Effects of agar and pectin on gastric emptying and post-prandial glycaemic profiles in healthy human volunteers.
1. Dietary fibre, such as pectin, delays gastric emptying and may enhance post-prandial glucose tolerance. Agar, which is high in fibre content, is widely used in the traditional Japanese diet. Although long-term diet therapy with agar decreases fasting plasma glucose levels in diabetes, knowledge is lacking about the acute effects of agar on gastric emptying and the post-prandial glycaemic profiles. The present study was designed to investigate the acute effects of agar. 2. Ten healthy male volunteers were studied on three occasions with three different test meals (450 kcal/500 mL): (i) a fibre-free meal; (ii) a meal with 2.0 g agar; or (iii) a meal with 5.2 g pectin. On each occasion, participants underwent a [(13)C]-acetate breath test along with serial blood sampling. To quantify gastric emptying, the half [(13)CO(2)] excretion time (t((1/2)b)) and the time for maximal [(13)CO(2)] excretion rate (t(lag)) were determined. The post-prandial glycaemic response was expressed as an incremental change from the fasting value at each sampling time. Data were analysed using repeated-measures analysis of variance (anova), followed by a post hoc paired Student's t-test with Bonferroni adjustment. 3. The time-course for respiratory [(13)CO(2)] excretion differed significantly among the three test meals (P = 0.0004, anova). Compared with the control meal, [(13)CO(2)] excretion was significantly lower following consumption of the agar meal (between 40 and 105 min post-prandially; P < 0.025, Student's t-test) and the pectin meal (between 40 and 180 min post-prandially; P < 0.025, Student's t-test). Among the three meals, significant differences were found in t((1/2)b) (P = 0.002, anova) and t(lag) (P = 0.011, anova). Compared with the control meal, the agar and pectin meals exhibited a significantly prolonged t((1/2)b) (P = 0.007 and P < 0.0001, respectively, Student's t-test) and t(lag) (P = 0.006 and P = 0.002, respectively, Student's t-test). Neither the agar nor pectin meal affected the post-prandial glucose profile. 4. In healthy adults, agar and pectin delay gastric emptying but have no impact on the post-prandial glucose response.


Electrically tunable nonlinear plasmonics in graphene nanoislands.
Nonlinear optical processes rely on the intrinsically weak interactions between photons enabled by their coupling with matter. Unfortunately, many applications in nonlinear optics are severely hindered by the small response of conventional materials. Metallic nanostructures partially alleviate this situation, as the large light enhancement associated with their localized plasmons amplifies their nonlinear response to record high levels. Graphene hosts long-lived, electrically tunable plasmons that also interact strongly with light. Here we show that the nonlinear polarizabilities of graphene nanoislands can be electrically tuned to surpass by several orders of magnitude those of metal nanoparticles of similar size. This extraordinary behaviour extends over the visible and near-infrared spectrum for islands consisting of hundreds of carbon atoms doped with moderate carrier densities. Our quantum-mechanical simulations of the plasmon-enhanced optical response of nanographene reveal this material as an ideal platform for the development of electrically tunable nonlinear optical nanodevices.


Forearm Motion Recognition With Noncontact Capacitive Sensing.
This study presents a noncontact capacitive sensing method for forearm motion recognition. A method is proposed to record upper limb motion information from muscle contractions without contact with human skin, compensating for the limitations of existing sEMG-based methods. The sensing front-ends are designed based on human forearm shapes, and the forearm limb shape changes caused by muscle contractions will be represented by capacitance signals. After implementation of the capacitive sensing system, experiments on healthy subjects are conducted to evaluate the effectiveness. Nine motion patterns combined with 16 motion transitions are investigated on seven participants. We also designed an automatic data labeling method based on inertial signals from the measured hand, which greatly accelerated the training procedure. With the capacitive sensing system and the designed recognition algorithm, the method produced an average recognition of over 92%. Correct decisions could be made with approximately a 347-ms delay from the relaxed state to the time point of motion initiation. The confounding factors that affect the performances are also analyzed, including the sliding window length, the motion types and the external disturbances. We found the average accuracy increased to 98.7% when five motion patterns were recognized. The results of the study proved the feasibility and revealed the problems of the noncontact capacitive sensing approach on upper-limb motion sensing and recognition. Future efforts in this direction could be worthwhile for achieving more promising outcomes.


Specific M2-receptor activation: an alternative to treatment with beta-receptor blockers?
A major complication of acute myocardial ischaemia is the occurrence of malignant tachyarrhythmias, which may partly be due to a transient increase in cellular sensitivity to adenylyl cyclase (AC) stimulation by catecholamines. Consequently, prevention of AC stimulation by beta-receptor blocking agents is effective in reducing the incidence of these arrhythmias. Activation of AC, however, can also be prevented by endogenous mechanisms through activation of inhibitory G-proteins (Gi), mediated by muscarinic M2-, adenosine A1-, and perhaps alpha 2-adrenergic receptors. Activation of Gi during myocardial ischaemia could have some advantages, since Gi not only mediates inhibition of AC but also promotes cellular hyperpolarization in atria and in the conduction system. In accordance with these considerations, there is growing evidence that activation of the cholinergic system may prevent ischaemia-induced tachyarrhythmias. However, the potential beneficial effect of cholinergic stimuli may be attenuated, as the muscarinic receptor-mediated inhibition of presynaptic exocytotic norepinephrine release is reduced during ischaemia. Furthermore, the response of ischaemic myocytes to cholinergic stimuli may be altered, as the function of inhibitory G-proteins mediated by muscarinic M2-receptors is reversibly impaired after short periods of ischaemia. This may lead to a reduction of the muscarinic receptor-mediated inhibition of AC and thereby contribute to ischaemia-induced arrhythmogenesis. Prevention of ischaemia-induced alterations in Gi-mediated signal transduction and/or (with certain limitations discussed below)-selective activation of cardiac muscarinic M2-receptors could therefore be an alternative pharmacological treatment for acute myocardial ischaemia.


[Spiral arrangement of muscular elements in the walls of blood vessels and their role in hemodynamics].
The article claims that contractions of the cardiac left ventricle produce a whirling (turbulent) movement of blood that is maintained in the aorta. In the walls of large and small arteries, as well as in the arteriolar walls, myocytes have a spiral arrangement. Their contraction maintains the turbulent blood stream in the vessels with a small diameter, in spite of the fact that the Reinolds' number for them is rather small. The author considers that while making a mathematical analysis of the blood flowing in the arteries, it is necessary to take into account that the walls of the arterial vessels actively influence the blood stream.


A self-healable, moldable and bioactive biomaterial gum for personalised and wearable drug delivery.
One of the long-standing challenges in materials science involves synthesizing biomaterials that recapitulate important features of native biological tissues. Even though, the number of available biomaterials at the moment are virtually limitless, few of them has unlocked all the secrets of the human body by mimicking the combinatorial-like material properties of our tissues and organs. Inspired by the human body, we have developed a polymeric gum, which combines stretchability, toughness, strength, flexibility, and self-healing. It also exhibits a high bioactivity that can target and eliminate bacterial infections fast and reliably. Notably, this material is moldable into almost any complex shape, and therefore suitable as a building block for wearables designed to conform directly with the curved and personalized anatomy of patients. It also exhibits excellent drug retention and release capacity, which altogether makes it suitable for applications in personalized wearable drug-delivery devices.


Educating Families of Children Newly Diagnosed With Cancer.
Parents/caregivers require specialized education in order to care for their child with a newly diagnosed cancer. Currently, no evidence-based guidelines exist to identify content essential for inclusion in patient/family education prior to a child's initial discharge home; this study used Delphi methodology to obtain multidisciplinary consensus regarding essential content amongst pediatric oncology experts from the Children's Oncology Group. Three questionnaire rounds were employed to identify essential content, evaluate the importance of the educational topics identified, and gain expert consensus regarding the final ranking of topics identified and whether or not each topic was considered mandatory for inclusion in education for newly diagnosed patients. Disease-specific topics were also identified for patients with leukemia, solid tumors, and central nervous system tumors. The results of this study provide, for the first time, multidisciplinary expert consensus regarding key content essential for inclusion in discharge education for newly diagnosed pediatric oncology patients.


Serotyping of Brunei pneumococcal clinical strains and the investigation of their capability to adhere and invade a brain endothelium model.
Pneumococcal infections have caused morbidity and mortality globally. Streptococcus pneumoniae (pneumococci) are commensal bacteria that colonize the nasopharynx, asymptomatically. From there, pneumococci can spread in the lungs causing pneumonia and disseminate in the bloodstream causing bacteremia (sepsis) and reach the brain leading to meningitis. Endothelial cells are one of the most important components of the blood-brain barrier that separates the blood from the brain and plays the first protective role against pneumococcal entry. Thus this study aimed to investigate on the ability of non-meningitis pneumococcal clinical strains to adhere and invade a brain endothelium model. Two pneumococcal Brunei clinical strains were serotyped by multiplex PCR method using oligonucleotide sequences derived from Centers for Disease Control and Prevention. A validated immortalised mouse brain endothelial cell line (bEnd.3) was used as a brain endothelium model for the study of the pneumococcal breach of the blood-brain barrier using an adherence and invasion assay. Both of the pneumococcal clinical strains were found to be serotype 19F, a common circulating serotype in Southeast Asia and globally and possess the ability to adhere and invade the brain endothelial cells. In addition, this is the first report on the serotype identification of pneumococci in Brunei Darussalam and their application on a brain endothelium model. Further studies are required to understand the virulence capabilities of the clinical strains.


Colfibrate attenuates blood pressure and sodium retention in DOCA-salt hypertension.
Clofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR alpha) agonist, increases renal tubular cytochrome P450 4a (Cyp4a) expression thereby increasing 20-hydroxyeicosatetraenoic acid (20-HETE) production. To determine if clofibrate affects blood pressure regulation we studied mice with DOCA-salt induced hypertension in wild-type and PPAR alpha knockout mice. Wild-type mice treated with DOCA-salt had higher mean arterial pressures and higher cumulative sodium balance, but lower renal 20-HETE production than did vehicle-treated mice. Treating DOCA-salt mice with clofibrate attenuated the increase in mean arterial pressure and cumulative sodium balance while increasing 20-HETE production and renal Cyp4a expression. In contrast the PPAR alpha knockout mice treated with clofibrate and DOCA-salt showed no attenuation in the increase of blood pressure, cumulative sodium balance, renal 20-HETE production or Cyp4a protein expression. Expression of the PPAR alpha protein was greater in proximal tubules than in renal microvessels. Our results show that PPAR alpha pathway induces renal tubular 20-HETE production which affects sodium retention and blood pressure regulation in DOCA-salt-treated mice.


