autophagy by targeted delivery of Beclin 1 to tumors has enormous potential to inhibit tumor growth. Yet, the therapeutic application of Beclin 1 is hampered by its inability to internalize into cells and nonselective biodistribution in vivo. To tackle this challenge, we employed a novel Beclin 1 delivery manner by constructing a functional protein (Trx-pHLIP-Beclin 1, TpB) composed of a thioredoxin (Trx) tag, a pH low insertion peptide (pHLIP), and an evolutionarily conserved motif of Beclin 1. This protein could effectively transport Beclin 1 to breast and ovarian cancer cell lines under weakly acidic conditions (pH 6.5), markedly inhibit tumor cell growth and proliferation, and induce obvious autophagy. Furthermore, the in vivo antitumor efficacy of the functional Beclin 1 against an SKOV3 xenograft tumor mouse model was tested via intravenous injection. TpB preferentially accumulated in tumors and exhibited a significantly higher tumor growth inhibition than the nontargeted Beclin 1 control, whereas no overt side effects were observed. Taken together, this study sheds light on the potential application of TpB as a highly efficient yet safe antitumor agent for cancer treatment.


The P2X1 receptor, an adenosine triphosphate-gated cation channel, is expressed in human platelets but not in human blood leukocytes.
Extracellular adenosine triphosphate (ATP) and adenosine diphosphate (ADP) activate multiple types of P2-nucleotide receptors expressed in platelets or leukocytes. Electrophysiological and biochemical studies have indicated expression of the P2X1 receptor, an ATP-gated cation channel, in human and rat platelets, rat basophilic leukemia (RBL) cells, and phorbol myristate acetate (PMA)-differentiated HL-60 myeloid cells. Although these findings suggest that P2X1 receptors are present in both blood leukocytes and blood platelets, the relative levels of P2X1 receptor expression and function in human blood leukocytes and platelets have not been directly characterized. On the basis of both immunoblot analysis and functional assays of P2X1 receptor-mediated ionic fluxes, we report that there is significant expression of P2X1 receptors in human platelets, but not in neutrophils, monocytes, or blood lymphocytes. Thus, unlike platelets and myeloid progenitor cell lines, fully differentiated human blood leukocytes do not express functionally significant numbers of P2X1 receptors, suggesting the downregulation of P2X1 receptor gene expression during the differentiation of phagocytic leukocytes. By contrast, P2X1 receptor expression is strongly maintained during megakaryocytic differentiation and platelet release. Immunoblot analysis indicated that the platelet P2X1 receptor migrates as an approximately 60-kD protein during SDS-electrophoresis under reducing or nonreducing conditions. Treatment of platelet membranes with endoglycosidase-F causes the P2X1 receptor band to migrate as a 46-kD protein, verifying the highly glycosylated nature of the mature receptor protein. Additional studies of nucleotide-induced changes in Ca2+ influx/mobilization demonstrated that the platelet P2X1 receptors are pharmacologically distinct from the well-characterized ADP receptors of these cells. This finding suggests a unique role for these ATP-gated ion channels during hemostasis or thrombosis.


Primary neuroendocrine tumors of the thymus: Clinical review of 22 cases.
Primary neuroendocrine tumors of the thymus are rare mediastinum tumors, which present a distinct type of tumor, which exhibit morpholgical and biological neuroendorcine features including the production of numerous biogenic amines. The aim of the present study was to evaluate factors influencing long-term survival in patients with primary neuroendocrine tumors of the thymus. A total of 22 patients exhibiting primary thymic neuroendocrine tumors, who were treated at the Zhejiang Cancer Hospital (Hangzhou, China), between 1995 and 2012 were reviewed. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model was used for multivariate analysis. The overall five-year survival rate was 45.5% and the median survival time was 59 months in all of the patients. Histological grade (P<0.001), Masaoka-Koga stage (P=0.003) and surgical resection status (P=0.004) were identified to be associated with patient survival time. Furthermore, multivariate analysis identified that the histological grade was an independent prognostic factor, which was applicable to all patients (P=0.009). Therefore, the histological grade and Masaoka-Koga stage, as well as surgical resection status present three prognostic factors in patients exhibiting primary thymic neuroendocrine tumors.