Diabetes mellitus is associated with subnormal serum levels of free testosterone in men.
To evaluate the relationship between diabetes mellitus (DM) and serum levels of free (FT) and total (TT) testosterone. A cross-sectional study was carried out including 746 men, of whom 116 (15.6%) were diabetics. Both groups, diabetic and nondiabetic, were paired according to age. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated, and a stratification analysis correlating DM and elevated BMI (>25 kg/m(2)) and WHR (>1) with the presence of subnormal FT and TT levels was performed. FT and TT serum levels were subnormal in 46% and 34% of diabetics, respectively, and in 24% and 23% of nondiabetics. Subnormal FT levels were strongly correlated with DM (odds ratio (OR) 2.7; 95% confidence interval (CI) 1.8-4.1) but not with elevated BMI (OR 1.4; 95% CI 1.0-2.0). Subnormal TT levels were more strongly associated with elevated BMI and WHR (OR 2.6; 95% CI 1.7-3.9 and 2.0; 1.4-2.9) than with DM (1.7; 1.1-2.6 and 2.0; 1.3-3.2). These data strongly suggest that DM is associated with subnormal FT levels, and that TT levels are influenced more by obesity and central adiposity.


Introducing the scanning air puff tonometer for biological studies.
It is getting increasingly evident that physical properties such as elastoviscoplastic properties of living materials are quite important for the process of tissue development, including regulation of genetic pathways. Measuring such properties in vivo is a complicated and challenging task. In this paper, we present an instrument, a scanning air puff tonometer, which is able to map point by point the viscoelastic properties of flat or gently curved soft materials. This instrument is an improved version of the air puff tonometer used by optometrists, with important modifications. The instrument allows one to obtain a direct insight into gradients of material properties in vivo. The instrument capabilities are demonstrated on substances with known elastoviscoplastic properties and several biological objects. On the basis of the results obtained, the role of the gradients of elastoviscoplastic properties is outlined for the process of angiogenesis, limb development, bacterial colonies expansion, etc. which is important for bridging the gaps in the theory of the tissue development and highlighting new possibilities for tissue engineering, based on a clarification of the role of physical features in developing biological material.


Regulation of P2X7 receptor function of neural progenitor cells in the hippocampal subgranular zone by neuronal activity in the dentate gyrus.
P2X7 receptors (Rs) mediate apoptosis/necrosis in neuronal and non-neuronal systems. Patch-clamp recordings from dentate gyrus (DG) granule cells in acutely prepared hippocampal slices of mice showed that incubation with 4-aminopyridine (4-AP) causes an excitability increase. This led to an enhanced sensitivity of P2X7Rs of the underlying subgranular zone neural progenitor cells (NPCs) towards dibenzoyl-ATP (Bz-ATP). The glutamatergic agonists NMDA and AMPA, as well as the purinergic agonist ATP also increased the Bz-ATP-induced current amplitudes (IBzATP). Tetrodotoxin as well as the standard antiepileptic drugs phenytoin, valproic acid and gabapentin counteracted the effect of 4-AP, most likely by decreasing the firing rate and/or action potential duration of DG granule cells and in consequence the release of ATP/glutamate onto NPCs. Experiments with organotypic hippocampal slice cultures confirmed these results also under conditions when 4-AP was applied for longer time periods and at much lower concentrations than used in acute slices. It was concluded that pathological firing modelled by 4-AP might trigger a sensitivity increase of P2X7Rs leading to necrosis/apoptosis of NPCs with the subsequent decrease of NPC, and in consequence, granule cell number. Hence, supersensitive P2X7Rs may exert a beneficial counter-regulatory effect by reducing the chances for the evolution of chronic temporal lobe epilepsy by ectopically located granule cells.


Statistical considerations in identifying mechanisms of change.
The statistical search for mechanisms of change involves multiple inferential tests, ones that generally follow a fixed sequence designed to demonstrate mediation. While there are several popular approaches to conducting such tests, e.g., SEM and MRA, the inflated Type I error rate problem associated with conducting these tests has received little, if any, attention. This paper offers 2 solutions to avoid committing Type I errors associated with mediational tests. Most straightforward, investigators may choose to use a Bonferroni adjustment. In contrast, a design-based approach can be used that tests rival explanations for the observed effects. Examples drawn from addiction research are provided.


Influence of prenatal ethanol exposure on vascular contractile response in rat thoracic aorta.
Fetal alcohol syndrome is associated with cardiovascular malformation. However, the impact of prenatal ethanol exposure on vascular function is not clear. The purpose of this study was to examine the influence of prenatal ethanol exposure on vascular response in adulthood. Timed-pregnancy, female rats were fed an ethanol-containing liquid diet (36% calorically or 6.36% [vol./vol.]) or control diet from gestation day 2 until labor. The pups continued to receive a standard rat chow through adulthood, and the force-generating capacity of aortic ring segments was examined. Prenatal ethanol exposure did not significantly affect postnatal growth, but it did lead to elevated blood pressure in adulthood. The contractile response to potassium chloride was similar in vessels with intact endothelium, although the median effective concentration (EC(50)) was significantly reduced by prenatal ethanol exposure in rings with denuded endothelium. The response to norepinephrine was attenuated by prenatal ethanol exposure in rings with either intact or denuded endothelium. The endothelium-dependent relaxation to carbamylcholine chloride was significantly attenuated by prenatal ethanol exposure. Vasorelaxant response to the nitric oxide donor sodium nitroprusside or beta-adrenergic agonist isoproterenol was similar between control and prenatal-ethanol-exposed groups with either intact or denuded endothelium. Ethanol elicited a dose-dependent endothelium-dependent vasorelaxation, which was comparable between the two animal groups. The ethanol-induced endothelium-dependent vasorelaxation was attenuated by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester. These findings seem to indicate that prenatal ethanol exposure contributes to alterations of both endothelium-dependent and endothelium-independent vascular contractile responses.


Reactivity of surface alkoxy species on acidic zeolite catalysts.
[Reaction: see text]. A solid understanding of the mechanisms involved in heterogeneously catalyzed reactions is of fundamental interest for modern chemistry. This information can help to refine modern theories of catalysis and, in a very practical way, can help researchers to optimize existing industrial processes and develop new ones. To understand the mechanisms of heterogeneous catalysis, we need to observe and identify reaction intermediates on a working catalyst. Motivated by this goal, we have monitored the catalytic events in heterogeneous systems using in situ magic-angle-spinning (MAS) NMR under flow conditions. In this Account, we describe the reactivity and possible intermediate role of surface alkoxy species in a variety of zeolite-catalyzed reactions. First, we isolate the surface alkoxy species on a working zeolite catalyst and then investigate the chemical reactivity with different probe molecules under reaction conditions. Finally, we investigate reaction mechanisms facilitated by these intermediate surface alkoxy species. We examined the reactivity of surface methoxy species (SMS) in terms of C-O bond and C-H bond activation. SMS on acidic zeolite catalysts act as an effective methylating agent when reacted with different probe molecules (including methanol, water, ammonia, alkyl halides, hydrochlorides, aromatics, carbon monoxide, and acetonitrile) through C-O bond activation. At higher reaction temperatures (ca. 523 K and above), the C-H bond activation of SMS may occur. Under these conditions, intermediates such as surface-stabilized carbenes or ylides are probably formed. This C-H bond activation is directly related to the initiation mechanism of the methanol-to-olefin (MTO) process and invites further investigation. Based on our experimental results, we also discuss the reactivity and the carbenium-ion-like nature of surface alkoxy species and recent theoretical investigations in this area.


Branching, flowering and fruiting of Jatropha curcas treated with ethephon or benzyladenine and gibberellins.
Jatropha curcas L. has been identified for biofuel production but it presents limited commercial yields due to limited branching and a lack of yield uniformity. The objective of this study was to evaluate the effects of single application of ethephon or a combination of 6-benzyladenine (BA) with gibberellic acid isomers A4 and A7 (GA4+7) on branch induction, flowering and fruit production in jatropha plants with and without leaves. Plants with and without leaves showed differences for growth and reproductive variables. For all variables except inflorescence set, there were no significant statistical interactions between the presence of leaves and plant growth regulators concentration. The total number of flowers per inflorescence was reduced as ethephon concentration was increased. As BA + GA4 +7 concentration increased, seed dry weight increased. Thus, ethephon and BA + GA4 +7 applications appeared to affect flowering and seed production to a greater extent than branching. The inability to discern significant treatment effects for most variables might have been due to the large variability within plant populations studied and thus resulting in an insufficient sample size. Therefore, data collected from this study were used for statistical estimations of sample sizes to provide a reference for future studies.


Availability of health-promoting interventions in high schools in Quebec, Canada, by school deprivation level.
School-based health-promoting interventions (HPIs) foster adolescent health and well-being. Access to HPIs may differ by the socioeconomic advantage of students at each school (school deprivation). We assessed the importance of health issues and availability of HPIs and extracurricular activities by school deprivation in high schools in Quebec, Canada. In 2016/17, 2017/18 and 2018/19, we interviewed school principals or a designee in 48 public high schools classified as disadvantaged (33%) or advantaged (67%). Schools rated whether 13 common health-related issues were important (i.e. warranted intervention) in their student population and reported whether HPIs to address these or other health issues and/or sports or special interest extracurricular activities had been available in the past year. 84% of disadvantaged schools offered one or more HPIs in the past year compared to 73% of advantaged schools. Higher proportions of disadvantaged schools perceived most of 13 health-related issues as important. HPIs for bullying/exclusion, sex education and physical activity (issues subject to government mandates) were available in most schools. Higher proportions of disadvantaged schools offered non-mandated HPIs (i.e. for healthy eating, mental health/well-being and substance use). Higher proportions of advantaged schools offered extracurricular activities in all areas other than non-competitive sports, which was offered by equal proportions of advantaged and disadvantaged schools. Government mandates appear to facilitate universal availability of HPIs in schools, possibly boosting equity in school-based health promotion. Further investigation of possible differences in the content, implementation and/or effects of HPIs based on school deprivation is warranted.


Reproducibility Study of the Thermoplastic Resin Transfer Molding Process for Glass Fiber Reinforced Polyamide 6 Composites.
Polyamide 6 (PA6) thermoplastic composites have higher recyclability potential when compared to conventional thermoset composites. A disruptive liquid molding manufacturing technology named Thermoplastic Resin Transfer Molding (T-RTM) can be used for processing composites due to the low viscosity of the monomers and additives. In this process, polymerization, crystallization and shrinkage occur almost at the same time. If these phenomena are not controlled, they can compromise the reproducibility and homogeneity of the parts. This work studied the influence of packing pressure, as a process variable, throughout the filling and polymerization stages. To assess the process reproducibility and parts' homogeneity, physical, thermal and mechanical properties were analyzed in different areas of neat PA6 and composite parts. This study showed that a two-stage packing pressure can be successfully used to increase parts' homogeneity and process reproducibility. The use of 3.5 bar packing pressure during the polymerization stage resulted in mechanical properties with lower standard deviations, indicating a higher degree of homogeneity of the manufactured parts and higher process reproducibility. These results will be used for establishing the actual state of the technology and will be a base for future process optimization.


Oral treatment for Mycobacterium ulcerans infection: results from a pilot study in Benin.
Mycobacterium ulcerans infection is responsible for severe skin lesions in sub-Saharan Africa. We enrolled 30 Beninese patients with Buruli ulcers in a pilot study to evaluate efficacy of an oral chemotherapy using rifampicin plus clarithromycin during an 8-week period. The treatment was well tolerated, and all patients were healed by 12 months after initiation of therapy without relapse.


Medication regimen complexity of coronary artery disease patients.
To determine the factors associated with the high complexity of medication regimen in patients with coronary artery disease. A cross-sectional study was carried out in a multiprofessional cardiology outpatient clinic, in the Secondary Care of the Unified Health System, where sociodemographic (age, sex, and education), clinical (number of health conditions, cardiovascular diagnoses, and comorbidities) and pharmacotherapeutic (adherence, polypharmacy, and cardiovascular polypharmacy) characteristics were collected. These were related to complexity of medication regimen, measured through the medication regimen complexity index. The classification of high complexity of medication regimen was carried out using standardization for the older adults and stratification for adult patients, as suggested in the literature. The total complexity medication regimen of 148 patients had a median of 17.0 (interquartile range of 10.5). In the univariate analysis, the factors associated with high complexity were heart failure, diabetes mellitus, hypertension, five or more diseases, and non-adherence to treatment. In the final model, after logistic regression, there was a statistically significant association (p<0.05) with the variables diabetes mellitus, hypertension, and non-adherence. The high complexity of medication regimen in patients with coronary artery disease was associated with the presence of diabetes mellitus, hypertension, and reports of non-adherence to treatment.


Somatic function, mental health and psychosocial functioning in 22 adolescents with bladder exstrophy and epispadias.
We report the long-term somatic outcome, mental health and psychosocial adjustment in adolescents with bladder exstrophy and epispadias. A total of 22 adolescents 11 to 20 years old (median age 14.5), including 19 with bladder exstrophy and 3 with epispadias, were assessed for urogenital status, stoma, renal and bowel function, anorectal physiology, mental health and psychosocial functioning by physical examinations, semistructured interviews and standardized questionnaires. The parents of 21 patients were interviewed and completed questionnaires. Information was also obtained on control groups. Of the 22 patients 9 (41%) had no urinary diversion and were urinary incontinent, 6 (27%) had persistent fecal staining and anal canal pressures that were lower than the controls, 10 (59%) were dissatisfied with the penile appearance and 11 (50%) met the criteria for psychiatric diagnoses. The main predictors of mental health were parental warmth and patient genital appraisal in the 11 to 14-year age group, and parental warmth and urinary continence function in the 15 to 20-year age group. Psychosocial dysfunction was predicted by fecal incontinence in the younger group and worries about future sexual relationships in the older group. The present multimodal outcome study revealed that adolescents with bladder exstrophy and epispadias had significant physical and mental problems. Genital malformation, and urinary and fecal incontinence may have a negative impact on mental health and psychosocial functioning. Our findings emphasize the need to include psychosocial experts on health care teams to reveal the amount of distress caused by these anomalies and to offer psychosocial support.


Watermelon stomach in end-stage renal disease patient.
Gastric antral vascular ectasia (GAVE), also called watermelon stomach, is a rare cause of gastrointestinal (GI) bleeding. GAVE is associated with a number of conditions, including portal hypertension, chronic kidney disease (CKD), and collagen vascular diseases, especially scleroderma. Limited reports of GAVE are present in CKD patients. Argon plasma coagulation (APC) is an effective therapy for GAVE. We describe the case of a CKD, stage V patient, who presented with recurrent blood loss in stools and transfusion-dependent anemia. Her endoscopy revealed GAVE, which was managed uneventfully with APC.


Interrelationships among gekkonid geckos inferred from mitochondrial and nuclear gene sequences.
Gekkonid geckos, representing more than 85 percent of the gekkotan genera, are found on all major land masses and almost all oceanic islands in the tropics and subtropics. Intergeneric relationships of the Gekkonidae have been far more difficult to resolve than those among other gekkotan families. Our data set consists of a large number of complete mitochondrial 12S rRNA gene sequences and partial nuclear C-mos gene sequences for 33 genera of geckos, two genera of pygopods and two genera of eublepharids. Maximum parsimony (MP) and maximum likelihood (ML) trees were generated based on unweighted analysis using PAUP 4.0b10. Bayesian inference (BI) analyses trees were generated by MrBayes 3.0B4. All phylogenetic trees supported the monophyly of Gekkonidae with great confidence. The 12S data and combined data (12S and C-mos) place Sphaerodactylus deeply within gekkonine geckos, whereas Teratoscincus+Pristurus are the sister group of the remaining gekkonids. However, it is known that 12S may be positively misleading when dealing with older divergences. Therefore, the conflict between the results in this study and the latest conclusions based on C-mos points to the need for future focus on the phylogenetic position of both Sphaerodactylus and Teratoscincus.


Implementation of an elective wellness course.
In an effort to increase knowledge and attitudes toward promoting health rather than treating disease, faculty in one school developed an elective wellness course open to all university students. The authors discuss how students learned concepts of wellness and developed individualized plans to improve their own health status.


Phase diagram of a square-shoulder, square-well fluid revisited.
We report here the phase diagrams for a model square-shoulder, square-well fluid obtained by histogram reweighting Monte Carlo simulations. The critical points corresponding to the gas-liquid condensation and to the liquid-liquid transition have been located. Also, we have estimated the temperatures and densities at the triple points. We believe that our results are more precise and complete than those published so far.


Roles of the first and second round of DNA replication in the regulation of zygotic gene activation in mice.
In the mouse embryo, expression of zygotic genes starts in the S/G2 phase of the 1-cell stage and greatly increases during the 2-cell stage. Although the timing of zygotic gene activation (ZGA) is thus established, the mechanism regulating ZGA is poorly understood. Previous studies using reporter genes have suggested that a transcriptionally repressive state is established during the 2-cell stage and that the first and second rounds of DNA replication are involved in this process. To further elucidate the respective roles of the two rounds of DNA replication in ZGA, we analyzed the expression of four ZGA genes (hsp70.1, eif-1a, muerv and zscan4d) in embryos whose DNA replication was inhibited by treatment with aphidicolin, an inhibitor of DNA polymerase. Inhibiting the first round increased the expression levels of hsp70.1, eif-1a and zscan4d but decreased that of muerv, while inhibiting the second round increased the expression levels of all four genes. These results suggest that the transcriptionally repressive state seems to be established after the second round of DNA replication.


Surgical Lymphadenectomy: The Impact of Sentinel Node Mapping in Breast Cancer.
Lymphatic mapping continues to grow in utility both as a diagnostic aid and as a method for performing less morbid, potentially therapeutic lymphadenectomies. Its use in breast cancer has become the standard of care for staging and sentinel lymph node dissection is considered sufficiently therapeutic for low-volume axillary disease. Lymphatic mapping has re-emphasized the importance of adequate lymphatic staging both in terms of the amount of lymph nodes resected and the amount of each lymph node that is assessed. Going forward, these concepts continue to be adopted into other tumors, with active investigations ongoing in gastrointestinal cancers, head and neck cancers, and gynecologic cancers.


Cu(NO3)2.3H2O-mediated synthesis of 4'-(2-pyridyl)-2,2':6',2' '-terpyridine (L2) from N-(2-pyridylmethyl)pyridine-2-methylketimine (L1). A C-C bond-forming reaction and the structure of {[Cu(L2)(OH)(NO3)][Cu(L2)(NO3)2]}.2H2O.
N-(2-Pyridylmethyl)pyridine-2-methylketimine (L1) was synthesized from equimolar quantities of (2-pyridyl)methylamine and 2-acetylpyridine. Methanolic solution of L1 reacted readily with Cu(NO3)2.3H2O in air, affording green solid of composition {[Cu(L2)(OH)(NO3)][Cu(L2)(NO3)2]}.2H2O, where L2 is 4'-(2-pyridyl)-2,2':6',2' '-terpyridine. Oxidation of the active methylene group of L1 to an imide and then condensation with 2-acetylpyridine involving a C-C bond-forming reaction, mediated by a Cu2+ ion, are the essential steps involved in the conversion of L1 to L2. L2 is isolated by extrusion of Cu2+ with EDTA(2-). The copper center in [Cu(L2)(OH)(NO3)] has a mer-N3O3 environment, and that in [Cu(L2)(NO3)2] has a distorted trigonal-bipyramidal geometry. Two H2O molecules held by C-H...O interactions are present in the predominantly hydrophobic channels of approximate cavity dimension 7.60 x 6.50 A created by aromatic rings through pi-pi interactions.