Representation of con-specific vocalizations in the core and belt areas of the auditory cortex in the alert macaque monkey.
Auditory cortical processing in primates has been proposed to be divided into two parallel processing streams, a caudal spatial stream and a rostral nonspatial stream. Previous single neuron studies have indicated that neurons in the rostral lateral belt respond selectively to vocalization stimuli, whereas imaging studies have indicated that selective vocalization processing first occurs in higher order cortical areas. To test the dual stream hypothesis and to find evidence to account for the difference between the electrophysiological and imaging results, we recorded the responses of single neurons in core and belt auditory cortical fields to both forward and reversed vocalizations. We found that there was little difference in the overall firing rate of neurons across different cortical areas or between forward and reversed vocalizations. However, more information was carried in the overall firing rate for forward vocalizations compared with reversed vocalizations in all areas except the rostral field of the core (area R). These results are consistent with the imaging results and are inconsistent with early rostral cortical areas being involved in selectively processing vocalization stimuli based on a firing rate code. They further suggest that a more complex processing scheme is in play in these early auditory cortical areas.


DNA diagnosis for the detection of sickle hemoglobinopathies.
At this time, the sole generally accepted use for DNA diagnosis in the hemoglobinopathies is for the prenatal detection of disease, which can be identified by these means early in the first trimester of pregnancy. By ascertaining genotype rather than phenotype, the confusion that results from diagnostic errors should be diminished. DNA diagnostics are the future of all genetic disease detection and this future will soon be upon us.


Endovascular aneurysm repair or open surgery for treatment of abdominal aortic aneurysm with involvement of both common iliac arteries?
Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) involving the entire common iliac arteries requires proximal coil embolisation of both internal iliac arteries and extension of the stent graft into the external iliac arteries (type E according to the Eurostar classification). A potential complication of this treatment is pelvic ischemia. Therefore, this type of aneurysm is a relative contra-indication for EVAR. In this case-report we describe a hybrid procedure preserving antegrade circulation in one of the internal iliac arteries in a patient with a type E aneurysm who was unfit for open surgery.


Reoperation for recurrent trigeminal neuralgia after microvascular decompression.
Microvascular decompression (MVD) is an effective technique for those who have trigeminal neuralgia (TN) but cannot tolerate, or show no response to medicine. Though the initial success rate is high, some patients may develop severe recurrent neuralgia, especially after a longer period of follow-up. The efficacy of reoperation needs to be evaluated. To know the possible risk factors of recurrence after initial MVD is mandatory to the management of recurrent TN. Among the 80 cases of TN treated with MVD, five cases showed severe recurrent symptoms within a follow-up period from 9 months-4 years. The symptoms recurred on the same side of the face, and were unresponsive to medical treatment. Brain computed tomography (CT) and magnetic resonance imaging (MRI) may reveal the etiology of recurrence. Repeat decompression of the trigeminal nerve was the main goal of reoperation, which was done via a suboccipital approach. Over the past 17 years, 80 MVDs for TN have been performed at Chang Gung Memorial Hospital. There were five cases of serious postoperative recurrence, which could not be relieved by medicine. Recurrence occurred 1 day-12 months after the initial surgery. Three cases were due to vascular compression, while two were caused by the local effect of Teflon felt. Reoperation produced complete remission in four patients, and partial remission in one. An increasing number of patients may experience severe recurrent TN after initial MVD during a long period of follow-up. Reoperation is safe and beneficial for these patients, but the results are dependent on the etiology of the recurrence. Further vascular compression of the trigeminal nerve can be relieved by MVD. Otherwise, in cases of severe adhesion caused by Teflon, complete microneural lysis can achieve satisfactory results.


A commercial enzyme immunoassay method (EMIT) compared with liquid chromatography and bioassay methods for measurement of chloramphenicol.
A new enzyme immunoassay method (EMIT; Syva Co.) was compared with conventional high-performance liquid chromatography (HPLC) and agar-diffusion bioassay methods for measurement of chloramphenicol in human serum. Forty-nine serum samples were assayed by each of the three methods. Excellent correlation was observed between values by EMIT and by the two conventional methods (r = 0.986 and 0.961). Precision was acceptable (CV less than 5%) with EMIT. Assay of samples containing chloramphenicol glucuronide and chloramphenicol succinate demonstrated that EMIT recognizes only the biologically active (base) form of the drug. The capability to test serum samples as small as 0.2 mL, adaptation to widely available instrumentation, and provision of rapid results are principal advantages of the EMIT method for routine chloramphenicol measurements.