Butyrate enhances intestinal epithelial barrier function via up-regulation of tight junction protein Claudin-1 transcription.
Barrier function is essential for the maintenance of normal intestinal function. Dysregulation of the intestinal barrier underlies a wide range of disorders. Previously, we found that sodium butyrate (NaB) decreased the molecular permeability of intestinal barrier in vivo model, but the mechanism by which NaB facilitated the tightness of tight junctions (TJs) in small intestinal epithelium needed further studies. In vitro culture of the cdx2-IEC monolayer was used to mimic barrier function. The TJs were assessed by transepithelial electrical resistance (TEER) and paracellular flux of fluorescein isothiocyanate-conjugated dextran 40,000 (FD-40), Western blot, Q-RT-PCR, and immunofluorescence. Promoter and chromatin immunoprecipitation (ChIP) assays were also done to analyze the Claudin-1 gene. NaB decreased FD-40 flux, increased TEER and TJ protein Claudin-1 expression, induced ZO-1 and Occludin redistribution in cellular membrane, and reversed the damage effect after calcium (Ca(2+)) switch assay. Silencing Claudin-1 prevented protective function of NaB from enhancing intestinal barrier integrity. Further studies demonstrated that NaB increased Claudin-1 transcription by facilitating the interaction between transcription factor SP1 and a specific motif within the promoter region of Claudin-1. This SP1 binding motif was located upstream of the coding region (-138 to -76 bp) and indispensable for the transcription of Claudin-1 following NaB treatment. ChIP assay confirmed the association between SP1 and Claudin-1 promoter, and the elimination of the SP1 binding site by point mutation resulted in a significant loss of Claudin-1 transcription after NaB dealing. NaB enhanced intestinal barrier function through increasing Claudin-1 transcription via facilitating the association between SP1 and Claudin-1 promoter.


BMP-7 PROTEIN EXPRESSION IS DOWNREGULATED IN HUMAN DIABETIC NEPHROPATHY.
Bone morphogenetic protein-7 (BMP-7) is expressed in all parts of the normal kidney parenchyma, being highest in the epithelium of proximal tubules. It protects kidney against acute and chronic injury, inflammation and fibrosis. Diabetic nephropathy is the leading cause of chronic kidney disease, and is characterized by decreased expression of BMP-7. The aim of our study was to analyze whether the expression of BMP-7 is significantly changed in advanced stages of human diabetic nephropathy. Immunohistochemical analysis of the expression of BMP-7 was performed on archival material of 30 patients that underwent renal biopsy and had confirmed diagnosis of diabetic nephropathy. Results showed that BMP-7 was differently expressed in the cytoplasm of epithelial cells of proximal tubules and podocytes among all stages of diabetic nephropathy. At early stages of diabetic nephropathy, BMP-7 was strongly positive in proximal tubules and podocytes, while low expression was recorded in the majority of samples at advanced stages. In conclusion, increased expression of BMP-7 at initial stages of diabetic nephropathy with subsequent decrease at advanced stage highlights the role of BMP-7 in the protection of kidney structure and function. Further investigations should be focused on disturbances of BMP-7 receptors and signaling pathways in patients with diabetic nephropathy.


Health action to meet contemporary challenges.
While India has made rapid strides in building its medical manpower and medical service, yet many of the major health problems are far from being controlled. Although earlier Health problems have not been resolved, newer threats to health through misguided development are getting superadded. The major health threats today are the denial of minimal sustenance base, such as adequate food and water to an increasing number of people. The rapidly increasing uncontrolled chemicalization of body and environment is another health hazard. Experience has shown that health needs cannot be satisfied merely by expansion of the medical industry. Health care work would have to involve an attempt to arrest the growing threats to health and survival, and rebuilding of the ecological base, to ensure provision of basic needs to all. These efforts would be towards a new economics, because they include radical shifts in food agriculture policy, resources use policy, industrial policy etc and can only be guided by a deep sense of social justice and human concern. Contemporary health care work has increasingly to involve those who are already looking for alternatives e.g., those involved in ecology movements, feminist movement, peace and civil rights groups, those involved in alternative education, agriculture, health care journalism. Priority has to be given and strategies evolved to help add a health dimension, to various health or non health work and initiatives already existing, with a special effort to safeguard the traditional health care knowledge systems from total disintegration. Grass root level feed back should constitute an essential pre-requisite for any (health) policy formulation and its implementation.


Acute human immunodeficiency virus type 1 disease as a mononucleosis-like illness: is the diagnosis too restrictive?
The purpose of this study was to describe the frequency and duration of clinical features at the time of acute human immunodeficiency virus type 1 (HIV-1) disease in 218 patients with documented symptomatic primary HIV-1 infection. The mean duration of acute HIV-1 disease was 25.1 days (median, 20.0 days) and did not differ by gender, age, and risk factor. The frequency and mean duration of clinical features occurring in >50% of patients were as follows: fever, 77.1% and 16.9 days; lethargy, 65.6% and 23.7 days; cutaneous rash, 56.4% and 15 days; myalgia, 54.6% and 17.7 days; and headache, 50.9% and 25.8 days. Only 15.6% of patients presented with a typical mononucleosis-like illness (MLI) defined as fever, pharyngitis or sore throat, and cervical adenopathy, and 10% had no features of an MLI. A meningitis-like syndrome occurred in 20 patients (9.2%). Acute HIV-1 disease is more diverse than previously reported, and the absence of fever or other MLI features does not rule out acute HIV-1 disease.


Cis-effects on gene expression in the human prenatal brain associated with genetic risk for neuropsychiatric disorders.
The majority of common risk alleles identified for neuropsychiatric disorders reside in noncoding regions of the genome and are therefore likely to impact gene regulation. However, the genes that are primarily affected and the nature and developmental timing of these effects remain unclear. Given the hypothesized role for early neurodevelopmental processes in these conditions, we here define genetic predictors of gene expression in the human fetal brain with which we perform transcriptome-wide association studies (TWASs) of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, bipolar disorder, major depressive disorder, and schizophrenia. We identify prenatal cis-regulatory effects on 63 genes and 166 individual transcripts associated with genetic risk for these conditions. We observe pleiotropic effects of expression predictors for a number of genes and transcripts, including those of decreased DDHD2 expression in association with risk for schizophrenia and bipolar disorder, increased expression of a ST3GAL3 transcript with risk for schizophrenia and ADHD, and increased expression of an XPNPEP3 transcript with risk for schizophrenia, bipolar disorder, and major depression. For the protocadherin alpha cluster genes PCDHA7 and PCDHA8, we find that predictors of low expression are associated with risk for major depressive disorder while those of higher expression are associated with risk for schizophrenia. Our findings support a role for altered gene regulation in the prenatal brain in susceptibility to various neuropsychiatric disorders and prioritize potential risk genes for further neurobiological investigation.


Changes of desmin expression pattern in the myocardium of patients with alcoholic dilated cardiomyopathy.
It has been suggested that desmin cytoskeleton remodeling may contribute to the progression of dilated cardiomyopathy and might affect long-term prognosis. This study is aiming at evaluating desmin expression in cardiomyocytes from patients with dilated cardiomyopathy of alcoholic etiology in advanced stages of the disease and comparing the results with measurements of normal heart tissue from control patients. For immunohistochemistry, sections from 36 myocardium fragments taken from left ventricle of dilated cardiomyopathy patients were immunolabeled with an anti-desmin antibody and negative control slides were obtained by omitting the primary antibody. We calculated the ratios between the areas of myocardiocytes and the length and number of A dark disks and assessed the desmin expression level as the integrated optical density (IOD) and, respectively, the total areas of the signal given by immunolabeling. A Student's t-test has been utilized to assess the differences, p<0.05 deemed significant data. We identified significant decrease in numerical density of dark disks in our cases group compared with controls (p<0.05). Also, the ratios between total cellular area and total length of dark disks and number of dark disks was significantly different between cases and controls (p=0.04). IOD was significantly different between dilative cardiomyopathy cases and controls and also, overall desmin expression area was increased in dilatative cardiomyopathy patients. The identification of different desmin expression and standardization in diseased myocardium may be helpful in stratifying patients and in understanding their evolution, but also in finding new therapeutic targets that aim the alterations in desmin expression.


Use of a Soft Silicone Foam Dressing to Change the Trajectory of Destruction Associated with Suspected Deep Tissue Pressure Ulcers.
To explore the evolution of suspected deep tissue injury (sDTI) pressure ulcers and identify the role of early identification and intervention in hindering tissue destruction. In contrast to previously published evidence, the foundational research identified a significant trend of sDTI recovery which warranted further analysis. A single-site, 24-month retrospective, IRB-approved study evaluated 77 adult (age 18 or older) hospitalized subjects with 128 wound care nurse-identified sDTIs over the course of 1 day to 14 weeks for 377 encounters. Data from a 24-month period (2010-2012) were analyzed during the primary study. In addition to demographics, the evolution process including site, initial presentation, measurements, tissue consistency, and treatment, were assessed. In response to findings of significant sDTI recovery, a secondary in-depth analysis focused on commonalities and variables for clarity of their contribution to the isolated improved patient outcomes. In addition to clearer delineation of demographics, co-morbid conditions, and evolutionary patterns, the researcher identified patient outcomes in stark contrast to those previously published in the literature. A significant outcome of resolution of sDTI pressure ulcers was observed. Upon further review, the role of absorbent soft silicone, multi-layer, self-adherent bordered foam (Mepilex) in these outcomes was elucidated clearly.


Impact of lactational performance on bone mineral density in marginally-nourished Bangladeshi women.
This cross-sectional study, carried out during July 1997-June 1998, evaluated the effects of prolonged breast-feeding and lactational amenorrhoea on bone mineral density (BMD) in 400 marginally-nourished Bangladeshi women aged 20-81 years. A bone densitometer was used for measuring BMD in the distal and ultra-distal end of radius and ulna. The results showed that the women who breastfed for 60 months or less had a higher mean BMD compared to those who breastfed for 61-120 months and for over 120 months. There was a significantly higher BMD in the women who had a shorter duration of lactational amenorrhoea compared to those having a longer duration of lactational amenorrhoea. BMD was significantly and negatively correlated with total duration of lactational amenorrhoea (slope -0.024, p<0.05) after controlling for parity, physical workload, and total duration of breast-feeding. The study concluded that there was a negative correlation between longer duration of breast-feeding and BMD, but it was not found when other factors were controlled in multivariate analysis. The duration of lactational amenorrhoea, which is a proxy indicator of breast-feeding, showed a negative correlation with BMD. It is recommended that all lactating women be given diet with adequate calcium to support breast-feeding for maintaining good nutrition of their bones.