More Reasonable Animal Model for Study the Effect of Pneumoperitoneum on Abdominal Tumor Cells
Background: Many animal experimental studies showed that abdominal tumor cells will be widely spread during laparoscopic treatment and grow into metastases. These results are different from clinical observations. There is a hypothesis that too much tumor cells was injected in the animals lead to the results of theses bias. We aim to learn the difference of abdominal cavity volume between human body and the nude mice and to determine reasonable amount of tumor cells in the animal experiments. Methods: The insufflated CO2 volume which represents the capacity of the abdominal cavity was recorded during laparoscopic process in 212 patients and 20 nude mice respectively, the relative volume of nude mice and human body was calculated.Based on data from the literature and this study , the amount of tumor cells in the animal experiments was determined.According to these data, we set up a new animal model and a traditional one respectively,and compared the rate of successful modeling and tumor formation between two animal models. Results: The intraperitoneal volumes of humans and nude mice were 3.01±0.36 L and 0.011±0.001 L respectively.The number of tumor cells that be uesd in animal should be approximately 0.26×105 in terms of known data in human beings.Compared with the traditional animal model which formed a large number of intraperitoneal tumor metastasis, the new animal model was shows more moderately,and the rate of successful modeling was similar. Conclusion: In animal experiments, to simulate the clinical situation, about 0.26×105 tumor cells should be inject in peritoneal cavity of the nude mice.


Case Series: Herpes Zoster Ophthalmicus with Acute Orbital Inflammation.
Herpes zoster ophthalmicus (HZO) has variable initial manifestations, and acute orbital inflammation may be the first sign without apparent zoster rash. This case series is significant for presenting diverse clinical features and treatment options of HZO with acute orbital inflammation. To report a case series of patients diagnosed as HZO with acute orbital inflammation including two cases with unique presentations. Medical records of four patients of HZO with acute orbital inflammation were reviewed. Two men and two women with a median age of 57 years (range, 32 to 69 years) were diagnosed as having HZO with acute orbital inflammation. Initial presentations included two cases of zoster rash and two cases of orbital pain preceding vesicles. Clinical orbital findings included proptosis, ptosis, ophthalmoplegia, and decreased visual acuity. Orbital magnetic resonance image showed enlarged extraocular muscle with enhancement and optic nerve sheath enhancement in all four patients, and unilateral dacryoadenitis in one patient. All four patients were administered with systemic steroid, three patients received intravenous acyclovir, and one patient received oral acyclovir. Orbital signs improved in all patients over several months. Herpes zoster ophthalmicus may initially present with orbital inflammatory signs, such as acute orbital myositis, perioptic neuritis, or dacryoadenitis, without zoster rash. Physicians should be aware of acute orbital inflammation as a presenting sign of HZO.


Association of activated Gαq to the tumor suppressor Fhit is enhanced by phospholipase Cβ.
G proteins are known to modulate various growth signals and are implicated in the regulation of tumorigenesis. The tumor suppressor Fhit is a newly identified interaction partner of Gq proteins that typically stimulate the phospholipase C pathway. Activated Gαq subunits have been shown to interact directly with Fhit, up-regulate Fhit expression and enhance its suppressive effect on cell growth and migration. Other signaling molecules may be involved in modulating Gαq/Fhit interaction. To test the relationship of PLCβ with the interaction between Gαq and Fhit, co-immunoprecipication assay was performed on HEK293 cells co-transfected with different combinations of Flag-Fhit, Gα16, Gα16QL, pcDNA3 vector, and PLCβ isoforms. Possible associations of Fhit with other effectors of Gαq were also demonstrated by co-immunoprecipitation. The regions of Gαq for Fhit interaction and PLCβ stimulation were further evaluated by inositol phosphates accumulation assay using a series of Gα16/z chimeras with discrete regions of Gα16 replaced by those of Gαz. PLCβ1, 2 and 3 interacted with Fhit regardless of the expression of Gαq. Expression of PLCβ increased the affinities of Fhit for both wild-type and activated Gαq. Swapping of the Fhit-interacting α2-β4 region of Gαq with Gαi eliminated the association of Gαq with Fhit without affecting the ability of the mutant to stimulate PLCβ. Other effectors of Gαq including RGS2 and p63RhoGEF were unable to interact with Fhit. PLCβ may participate in the regulation of Fhit by Gq in a unique way. PLCβ interacts with Fhit and increases the interaction between Gαq and Fhit. The Gαq/PLCβ/Fhit complex formation points to a novel signaling pathway that may negatively regulate tumor cell growth.


Treatment of a celiac artery aneurysm with endovascular stent grafting--a case report.
As a result of more sophisticated and more commonly performed investigative procedures, aneurysms of the visceral abdominal vasculature, including celiac artery aneurysms, are increasingly recognized. Traditional therapy for visceral artery aneurysms has been limited to open aneurysmectomy or aneurysmorrhaphy to prevent catastrophic aneurysmal rupture. However, these procedures are associated with significant postoperative morbidity and mortality despite technical successes. High complication rates are likely related to poor preoperative conditions among the patient population typically presenting with these visceral artery aneurysms. This report introduces an alternative therapy for visceral artery aneurysms and highlights the potential for catheter-based interventions. This case report depicts a 61-year-old morbidly obese woman diagnosed with a 10-centimeter celiac artery aneurysm during investigation of upper abdominal pain. Given the patient's poor medical condition, punctuated by hemodynamic instability, open operation was avoided, and percutaneous embolization was not feasible owing to a large aneurysm neck. Therefore, inflow to the celiac artery aneurysm was excluded by placing a modular stent graft component within the abdominal aorta at the celiac artery orifice. During the intervening 12 months since stent graft deployment, the aneurysm sac diameter has steadily decreased, as determined by serial computed tomography scans. This report underscores the potential for catheter-based techniques to offer new therapeutic options for patients with visceral artery aneurysms. Careful individualization is required given the highly variable size, location, and character of such lesions.


Effect of class I and II organic modifiers on retention and selectivity in vesicle electrokinetic chromatography.
Vesicles are large aggregates of surfactant monomers consisting of a spherical bilayer surrounding an internal cavity of solvent. The bilayer structure allows vesicles to be attractive models for the study of various transmembrane and binding processes. The use of thermodynamically stable vesicles (TSV) formed from oppositely charged surfactants for use as a pseudostationary phase in electrokinetic chromatography (EKC) was first accomplished using dodecyltrimethylammonium bromide and sodium dodecyl sulfate (DTAB/SDS). Surfactant vesicles have demonstrated enhanced separation characteristics compared to conventional micelles in EKC, although only investigated in aqueous media. Organic modifiers have been widely studied and used in EKC to enhance separation conditions. In this study, vesicles formed from cetyltrimethylammonium bromide and sodium octyl sulfate (CTAB/SOS) were investigated in the presence of "class I and II" organic modifiers. Electrophoretic and chromatographic parameters were examined as well as linear solvation energy relationship analysis (LSER) to characterize the effects of the modifiers on retention and selectivity in EKC. LSER analysis is a useful way to quantitatively investigate solute/solvent interactions responsible for retention and selectivity.


Collective nature of the boson peak and universal transboson dynamics of glasses.
Using probe molecules with resonant nuclei and nuclear inelastic scattering, we are able to measure the density of states exclusively for collective motions with a correlation length of more than approximately 20 A. Such spectra exhibit an excess of low-energy modes (boson peak). This peak behaves in the same way as that observed by conventional methods. This shows that a significant part of the modes constituting the boson peak is of collective character. At energies above the boson peak, the reduced density of states of the collective motions universally exhibits an exponential decrease.


Confocal Laser Endomicroscopic Findings of Refractory Erosive Reflux Disease versus Non-Erosive Reflux Disease with Anti-Reflux Mucosectomy: An in vivo and ex vivo Study.
To date, there is no standard tool to diagnose gastroesophageal reflux disease (GERD). Typically, GERD is a non-erosive reflux disease (NERD) that does not present endoscopic abnormalities. Confocal laser endomicroscopy (CLE) has been shown to be an effective tool to identify and diagnose GERD. We aimed to investigate the cellular and vascular changes in vivo and ex vivo through CLE in patients with GERD. Patients with refractory GERD who underwent mucosectomy were recruited. The distal esophagus was observed in vivo using CLE. Mucosectomy tissue was stained with acriflavine and CLE image was obtained ex vivo. We compared cellular and vascular changes in CLE between erosive reflux disease (ERD), NERD, and a control group. Eleven patients who underwent anti-reflux mucosectomy and five control patients were enrolled in the study. Patients with ERD and NERD presented greater dilated intercellular space than patients in the control group on CLE image. The diameter, number, and cross-sectional area of the intra-papillary capillary loops (IPCLs) were significantly larger in the ERD group than in the NERD group. The irregular shape of the IPCLs were observed in both patients with ERD and NERD. The irregular shape of the IPCLs were significantly correlated with a positive diagnosis of GERD. CLE may diagnose NERD with high sensitivity and accuracy.