Controlled sparse and percolating cross-linking in waterborne soft adhesives.
The effect of low levels of cross-linking on the adhesive and mechanical properties of waterborne pressure-sensitive adhesives was investigated. We have taken advantage of a core-shell latex particle morphology obtained by emulsion polymerization to create a heterogeneous structure of cross-links without major modification of the monomer composition. The latex particles comprise a shell containing cross-linkable diacetone acrylamide (DAAM) repeat units localized on the periphery of a slightly softer core copolymer of very similar composition. Adipic acid dihydrazide was added to the latex prior to film formation to react with DAAM repeat units and affect interfacial cross-linking between particles in the adhesive films. The honeycomb-like structure obtained after drying of the latex results in a good balance between the dissipative properties required for adhesion and the resistance to creep. The characterization of the mechanical properties of the films shows that the chosen cross-linking method creates a percolating lightly cross-linked network, swollen with a nearly un-cross-linked component. With this cross-linking method, the linear viscoelastic properties of the soft films are nearly unaffected by the cross-linking while the nonlinear tensile properties are greatly modified. As a result, the long-term shear resistance of the adhesive film improves very significantly while the peel force remains nearly the same. A simple rheological model is used to interpret qualitatively the changes in the material parameters induced by cross-linking.


Asymmetry of Edema Formation: The Possibility of a Somatic Mosaic.
A 57-year-old woman experienced an abnormal feeling on the left side of her neck and difficulty breathing 90 minutes after eating Chinese noodles. She had a history of removal of a left sphenoid ridge meningioma one year earlier. She had experienced rigidity of her left neck and peripheral cold sensation on her left side in winter since approximately 10 years of age. She had experienced peripheral swelling of her left side and lower back pain of unknown origin on her left side several times. She had suffered for oral allergy syndrome since she was young. She sometimes experienced a tingling sensation on her lips and an unpleasant feeling in her throat after eating some types of fruit. On arrival, 180 minutes after eating the noodles, she had clear consciousness and stable vital signs. She had left neck and chest swelling without color change. Her difficulty breathing subsided spontaneously. A blood analysis revealed an increased level of immunoglobulin E. Neck computed tomography (CT) with contrast medium and magnetic resonance imaging (MRI) revealed left-side-limited edema in the subcutaneous area and surrounding esophagus and bronchus. These radiological findings denied hemorrhaging or pseudoaneurysmal formation. She underwent observational admission. After her edema improved, she was discharged on the third hospital day. A follow-up examination one week later showed the complete resolution of the neck and chest edema. A blood allergen test did not reveal the cause of the edema. The mechanism underlying the asymmetric transient edema after eating in the present case may involve somatic mosaic.


Adsorption and charge transfer dynamics of bi-isonicotinic acid on Au(111).
The interaction of bi-isonicotinic acid (4,4(')-dicarboxy-2,2(')-bipyridine) with the Au(111) surface has been investigated using electron spectroscopic techniques. Near edge x-ray absorption fine structure (NEXAFS) spectra show that monolayers of the molecule lie flat to the surface and also reveal that the monolayer is sensitive to the preparation conditions employed. Core level x-ray photoelectron spectroscopy (XPS) shows that the adsorbed molecule does not undergo deprotonation upon adsorption. The "core-hole clock" implementation of resonant photoemission has been used to probe the coupling between molecule and substrate. This technique has revealed the possibility of ultrafast backtransfer from the substrate into the molecule upon resonant excitation of a N 1s core level electron. This is supported by a NEXAFS and XPS investigation of energy level alignments in the system.


Distinguishing N-oxide and hydroxyl compounds: impact of heated capillary/heated ion transfer tube in inducing atmospheric pressure ionization source decompositions.
In the pharmaceutical industry, a higher attrition rate during the drug discovery process means a lower drug failure rate in the later stages. This translates into shorter drug development time and reduced cost for bringing a drug to market. Over the past few years, analytical strategies based on liquid chromatography/mass spectrometry (LC/MS) have gone through revolutionary changes and presently accommodate most of the needs of the pharmaceutical industry. Among these LC/MS techniques, collision induced dissociation (CID) or tandem mass spectrometry (MS/MS and MS(n)) techniques have been widely used to identify unknown compounds and characterize metabolites. MS/MS methods are generally ineffective for distinguishing isomeric compounds such as metabolites involving oxygenation of carbon or nitrogen atoms. Most recently, atmospheric pressure ionization (API) source decomposition methods have been shown to aid in the mass spectral distinction of isomeric oxygenated (N-oxide vs hydroxyl) products/metabolites. In previous studies, experiments were conducted using mass spectrometers equipped with a heated capillary interface between the mass analyzer and the ionization source. In the present study, we investigated the impact of the length of a heated capillary or heated ion transfer tube (a newer version of the heated capillary designed for accommodating orthogonal API source design) in inducing for-API source deoxygenation that allows the distinction of N-oxide from hydroxyl compounds. 8-Hydroxyquinoline (HO-Q), quinoline-N-oxide (Q-NO) and 8-hydroxyquinoline-N-oxide (HO-Q-NO) were used as model compounds on three different mass spectrometers (LCQ Deca, LCQ Advantage and TSQ Quantum). Irrespective of heated capillary or ion transfer tube length, N-oxides from this class of compounds underwent predominantly deoxygenation decomposition under atmospheric pressure chemical ionization conditions and the abundance of the diagnostic [M + H - O](+) ions increased with increasing vaporizer temperature. Furthermore, the results suggest that in API source decompostion methods described in this paper can be conducted using mass spectrometers with non-heated capillary or ion transfer tube API interfaces. Because N-oxides can undergo in-source decomposition and interfere with quantitation experiments, particular attention should be paid when developing API based bioanalytical methods.


Fighting Liver Fibrosis with Naturally Occurring Antioxidants.
Liver fibrosis is a wound-healing response characterized by the accumulation of extracellular matrix following various liver injuries, which results in the deformation of the normal liver architecture and the development of liver cirrhosis and even hepatocellular carcinoma. Numerous in vitro and in vivo studies indicated that oxidative stress mediates the initiation and progression of liver fibrosis. Overaccumulation of reactive oxygen species disrupts macromolecules, induces necrosis and apoptosis of hepatocytes, stimulates the production of pro-fibrogenic mediators, and directly activates hepatic stellate cells, thereby resulting in liver damage and initiating liver fibrosis. Ameliorating oxidative stress is a potential therapeutic strategy for the treatment of liver fibrosis. Natural antioxidants have attracted increasing attention in treating liver fibrosis due to their safety and efficacy. In this review, the pathogenesis of liver fibrosis and the role of oxidative stress in liver fibrosis were discussed. Naturally occurring antioxidants that can treat and prevent liver fibrosis were summarized. Advances in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of oxidative stress in liver fibrosis to representative antioxidants for treating liver fibrosis. Naturally occurring antioxidants show a potential for further investigations as lead compounds in fighting liver fibrosis.


Botulinum toxin injection as primary treatment for esotropia in patients with cerebral palsy.
Botulinum toxin type A is a potent neurotoxin that blocks the release of acetylocholine at the neuromuscular junction of cholinergic nerves. Cerebral palsy is cause of ocular disorders. There is an increased presence of strabismus, refractive errors, and reduced visual acuity. The purpose of this study was to assess the efficacy of botulinum toxin injection in the treatment of esotropia in patients with cerebral palsy. Seven patients were included in the study. All patients had a full ophthalmic examination on initial visit, including cycloplegic refraction and duction. The angle of esotropic deviation at distance was recorded in prism diopters. The botulinum toxin type A was administered into the medial rectus muscle under general anesthesia. Mean age of the patients was 12 years. The mean angle of deviation pretreatment was 36.6 PD. Successful motor alignment (orthotropia +/- 10 PD) was achieved in the botulinum toxin type A group in 57.1% of patients. The use of botulinum toxin in the treatment of esotropia in children and adolescents with cerebral palsy is an alternative to conventional surgical therapy.


Correlation Between Violence and Antipsychotic Dosage in Schizophrenia: A Secondary Analysis of The Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) Dataset.
Violent behavior is more common in individuals with schizophrenia, compared to the general population. Studies suggest higher psychotic symptoms are predictive of greater violent behavior. On the other hand, violent behaviors are reduced with antipsychotic treatment. However, the relationship between antipsychotic dosage and violence has not been studied to date. Thus, we aimed to determine if there exists an association between antipsychotic dosage and violence scores and whether the maximum violence would be predictive of the final antipsychotic dosage. We hypothesized that the violence scores at the final assessment in the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) would be correlated with the corresponding drug dosage and the maximum violence severity score would be predictive of the final dosage. Antipsychotic dosage at the end of the trial was converted into defined daily dosage and chlorpromazine equivalents (CPZe). Final and maximum violence sum scores were analyzed from the final violence assessment interviews. Spearman's rank-order correlation and linear regression analyses were used to analyze the relationship between the violence scores and standardized antipsychotic dosages. The analysis was on 952 individuals with schizophrenia. There was a significant association between maximum violence severity score and the final CPZe dosage (p=0.049). Exploratory analysis of age and ethnicity revealed younger non-white individuals to be at a higher risk of engaging in violent activities. Violence in schizophrenia is associated with poor illness course. Further studies focusing on violence in younger non-white individuals are warranted.


Prevalence of serum N-methyl-D-aspartate receptor autoantibodies in refractory psychosis.
N-methyl-d-aspartate receptor (NMDA-R) autoantibodies have been reported in people with acute psychosis. We hypothesised that their presence may be implicated in the aetiology of treatment-refractory psychosis. We sought to ascertain the point prevalence of NMDA-R antibody positivity in patients referred to services for treatment-refractory psychosis. We found that 3 (7.0%) of 43 individuals had low positive NMDA-R antibody titres. This suggests that NMDA-R autoantibodies are unlikely to account for a large proportion of treatment-refractory psychosis.