Microbial Food Safety in China: Past, Present, and Future.
Food safety is a major public health issue worldwide, especially in heavily populated countries such as China. As in other countries, the predominant food safety issues in China are foodborne diseases caused by microbial pathogens. Hence, this review provides a systematic overview on microbial food safety in the past, present, and future in China. Management of microbial food safety in China is generally divided into three stages: Stage I before 2000, Stage II from 2000 to 2009, and Stage III from 2010 to present. At Stage I, China's main food concern gradually shifted from food security to food safety. At Stage II, foodborne pathogen surveillance was initiated and gradually became a focus of microbial food safety marked by the establishment of national food contamination monitoring system in 2000 and the promulgation of China Food Safety Law in 2009, although chemical food safety was considered a priority issue during this stage. At Stage III, microbial food safety was recognized as a high priority supported by many national food safety policies such as the launch of a national foodborne disease molecular tracing network in 2013 and the revision of China Food Safety Law in 2015. Advancement in food safety education and research support by central and local governments has also made significant contributions to tackling and solving microbial food safety problems. Management in the future should be focused on active involvement of food industries in mitigating microbial risks by introducing ISO 22000, regulatory enforcement to oversee compliances to standards and rules, and application of molecular tools for fast detection and source tracking to support decision-making. Future research efforts may include, but are not limited to, exploitation of interaction mechanisms among pathogenic bacteria, food and gut microbiota, smart traceability of microbial hazards, and development of novel antimicrobial strategies.


Primary intestinal follicular lymphoma: How to identify follicular lymphoma by routine endoscopy.
A 69-year-old Japanese female was diagnosed with primary intestinal follicular lymphoma. Esophagogastroduodenoscopy with high-definition imaging revealed not only the typical feature of whitish polyps of up to 2 mm in diameter in the duodenal second and third portions, but also more detailed morphology, such as enlarged whitish villi and tiny whitish depositions. These findings appeared to reflect the pathological structures; infiltration of lymphoma cells into the villi were probably seen as enlargement of the villi, and the formation of lymphoid follicles were shown as opaque white spots or tiny white depositions. Thus, the above features might contribute to the distinct diagnosis of intestinal follicular lymphoma. This case indicates that routine esophagogastroduodenoscopy can visualize microsurface structures, which can be pathognomonic and help to diagnose intestinal follicular lymphoma, even without magnifying endoscopy.


[Evaluation of local treatment for unresectable primary liver tumor].
To ascertain the effect of local treatment for unresectable primary liver tumor, 59 patients were investigated retrospectively. Patients were classified into four groups; transcatheter arterial embolization (TAE) group, intermittent intra-arterial infusion chemotherapy group, combined therapy group (TAE+intermittent intra-arterial infusion chemotherapy) and a group without adjuvant therapy. The results revealed that TAE and intermittent intra-arterial infusion chemotherapy both prolonged the survival period. We found that the survival rate depends largely on the therapeutic method. No correlations were confirmed with the liver function nor stage grouping of the tumor. Therefore, we concluded that intermittent intra-arterial infusion chemotherapy is a beneficial treatment, considering its minimal adverse effect, broad indication and the fact that it does not require hospitalization.


Study of Biomass Composite Workpiece Support Structure Based on Selective Laser Sintering Technology.
When using selective laser sintering to print parts with thin-walled structures, the thermal action of the laser can cause thermal stresses that lead to plastic deformation, resulting in large warpage and dimensional deviations. To address this issue, this study proposes a bottom support method for selective laser sintering. The impact of lattice-type, concentric-type, and cross-type support structures with varying filling densities and thicknesses on the suppression of warpage and dimensional errors was investigated. The optimal process parameters for each support structure were then determined through optimization. The findings of this study demonstrated a reduction in Z-axis dimensional errors of the workpiece following the addition of supports. The reduction amounted to 33.809%, 86.160%, and 66.214%, respectively, compared to the original workpiece. Moreover, the corresponding warpage was reduced by 35.673%, 46.189%, and 46.059% for each respective case, showcasing an improvement in the printing precision. Therefore, the bottom support effectively reduces dimensional and shape errors in thin-walled parts printed by selective laser sintering. Specifically, the results obtained indicated that the concentric type of support is more effective in reducing dimensional errors and enhancing the shape accuracy of the printed workpiece. Conversely, the cross type of support demonstrated superior capabilities in minimizing the consumption of printing materials while still delivering satisfactory results. Thus, this study holds promise for contributing to the advancement of thin-walled part quality using selective laser sintering technology. This research can contribute to achieving greater accuracy in the fabrication of parts through 3D printing.


[Is antihypertensive treatment a risk factor of coronary disease? Therapy-related triglyceride increase nor diabetes increase the risk].
In an observational study designed to determine whether metabolic changes during long-term antihypertensive drug treatment are associated with an increased risk of coronary heart disease (CHD), 686 middle-aged hypertensive men recruited from a random population screening sample were followed up for 15 years. Antihypertensive treatment predominantly consisted of beta-adrenoceptor blockers and/or thiazide diuretics. CHD and diabetes mellitus were checked for at annual examinations. Time-dependent Cox regression analysis was used to determine correlation between the incidence of CHD and entry characteristics, the monitored serum levels of cholesterol and triglyceride concentrations and the development of diabetes mellitus. Univariate analysis showed the presence of diabetes mellitus a entry to the study and increased baseline serum concentrations of cholesterol and of triglycerides each to be a significant predictor of CHD, the respective relative risks (RR) being 2.12, 1.21 and 1.21. However, analysis of monitored levels of metabolic variables during follow-up showed only an increased serum cholesterol concentration to be significantly and independently associated with CHD (RR 1.07). Although serum triglyceride concentrations increased slightly during follow-up, they were unrelated to the incidence of CHD; nor was onset of diabetes mellitus during follow-up significantly associated with an increased risk of CHD (RR 1.48. Thus, the study showed the presence of metabolic disturbances such as diabetes mellitus and hyperlipidaemia before the start of antihypertensive treatment to be of positive predictive value in middle-aged hypertensive men, and an increase in the monitored serum cholesterol level to be an independent predictor of CHD, whereas neither drug-related diabetes nor an increase in the monitored serum triglyceride concentration seemed to be associated with the occurrence of CHD.


Adult Zebrafish (Danio rerio): An Alternative Behavioral Model of Formalin-Induced Nociception.
The zebrafish (Danio rerio) has been proposed as a low-cost and simple alternative to the use of higher vertebrates in laboratory research on novel compounds with antinociceptive potential. In this study, we tested adult zebrafish (Danio rerio) as an alternative behavioral model of formalin-induced nociception. We evaluated the nociceptive effect of 0.1% formalin (3 or 5 μL; intramuscularly [i.m.]), applied into the tail or lips, on locomotor activity, using as parameter the number of times the fish crossed the lines between the quadrants of a glass Petri dish during the neurogenic stage (0-5 min) and the inflammatory stage (15-30 min). The behavioral model was validated by testing the antinociceptive effect of morphine and indomethacin (standard analgesic drugs used in the formalin test of rodents). We also tested whether the effect of morphine could be modulated by naloxone, an opioid antagonist. The effect of morphine and indomethacin on zebrafish locomotor behavior was evaluated with the open field test. The white/black test was used to rule out the anxiolytic effect of 0.1% formalin injected into the tail on adult zebrafish. Formalin (0.1%; 3 and 5 μL injected into the tail) increased significantly the nociceptive behavior of the adult zebrafish in both stages (p < 0.001 vs. control). Morphine and indomethacin (both 0.2 mg/mL; 20 μL; intraperitoneally [i.p.]) significantly inhibited nociception induced with formalin (5 μL injected i.m. into the tail) in both stages (p < 0.001). Naloxone blocked the antinociceptive effect of morphine. No influence on locomotion was observed. Locally administered formalin (injected into the tail) induced nociception, but not anxiety. The results suggest that the adult zebrafish behavioral model is a feasible alternative to more conventional laboratory models used in research on novel compounds with antinociceptive potential.


The Intervention of CRAC Channels Alleviates Inflammatory Responses in Nasal Polyps.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with Th2-dominant inflammation. However, effective treatments for CRSwNP have not yet been found. This study aimed to investigate the expression of Orai1 in nasal polyps (NP) and the influence on them of the intervention of Ca2+ release-activated Ca2+ (CRAC) channels. Nasal samples were obtained from normal subjects or subjects with CRSwNP. We studied the distribution of Orai1 protein in NP and normal mucosa (normal group) using immunohistochemistry. These tissues in cultures were then maintained in the absence (control group) or presence of 2-aminoethoxydiphenyl borate (2-APB) for 24 h. Orai1 was examined by means of enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (RT-PCR). The Ca2+ mean fluorescence intensity (MFI) was evaluated by flow cytometry, and the inflammatory mediators, including interleukin (IL)-4, IL-5, IL-13, Dermatophagoides pteronyssinus-specific IgE, leukotriene C4 and eosinophil cation protein in cultures, were analyzed with ELISA and real-time RT-PCR. The expression of Orai1 was localized to the cytoplasmic membrane of inflammatory cells, and upregulated in NP compared to that in the normal group. However, Orai1 protein was decreased in polyp tissues after the 2-APB treatment. The levels of Ca2+ MFI and above inflammatory mediators were also elevated in NP, and reduced after the 2-APB administration compared to those in the control group. Orai1 and CRAC channels may play a crucial role in NP formation and development, and the 2-APB intervention of Orai1 protein may alleviate inflammatory responses in NP.