World Checklist of Opiliones species (Arachnida). Part 1: Laniatores - Travunioidea and Triaenonychoidea.
Comprising more than 6500 species, Opiliones is the third most diverse order of Arachnida, after the megadiverse Acari and Araneae. The database referred here is part 1 of 12 of a project containing an intended worldwide checklist of species and subspecies of Opiliones as Darwin Core archives, and it includes the superfamilies Travunioidea and Triaenonychoidea. These two superfamilies are often treated together under the denomination of Insidiatores. In this Part 1, a total of 571 species and subspecies are listed. Briggsidae and Cladonychiidae are both downgraded to subfamilies of Travuniidae. Peltonychia Roewer, 1935 is an available name and senior synonym of Hadziana Roewer, 1935 and is herein revalidated. Seven genera of Triaenonychidae described by Lawrence between 1931 and 1933 originally failed to comply ICZN rules for availability (Art. 13.3). All of them only became available when Staręga (1992) designated a type species for each. Therefore, the correct authorships of Austromontia Lawrence, 1931, Biacumontia Lawrence, 1931, Graemontia Lawrence, 1931, Larifugella Lawrence, 1933, Mensamontia Lawrence, 1931, Monomontia Lawrence, 1931 and Rostromontia Lawrence, 1931 are all Staręga, 1992. Fumontana Shear, 1977, originally referred only to subfamily Triaenonychinae (as opposed to Soerensenellinae then and not corresponding to present Triaenonychinae), not to any tribe (which in turn correspond to modern subfamilies) is herein included in the subfamily Triaenonychinae. Picunchenops Maury, 1988 originally not included in any tribe of Triaenonychidae, is herein included in the subfamily Triaenonychinae. Trojanella Karaman, 2005, originally ranked as Travunioidea incertae sedis, is herein included in the TravuniidaeTravuniinae. Nunciaovata Roewer, 1915 (synonymized with Triaenonyxcockayni Hogg, 1920 by Forster (1954), but with inverted precedence) is here combined as Nunciacoriaceaovata Roewer, 1915 as correct senior synonym instead of Nunciacoriaceacockayni (Hogg, 1920), which is current in the literature. Neonunciaenderbei (Hogg, 1909) is reaffirmed as the correct spelling for the species, while the deliberate change to Neonunciaenderbyi by Forster (1954) is an incorrect subsequent spelling.


Evaluation of candidate reference genes for quantitative expression studies in Asian seabass (Lates calcarifer) during ontogenesis and in tissues of healthy and infected fishes.
Quantitative real-time PCR (qRT-PCR), used to determine the gene expression profile, is an important tool in functional genomic research, including fishes. To obtain more robust and meaningful result, the best possible normalization of the data is of utmost significance. In the present study, we have evaluated the potential of five commonly used housekeeping genes i.e., elongation factor 1-α (EF1A), β-Actin (ACTB), 18S ribosomal RNA (18S), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-2-Microglobulin (B2M) in normal physiological conditions, developmental stages and in response to bacterial infection in Asian seabass, Lates calcarifer (Bloch), an important food fish cultured in the Asia-Pacific region. The expression levels of these five genes were estimated in 11 tissues of normal seabass juveniles, 14 embryonic and larval developmental stages and six tissues of Vibrio alginolyticus-challenged animals. Further, the expression stability of these genes was calculated based on three algorithms i.e. geNorm, NormFinder and BestKeeper. The results showed that although there are tissue-specific variations for each gene, ACTB and EF1A are the most stable genes across the tissues of normal animals. However, in bacteria-challenged animals, EF1A and 18S were found to be the best reference genes for data normalization. The expression of all the genes tested showed an increasing trend in developmental stages and the increase was significant at blastula stage. Among the five genes tested, EF1A and ACTB were found to be the genes with least variation and highest stability across the developmental stages. This forms the first report on validation of housekeeping genes in L. calcarifer, in the context of ontogenic development and in response to infection.


[The role of melatonin receptor and GABAA receptor in the sleeping time prolonged by melatonin in mice].
To observe the role of melatonin receptor and GABAA receptor in sleeping time prolonged by melatonin in mice. The absence of the righting reflex was considered as the sleep onset and the duration of the loss of the righting reflex was recorded as the sleeping time. The effects of receptor agonist and antagonist on hypnotic activity of melatonin were studied in the paper. Prazosin hydrochloride, the blocker of melatonin 3 receptor, didn't affect the sleeping time prolonged by melatonin in mice. GABA, the endogenous agonist of GABA receptor, significantly potentiated the hypnotic activity of melatonin. When picrotoxin, the ligand of picrotoxin site on GABAA receptor, used together with melatonin, it significantly antagonized the sleeping time prolonged by melatonin, however, bicuculline, the specific antagonist of GABA binding site in GABAA receptor, didn't affect the hypnotic activity of melatonin in mice. Melatonin does not exhibit its potentiation sleeping time in mice through melatonin 3 receptor. Hypnotic activity of melatonin may be mediated through picrotoxin site on GABAA receptor.


Evaluation of trueness and precision of two intraoral scanners and a conventional impression: an in vivo clinical study.
To evaluate, in vivo, trueness and precision of two intraoral scanners, CEREC Omnicam (OMNI) and CEREC Primescan (PRIM), compared to a conventional impression serving as a master model. Impressions were performed for seven participants. For each participant, conventional polyvinylsiloxane impression and digital impressions using two intraoral scanners, OMNI (software 4.6; CEREC ORTHO Protocol) and PRIM (10 digital impressions per participant, per scanner), were made. Conventional impression was digitized with a laboratory scanner (INEOS X5), and used as reference model. .STL files were superimposed with software (Geomagic Control X) using the tools Initial Alignment and Best Fit Alignment, and trueness and precision were evaluated. Statistical evaluation was performed with Shapiro-Wilk and Mann-Whitney tests (P < .05). Total mean trueness for the OMNI system was 56.45 ± 7.80 µm, and 47.29 ± 5.47 µm for the PRIM system. Regarding precision, values from the OMNI system were 42.47 ± 6.91 µm and from the PRIM system 21.86 ± 4.40 µm. PRIM presented better results for both trueness (P = .000) and precision (P = .000) when compared to OMNI. PRIM provided a better combination of trueness and precision than its predecessor OMNI. However, both PRIM and OMNI performed acceptably when performing indirect restorations, according to the current acceptable thresholds, considering both trueness and precision. Full-arch impressions with Primescan presented more precision and trueness than Omnicam; however, compared to previous reported values of conventional impressions, they still presented lower accuracy.


SPECIFICATIONS OF INTRACRANIAL SACCULAR ANEURYSMS, TREATED BY ENDOVASCULAR APPROACH USING DETACHABLE COILS.
The treatment of intracranial saccular aneurysms remains an actual problem due to this pathology prevalence among the human population (about 1-10%). For definition of efficiency and preventive importance of endovascular treatment, it is necessary to clear define which aneurysms are more suitable and operable for endovascular occlusion with minimal risk of complications and better final outcome. The aim of this study is to analyze anatomical features (location and structure) of intracranial saccular aneurysms and clinical data of patients who have been operated endovascular, with detachable coils in High Technology Medical Center University Clinic,Tbilisi, Georgia for the last 6 years. The study included 412 patients with 470 aneurysms who were operated from 2011 to 2016 using detachable coils. The age of patients ranged from 8 to 78 years. The largest number of patients belonged to the age group - 32-55 years. The men were 196 (47.6%), women - 216 (52.4%). In acute period 280 (68%) patients were operated, in the delayded period - 90 (21.8%), unruptured aneurysms - 42 (10.2%). Early results and outcomes (1-3 week) after endovascular treatment of SA were estimated with GOS. Full Recovery or Low disability was achieved in 313(76%) patient- GOS 5, Moderate disability in 48(11.7) patient- GOS 4 , Severe disability or Persistent vegetative state in 44(10.6%) patient- GOS 3-2 and GOS 1-death in 7(1.7%) patient. According to the study it can be concluded that endovascular treatment is a reliable, low-impact and effective way to treat the Saccular brain aneurysm. Despite the variety of aneurysm these treatments are optimistic and affirm the importance of endovascular treatment of cerebral aneurysms.


Medicinal Chemistry Insights into the Development of Small-Molecule Kelch-Like ECH-Associated Protein 1-Nuclear Factor Erythroid 2-Related Factor 2 (Keap1-Nrf2) Protein-Protein Interaction Inhibitors.
Oxidative stress has been implicated in a wide range of pathological conditions. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) exerts a central role in regulating the cellular defense system against oxidative and electrophilic insults. Nonelectrophilic inhibition of the protein-protein interaction (PPI) between Kelch-like ECH-associated protein 1 (Keap1) and Nrf2 has become a promising approach to activate Nrf2. Recently, multiple drug discovery strategies have facilitated the development of small-molecule Keap1-Nrf2 PPI inhibitors with potent activity and favorable drug-like properties. In this Perspective, we summarize the latest progress of small-molecule Keap1-Nrf2 PPI inhibitors from medicinal chemistry insights and discuss future prospects and challenges in this field.


Monitoring electron transfer by photoacoustic spectroscopy in native and immobilized thylakoid membranes.
Photoacoustic spectroscopy was used to monitor photo synthetic electron transfer in native and immobilized thylakoid membranes. The photoacoustic parameter phi(r)' (the percentage of absorbed energy that is stored in photo chemical intermediates) and i(50) (the half-saturation modulated light intensity) were directly correlated to electron transfer rates. As previously shown, thylakoids immobilized in an albumin-glutaraldehyde matrix were more resistant to aging. The inhibitory effects of the immobilization procedure and of aging at 4 degrees C were detected as a decrease in i(50) values. In analogy with enzyme kinetic analysis, the effect could be characterized as a competitive type of inhibition. Photoacoustic measurements are performed in conditions similar to a working bioreactor cell with regards to the sample preparation.


Cost-Effectiveness of Including a Nurse Specialist in the Treatment of Urinary Incontinence in Primary Care in the Netherlands.
Incontinence is an important health problem. Effectively treating incontinence could lead to important health gains in patients and caregivers. Management of incontinence is currently suboptimal, especially in elderly patients. To optimise the provision of incontinence care a global optimum continence service specification (OCSS) was developed. The current study evaluates the costs and effects of implementing this OCSS for community-dwelling patients older than 65 years with four or more chronic diseases in the Netherlands. A decision analytic model was developed comparing the current care pathway for urinary incontinence in the Netherlands with the pathway as described in the OCSS. The new care strategy was operationalised as the appointment of a continence nurse specialist (NS) located with the general practitioner (GP). This was assumed to increase case detection and to include initial assessment and treatment by the NS. The analysis used a societal perspective, including medical costs, containment products (out-of-pocket and paid by insurer), home care, informal care, and implementation costs. With the new care strategy a QALY gain of 0.005 per patient is achieved while saving €402 per patient over a 3 year period from a societal perspective. In interpreting these findings it is important to realise that many patients are undetected, even in the new care situation (36%), or receive care for containment only. In both of these groups no health gains were achieved. Implementing the OCSS in the Netherlands by locating a NS in the GP practice is likely to reduce incontinence, improve quality of life, and reduce costs. Furthermore, the study also highlighted that various areas of the continence care process lack data, which would be valuable to collect through the introduction of the NS in a study setting.


Isolation of an Escherichia coli mutant which permits the high-level expression of a streptomycin-resistance gene derived from Pseudomonas aeruginosa.
Pretreatment with streptomycin at a low concentration influenced the susceptibility to streptomycin of a strain of Escherichia coli carrying a streptomycin-resistance plasmid, pSA1700, derived from Pseudomonas aeruginosa. This phenomenon was due to a mutation that occurred at about 10(-8)-10(-10) of frequency in a regulatory gene involved in gene expression on the chromosome of E. coli. A product encoded by the regulatory gene on the chromosome of E. coli might normally repress gene expression by binding to part of the promoter region of the streptomycin-resistance gene derived from P. aeruginosa.


Data-Driven Packet Loss Estimation for Node Healthy Sensing in Decentralized Cluster.
Decentralized clustering of modern information technology is widely adopted in various fields these years. One of the main reason is the features of high availability and the failure-tolerance which can prevent the entire system form broking down by a failure of a single point. Recently, toolkits such as Akka are used by the public commonly to easily build such kind of cluster. However, clusters of such kind that use Gossip as their membership managing protocol and use link failure detecting mechanism to detect link failures cannot deal with the scenario that a node stochastically drops packets and corrupts the member status of the cluster. In this paper, we formulate the problem to be evaluating the link quality and finding a max clique (NP-Complete) in the connectivity graph. We then proposed an algorithm that consists of two models driven by data from application layer to respectively solving these two problems. Through simulations with statistical data and a real-world product, we demonstrate that our algorithm has a good performance.


Nonsense codons suppression. An acute toxicity study of three optimized TRIDs in murine model, safety and tolerability evaluation.
Stop mutations cause 11% of the genetic diseases, due to the introduction of a premature termination codon (PTC) in the mRNA, followed by the production of a truncated protein. A promising therapeutic approach is the suppression therapy by Translational Readthrough Inducing Drugs (TRIDs), restoring the expression of the protein. Recently, three new TRIDs (NV848, NV914, NV930) have been proposed, and validated by several in vitro assays, for the rescue of the CFTR protein, involved in Cystic Fibrosis disease. In this work, an acute toxicological study for the three TRIDs was conducted in vivo on mice, according to the OECD No.420 guidelines. Animals were divided into groups and treated with a single dose of TRIDs molecules or Ataluren, an FDA-approved TRID molecule, as control. Mice were observed continuously for the first day post-drugs administration and the behavioral changes were recorded. On the 15th day, animals were sacrificed for histological examinations. The results showed that acute administration of 2000 mg/kg of NV914 and Ataluren and 300 mg/kg of NV848 or NV930, did not induce any mortality within 14 days. Moreover, histopathological analysis of treated mice showed no differences when compared to the experimental controls. In summary, our results suggest a good tolerability for the three molecules, and include NV848 and NV930 in a category 4 and NV914 in a category 5 of the Globally Harmonized System (GHS) of Classification and Labeling of Chemicals, classifying these compounds in a low-risk scale for health.


Serotonin receptors and cognitive behaviour--an update.
The serotonergic system appears to play a role in behaviors that involve a high cognitive demand and in memory improvement or recovery from an impaired cognitive performance. This is made evident after administration of 5-HT(2A/2C), and 5-HT4 receptor agonists, or 5-HT1A, 5-HT3 and probably 5-HT1B receptor antagonists. These serotonin receptor subtypes are localized on 'cognitive' pathways, with the hippocampus and frontal cortex as the main target structures. A better understanding of the role played in cognition by these and other serotonin receptor subtypes is likely to result from the recent availability of highly specific ligands such as 5-HT1A, 5-HT1B, and 5-HT2A receptor antagonists, and new molecular tools such as gene knock-out mice, especially inducible mice for which the genetic alteration can be restricted both temporally and anatomically.


Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with Advanced Solid Tumors.
The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS <10), for whom ST is deemed appropriate for toxicity. The primary objective was to estimate the agreement in chemotherapy choice (ST vs. RT) between the treating physician and the CTRS using a κ statistic. Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS <10, and 17 had CTRS ≥10), and 20 patients received RT (12 had CTRS ≥10, and 8 had CTRS <10), with minimal agreement in chemotherapy choice (κ = 0.14; 95% CI, -0.10 to 0.38). Grade 3-4 toxicity and hospitalization occurred in 60% and 27% of 55 patients with follow-up data, respectively. Among patients receiving ST, patients with CTRS ≥10 had a higher incidence of toxicity (88% vs. 40%, p = .006) and hospitalization (50% vs. 15%, p = .03) than those with CTRS <10. Older patients with cancer with a high CTRS who receive combination chemotherapy have an exceedingly high rate of severe toxicity and hospitalization. The potential utility of the chemotherapy toxicity risk score (CTRS) in old adults with advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3-4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (<10). These findings suggest that the addition of CTRS to the clinical impression has a potential to improve treatment decisions.


Correction of Cleft Lip Nose Deformity With Circular Shape Alar Graft and Block Costal Cartilage.
Secondary deformities of the cleft lip and nose are mainly caused by the long period of craniofacial development and the secondary scarring. Correction of the secondary cleft lip-nose deformity is a complex process that requires both the correction of the soft tissue and skeletal support. The purpose of this study was to present our experience in correcting the secondary unilateral cleft lip-nose deformities with autologous costal cartilage. A retrospective analysis of patients who underwent correction of unilateral cleft nasal deformity with simultaneous rhinoplasty by a senior surgeon from January 2015 to January 2022 was conducted. Preoperative and postoperative measurements of the columellar-labial angle and the inclination of nasal base were conducted to evaluate the surgical outcomes. A total of 54 patients were included in this study according to the inclusion criteria. The mean follow-up period was 4 years (range, 1-7 years). The mean values of the columellar-labial angle were 91.1 ± 9.2 degrees preoperatively and 101.0 ± 5.9 degrees postoperatively. The mean values of the inclination of nasal base were 4.5 ± 1.2 degrees preoperatively and 0.9 ± 0.4 degrees postoperatively. There was a considerable increase in the columellar-labial angle after the surgery (9.9 ± 6.0 degrees; P < 0.01). The inclination of nasal base decreased significantly (3.6 ± 1.1 degrees; P < 0.01). Our approach on correction the secondary clef lip nose through repositioning the muscles by Z-plasty and application of the block cartilage graft and circular shape alar graft has achieved long-term satisfactory results.


Metabolic effects of using a variable impedance prosthetic knee.
A transfemoral amputation has a significant effect on walking. Though current prosthetic knee options serve to restore mobility, as do purely passive devices, they do not fully restore nondisabled gait. Persons with transfemoral amputation incur a higher metabolic cost during walking than persons without amputation and as a result walk slower and for a shorter distance before tiring. An original variable-impedance transmission prosthetic knee (VI Knee) was tested with five study participants with unilateral transfemoral amputation at two steady-state walking speeds, one below and one above their preferred walking speed. While walking with the VI Knee, participants with shorter limbs showed a reduction in metabolic cost compared with their conventional C-Leg prosthesis, while those with longer limbs exhibited an increase. Though differences were observed between speeds, overall, the difference in metabolic cost (reduction or increase) was found to correlate significantly with rise in the center of mass, with those with shorter residual limbs exhibiting less overall lifting of the body during gait.


Structural basis for the efficient phosphorylation of AZT-MP (3'-azido-3'-deoxythymidine monophosphate) and dGMP by Plasmodium falciparum type I thymidylate kinase.
Plasmodium falciparum is the causative agent of malaria, a disease where new drug targets are required due to increasing resistance to current anti-malarials. TMPK (thymidylate kinase) is a good candidate as it is essential for the synthesis of dTTP, a critical precursor of DNA and has been much studied due to its role in prodrug activation and as a drug target. Type I TMPKs, such as the human enzyme, phosphorylate the substrate AZT (3'-azido-3'-deoxythymidine)-MP (monophosphate) inefficiently compared with type II TMPKs (e.g. Escherichia coli TMPK). In the present paper we report that eukaryotic PfTMPK (P. falciparum TMPK) presents sequence features of a type I enzyme yet the kinetic parameters for AZT-MP phosphorylation are similar to those of the highly efficient E. coli enzyme. Structural information shows that this is explained by a different juxtaposition of the P-loop and the azide of AZT-MP. Subsequent formation of the transition state requires no further movement of the PfTMPK P-loop, with no steric conflicts for the azide moiety, allowing efficient phosphate transfer. Likewise, we present results that confirm the ability of the enzyme to uniquely accept dGMP as a substrate and shed light on the basis for its wider substrate specificity. Information resulting from two ternary complexes (dTMP-ADP and AZT-MP-ADP) and a binary complex with the transition state analogue AP5dT [P1-(5'-adenosyl)-P5-(5'-thymidyl) pentaphosphate] all reveal significant differences with the human enzyme, notably in the lid region and in the P-loop which may be exploited in the rational design of Plasmodium-specific TMPK inhibitors with therapeutic potential.