Depth perception of elementary school students with qualitatively evidenced locomotor impairments.
The purpose of the study was to examine differences in depth perception of students classified according to their gross locomotor skills. The seven qualitative gross locomotor tasks of Ulrich's Test of Gross and Motor Development were used to classify 162 students as either motor impaired (n1 =27) or nonimpaired (n2= 135). The Howard Dollman Apparatus was used to measure depth perception. Analysis showed that the motor-impaired group scored significantly lower than the nonimpaired group on depth perception. Discriminant function analysis indicated that only the running task separated the students by depth perception scores. Subsequent multiple regression analysis confirmed that the running task, along with sliding and galloping, were significant predictors of the students' perception of the third dimension. Physical educators working with students with gross locomotor impairments or low perception of the third dimension need to adjust their teaching and offer opportunities for successful involvement in physical education classes and sports.


Some pharmacological properties of a newly synthesized morphine derivative, (-)-6 beta-acetylthiomorphine.
Some pharmacological properties of a newly synthesized morphine derivative, (-)-6 beta-acetylthiomorphine (AcS-morphine) were studied. AcS-morphine was about twice as potent as morphine in the inhibitory action of the twitch response of the guinea-pig ileal preparation to electrical stimulation. AcS-morphine, however, was 5 times as potent as morphine in the analgesic action in the rats. Both the effects of AcS-morphine were inhibited by naloxone, suggesting that the site of action of AcS-morphine is mu-receptors. It is interesting that 6 beta-isomer of AcS-morphine is 5 times as potent as 6 alpha-OH isomer of morphine in the analgesic action, because 6 alpha-OH isomer of morphine is much more potent than that of 6 beta-OH isomer. The effects of AcS-morphine on the specific binding of [3H]-naloxone, [3H]-ethylketocyclazocine and [3H]-D-Ala2-D-Leu5-enkephalin to the membrane fractions from the rat brain were tested. AcS-morphine was about 5 times as potent as morphine in its interactions with opioid receptors, as determined by the binding assay. AcS-morphine, as well as morphine, had a selectively high affinity to mu-receptors. The "sodium effect" and the "GTP effect" of AcS-morphine were almost the same as those of morphine. The dependence liability of AcS-morphine was preliminary tested in the guinea-pig ileal preparations treated with a high concentration of AcS-morphine for 24 hr. Results suggested that AcS-morphine is weaker than morphine in its dependence liability, though it seems almost certain that AcS-morphine does have this liability.


Closed-loop rehabilitation of age-related cognitive disorders.
Cognitive deficits are common in older adults, as a result of both the natural aging process and neurodegenerative disease. Although medical advancements have successfully prolonged the human lifespan, the challenge of remediating cognitive aging remains. The authors discuss the current state of cognitive therapeutic interventions and then present the need for development and validation of more powerful neurocognitive therapeutics. They propose that the next generation of interventions be implemented as closed-loop systems that target specific neural processing deficits, incorporate quantitative feedback to the individual and clinician, and are personalized to the individual's neurocognitive capacities using real-time performance-adaptive algorithms. This approach should be multimodal and seamlessly integrate other treatment approaches, including neurofeedback and transcranial electrical stimulation. This novel approach will involve the generation of software that engages the individual in an immersive and enjoyable game-based interface, integrated with advanced biosensing hardware, to maximally harness plasticity and assure adherence. Introducing such next-generation closed-loop neurocognitive therapeutics into the mainstream of our mental health care system will require the combined efforts of clinicians, neuroscientists, bioengineers, software game developers, and industry and policy makers working together to meet the challenges and opportunities of translational neuroscience in the 21st century.


Towards a balanced approach to identifying conflicts of interest faced by institutional review boards.
The welfare and protection of human subjects is critical to the integrity of clinical investigation and research. Institutional review boards (IRBs) were thus set up to be impartial reviewers of research protocols in clinical research. Their main role is to stand between the investigator and her human subjects in order to ensure that the welfare of human subjects are protected. While there is much literature on the conflicts of interest (CIs) faced by investigators and researchers in clinical investigations, an area that is less explored is CIs that may affect members of IRBs during the institutional ethics review of clinical investigations. This article examines the notion of CIs in clinical research and attempts to develop a framework for a clearer and more balanced approach to identifying CIs that may influence members of IRBs and impede their independence. It will also apply the proposed framework to demonstrate how IRBs possess, or at least may appear to possess, forms of financial CIs and non-financial CIs. The proper identification and management of these CIs is critical to preserving the integrity of clinical investigations and achieving the primary aim of human subjects protection.


Initial transfusion intensity predicts survival in myelodysplastic syndrome.
We evaluated 52 patients with myelodysplastic syndrome (MDS) who had received at least one red blood cell (RBC) transfusion. In the 4-week period following the first transfusion, 24 patients (group 1) required no transfusion, while 28 (group 2) required transfusion of two or more units of RBCs. Survival was greater in group 1 (440 weeks vs. 167 weeks, p < 0.01), even when only international prognostic scoring system (IPSS) low and intermediate-1 risk patients were analyzed (median overall survival 491 vs. 170 weeks, p < 0.05), independent of age, IPSS and progression to acute myeloid leukemia (AML). The intensity of transfusion required in the first few weeks after the first transfusion predicts disease severity and correlates with survival.


Transversal optical singularity induced precision measurement of step-nanostructures.
Optical singularities indicate zero-intensity points in space where parameters, such as phase, polarization, are undetermined. Vortex beams such as the Laguerre-Gaussian modes are characterized by a phase factor eilθ, and contain a phase singularity in the middle of its beam. In the case of a transversal optical singularity (TOS), it occurs perpendicular to the propagation, and its phase integral is 2π in nature. Since it emerges within a nano-size range, one expects that TOSs could be sensitive in the light-matter interaction process and could provide a great possibility for accurate determination of certain parameters of nanostructure. Here, we propose to use TOSs generated by a three-wave interference to illuminate a step nanostructure. After interaction with the nanostructure, the TOS is scattered into the far field. The scattering direction can have a relation with the physical parameters of the nanostructure. We show that by monitoring the spatial coordinates of the scattered TOS, its propagation direction can be determined, and as consequence, certain physical parameters of the step nanostructure can be retrieved with high precision.


Respiratory function and cosmesis at maturity in infantile-onset scoliosis.
Retrospective review of patient records, clinical and radiographic, and patient recall for full pulmonary function studies and surface topography. Assessment of outcome of treatment policy after age 15 during the previous 30 years to establish the efficacy of management protocols in a group that is too small and too varied for more formal assessment. Spinal deformity presenting during infancy or early childhood poses a clinical problem caused by small numbers, long growth period, variable presentation and treatment methods, and, finally, the length of time that must pass before meaningful outcome results can be assessed. The aims of treatment are to preserve respiratory function and cosmetic appearance. The records of patients with infantile onset, nonsyndromic, and noncongenital scoliosis were reviewed. Thirty two were at least age 15 years at the time of review and 21 of these agreed to attend for full pulmonary function testing (spirometry, lung volumes, gas diffusion) and surface topography, whereas two more had recent spirometry results available in their record. Treatment had been serial casting with Risser jacket, bracing, or surgery. Those whose scoliosis resolved or was stabilized by nonoperative means (N = 6) at an acceptable Cobb angle had normal cosmesis and pulmonary function (mean FEV1 = 98.7%, mean FVC = 96.6%). Those who were managed by casting or bracing and underwent surgery after age 10 (N = 6, mean age at surgery 12.9 y) had variable cosmesis and acceptable pulmonary function (mean FEV1 = 79%, mean FVC = 68.3%). Those whose deformity necessitated early surgery (N = 11, mean age at surgery 4.1 y) had recurrence of deformity and diminished respiratory function (mean FEV1= 41%, range 14%-72%, mean FVC = 40.8%, range 12%-67%). Although these are small numbers and treatment methods have changed since the beginning of the series, the results indicate that this condition is not simple to treat and for some children still has the risk for serious deformity and respiratory compromise. There is, as yet, no evidence that early surgical intervention in this group of patients with infantile scoliosis has altered their prognosis in any meaningful way.