Dysphoria among high-risk pregnant hospitalized women on bed rest: a longitudinal study.
While approximately 700,000 women experience pregnancy complications and are treated with bed rest in the hospital each year, little is known about negative affect in these women. The study purpose was to describe dysphoria, a composite of symptoms of negative affect across the antepartum and postpartum and to identify the relationship between dysphoria and the length of pre-admission home bed rest, hospital bed rest, and maternal and fetal/neonatal indices of risk. The convenience sample for this longitudinal repeated measures study consisted of 63 high-risk pregnant women admitted on antepartum bed rest to one of three university-affiliated hospitals. Women were included if they were diagnosed with (a) preterm labor, (b) premature rupture of membranes, (c) incompetent cervix, (d) placenta previa, (e) placental abruption or multiple gestation, and (f) did not have a psychiatric disorder. The Multiple Affect Adjective Checklist-Revised (MAACL-R) was used to assess dysphoria. Obstetric risk status was assessed by both the Hobel and Creasy Risk Assessment tools. Dysphoria was highest upon hospital admission and decreased significantly across time (F (5) = 23.58, p <.001). Positive Affect-Sensation Seeking significantly increased across time (F (5) = 53.16, p <.001). Dysphoria scores were significantly greater for those with highest Hobel obstetric risk scores (F (1, 60) = 4.53, p =.037). Antepartum dysphoria was not correlated with gestational age upon hospital admission, length of bed rest, or Creasy risk status. However, gestational age at birth was significantly correlated with postpartum dysphoria. The stimulus for antepartum dysphoria is unclear. However, postpartum dysphoria appears to be related to indicators of the infant's state of health at birth.


FRL: An Integrative Feature Selection Algorithm Based on the Fisher Score, Recursive Feature Elimination, and Logistic Regression to Identify Potential Genomic Biomarkers.
Accurate screening on cancer biomarkers contributes to health assessment, drug screening, and targeted therapy for precision medicine. The rapid development of high-throughput sequencing technology has identified abundant genomic biomarkers, but most of them are limited to single-cancer analysis. Based on the combination of Fisher score, Recursive feature elimination, and Logistic regression (FRL), this paper proposes an integrative feature selection algorithm named FRL to explore potential cancer genomic biomarkers on cancer subsets. Fisher score is initially used to calculate the weights of genes to rapidly reduce the dimension. Recursive feature elimination and Logistic regression are then jointly employed to extract the optimal subset. Compared to the current differential expression analysis tool GEO2R based on the Limma algorithm, FRL has greater classification precision than Limma. Compared with five traditional feature selection algorithms, FRL exhibits excellent performance on accuracy (ACC) and F1-score and greatly improves computational efficiency. On high-noise datasets such as esophageal cancer, the ACC of FRL is 30% superior to the average ACC achieved with other traditional algorithms. As biomarkers found in multiple studies are more reliable and reproducible, and reveal stronger association on potential clinical value than single analysis, through literature review and spatial analyses of gene functional enrichment and functional pathways, we conduct cluster analysis on 10 diverse cancers with high mortality and form a potential biomarker module comprising 19 genes. All genes in this module can serve as potential biomarkers to provide more information on the overall oncogenesis mechanism for the detection of diverse early cancers and assist in targeted anticancer therapies for further developments in precision medicine.


Variable ratio blue/red upconversion in Yb3+-Tm3+ codoped fluorosilicate glasses.
Simultaneous blue-red emission in a fiber pumped by a single wavelength source is perceived as a great challenge because of the large energy difference of the emitted photons. This Letter reports the dependence of the blue-to-red upconversion (UC) emission ratio in Yb3+-Tm3+ codoped fluorosilicate glasses (FSGs) under the excitation of a 980-nm laser on the host glass silica content. Photoluminescence spectra and SEM-EDS are used to clarify the UC mechanism, indicating that the probability of the cross-relaxation (CR) process 1G4 + 3F2→3H6 + 3F4 is key to the dominance of the blue or red emissions. This research can provide a new platform for variable UC luminescence.


Favorable effect of creams with skimmed donkey milk encapsulated in nanoliposomes on skin physiology.
The use of donkey milk has a long history in external dermal application for cosmetic and medical purposes. The encapsulation of different drugs into nanoliposomes and nutrients may have many benefits for the delivery of the targeted substance. The aim of the present study is to test creams with nanoliposomes encapsulated with skimmed donkey milk, reported in our registered patent, compared with effect of the placebo cream and the untreated skin. To investigate the effect of formulated cream, we have measured the electrical capacitance, transepidermal water loss and the skin pH value. The study included 15 healthy volunteers (11 women and 4 men). The patented creams exhibited satisfactory moisturizing properties very soon after application, while hydration was reached earlier in the spots treated with night cream. Transepidermal water loss slightly decreased only after 4 weeks of treatment in each of the spots assessed. The pH value was similar after each of the treatments. Tested creams may enhance the moisture of skin very soon after application, in this way potentially enable deeper permeation of phospholipids and essential proteins, without changing the pH. It may also contribute to additional anti-aging effects.


Spatio-temporal evolution on geographic boundaries of HFRS endemic areas in Shandong Province, China.
To take effective strategies and measures for the prevention and control of hemorrhagic fever with renal syndrome (HFRS) endemic areas by investigating its dynamic geographical boundaries in Shandong Province, China. The incidence of HFRS from 1982 to 2008 in Shandong Prvince, China, was detected with inverse distance weighting (IDW) interpolation based on geographical information system (GIS). Dynamic geographical boundaries of HFRS endemic areas in Shandong Province, China, were analyzed by geographical boundary analysis. The HTN-type endemic areas of HFRS were located in Linyi City in phase 1 (1982-1986), the SEO-type endemic areas of HFRS were located in Jining City in phase 2 (1987-2003), and the endemic areas of HFRS in Jining City gradually disappeared and the endemic areas of HFRS with mixed-types of reservoir rodents were located in Linyi City in phase 3 (2004-2008). Meanwhile, new endemic areas emerged in the northwestern Shandong province, China. The SEO-type endemic areas of HFRS are located in western Shandong Province, China, and the HTN-type endemic areas of HFRS are located eastern Shandong Province, Chin, indicating that the endemic areas of HFRS should be vaccinated and rodents should be controlled.


Disynaptic amplification of metabotropic glutamate receptor 1 responses in the olfactory bulb.
Sensory systems often respond to rapid stimuli with high frequency and fidelity, as perhaps best exemplified in the auditory system. Fast synaptic responses are fundamental requirements to achieve this task. The importance of speed is less clear in the olfactory system. Moreover, olfactory bulb output mitral cells respond to a single stimulation of the sensory afferents with unusually long EPSPs, lasting several seconds. We examined the temporal characteristics, developmental regulation, and the mechanism generating these responses in mouse olfactory bulb slices. The slow EPSP appeared at postnatal days 10-11 and was mediated by metabotropic glutamate receptor 1 (mGluR1) and NMDA receptors. mGluR1 contribution was unexpected because its activation usually requires strong, high-frequency stimulation of inputs. However, dendritic release of glutamate from the intraglomerular network caused spillover-mediated recurrent activation of metabotropic glutamate receptors. We suggest that persistent responses in mitral cells amplify the incoming sensory information and, along with asynchronous inputs, drive odor-evoked slow temporal activity in the bulb.


Findings From a Provider-Led, Mindfulness-Based, Internet-Streamed Yoga Video Addressing the Psychological Outcomes of Breast Cancer Survivors.
The aim of this study was to explore the psychological outcomes of a mindfulness-based Internet-streamed yoga video in breast cancer survivors. A one-group, repeated-measures, purposive sample using a directed qualitative descriptive and convergent mixed-methods approach was used. Participants were recruited from breast oncology practices across 2 settings in the northeastern United States in April 2019. Education about the video was provided, and the link to the video was sent to participants. Demographic information, Knowing Participation in Change Short Form (KPCSF), Short Warwick-Edinburgh Mental Well-being Scale (WEMWBS), and the Generalized Anxiety Distress Scale (GAD-7) were obtained at baseline and at 2 and 4 weeks. A semistructured interview was conducted at 4 weeks. Thirty-five women (mean age = 56 years) participated. A one-group, repeated-measures analysis of variance indicated statistically significant changes occurred in all measures between week 0 and week 4: decreased GAD (t = -2.97, P = .004), improved WEMWBS (t = 2.52, P = .008), and increased KPC (t = 2.99, P = .004). Qualitative findings suggest the overall experience of the video was positive and the women would recommend its use to others. Improvements in all psychological measures were achieved with video use. Findings indicate an improvement in psychological measures and support the theory of Knowing Participation in Change. This work further contributes to accessible, flexible interventions available through the Internet and/or mobile applications aimed at improving breast cancer survivorship.


IP3 receptor-mediated Ca2+ release in naive CD4 T cells dictates their cytokine program.
IP(3) (inositol 1,4,5-trisphosphate) receptors (IP(3)Rs) regulate the release of Ca(2+) from intracellular stores in response to IP(3). Little is known about regulation of the expression of IP(3)Rs and their role during the activation of CD4 T cells. In this study we show that mouse naive CD4 T cells express IP(3)R1, IP(3)R2, and IP(3)R3, but that gene expression of IP(3)R3 primarily is down-regulated upon activation due to loss of the Ets-1 transcription factor. Down-regulation of IP(3)R expression in activated CD4 T cells is associated with the failure of TCR ligation to trigger Ca(2+) release in these cells. We also show that down-regulation of specific IP(3)Rs in activated CD4 T cells correlates with the requirement of IP(3)R-mediated Ca(2+) release only for the induction of, but not for the maintenance of, IL-2 and IFN-gamma expression. Interestingly, while inhibition of IP(3)R function early during activation blocks IL-2 and IFN-gamma production, it promotes the production of IL-17 by CD4 T cells. Thus, IP(3)Rs play a key role in the activation and differentiation of CD4 T cells. The immunosuppressive effect of pharmacological blockers of these receptors may be complicated by promoting the development of inflammatory CD4 T cells.