HIV prevention programmes for female sex workers in Andhra Pradesh, India: outputs, cost and efficiency.
Female sex workers and their clients play a prominent role in the HIV epidemic in India. Systematic data on the outputs, cost and efficiency for HIV prevention programmes for female sex workers in India are not readily available to understand programme functioning and guide efficient use of resources. Detailed output and cost data for the 2002-2003 fiscal year were obtained using standardised methods at 15 HIV prevention programmes for female sex worker in the state of Andhra Pradesh in southern India. The services provided and their relation to the total and unit economic costs were analysed using regression techniques. The trends for the number of sex workers provided services by the programmes since inception up to fiscal year 2004-2005 were examined. The 15 programmes provided services to 33941 sex workers in fiscal year 2002-2003 (range 803-6379, median 1970). Of the total number of contacts with sex workers, 41.6% were by peer educators and 58.4% by other programme staff. The number of sex worker contacts in a year by peer educators varied 74-fold across programmes as compared with a 2.7-fold variation in sex worker contacts by other programme staff. The annual economic cost of providing services to a sex worker varied 6-fold between programmes from Indian Rupees (INR) 221.8 (4.58 US dollars) to INR 1369 (28.29 US dollars) with a median of INR 660.9 (13.66 US dollars) and mean of INR 517.8 (10.70 US dollars). Personnel salaries made up 34.7% of the total cost, and recurrent goods made up 38.4% of which 82.1% was for condoms. The cost per sex worker provided services had a significant inverse relation with the number of sex workers provided services by a programme (p < 0.001, R2 = 0.75; power function). There was no correlation between the full time equivalents of programme staff and the number of sex workers provided services by the programmes, but there was a modest inverse correlation between the number of sex workers served and the average time spent with each sex worker in the year adjusted for the full-time equivalents of programme staff (p = 0.011, R2 = 0.40; exponential function). The average number of sex workers provided services annually by the first batch of 7 programmes started in early 1999 plateaued after the fourth fiscal year to 3500, whereas the 8 second-batch programmes started in late 2000 reached an average of 2000 sex workers in 2004-2005 with an increasing trend up to this fourth fiscal year. The HIV prevention efforts in this Indian state would benefit from standardisation of the highly variable services provided by peer educators, who form an important part of the sex worker programmes. The cost per sex worker served decreases with increasing number of sex workers served annually, but this has to be weighed against an associated modest trend of decrease in time spent with each sex worker in some programmes.


The effect of subinhibitory concentrations of antibiotics on adherence of Pseudomonas aeruginosa to cystic fibrosis (CF) and non-CF-affected tracheal epithelial cells.
this project investigated the proposition that Pseudomonas aeruginosa binds preferentially to cystic fibrosis (CF) respiratory cells. In addition, disadherence of P. aeruginosa by subinhibitory concentrations of antibiotics was examined as a possible explanation for clinical improvement seen in chronically colonized patients when treated with anti-pseudomonal agents. we used a distinctive HPV-transformed respiratory cell line to compare adherence of two strains of P. aeruginosa to CF and non-CF respiratory cells. The effect of subinhibitory concentrations of antipseudomonal antibiotics on adherence of P. aeruginosa to cell monolayers was measured. piliated P. aeruginosa bound significantly better to CF than non-CF-affected cells (P=0.003). Adherence was significantly reduced when organisms were preincubated in subinhibitory concentrations of antibiotics overnight (P<0.001). these results support the presence of an altered receptor present on CF-affected cells that binds piliated strains of P. aeruginosa. Bacterial disadherence due to subinhibitory concentrations of antibiotics may partially explain why clinical improvement is observed in CF patients with acute respiratory exacerbations.


Changes in lymphocyte beta-adrenergic receptors in depression and mania.
The beta-adrenergic receptors were studied in vitro in lymphocytes obtained from patients with major affective disorders and controls. Specific L-[3H]-dihydroalprenolol binding was decreased in both depressed and manic patients compared to controls and euthymic patients. Isoproterenol-stimulated, but not prostaglandin El-stimulated, cyclic adenosine-3',5'-monophosphate production was decreased in manic and depressed patients. These results suggest decreased lymphocyte beta-receptor functioning in depression and mania. This decrease may be an index of changes in brain beta-receptors in mania and depression, or may simply reflect homeostatic regulation of peripheral beta-receptors in response to stress-induced increases in circulating catecholamines.


Lumbar puncture safety and tolerability in premanifest and manifest Huntington's disease: a multi-analysis cross-sectional study.
Lumbar puncture (LP) has become increasingly common for people with Huntington's disease (HD) both to administer intrathecal investigational medicinal products and to collect cerebrospinal fluid to develop biological markers to track disease stage and progression. We aimed to investigate the safety profile of LP in people with HD, building on a recently published work by increasing the sample size and more specifically, increasing the representation of the premanifest population and healthy controls. We conducted a multi-study cross-sectional analysis including eligible participants from the HDClarity (304 Huntington's disease gene expansion carriers and 91 controls) and HD-YAS studies (54 premanifest and 48 controls), enrolled between February 2016 and September 2019. We investigated the odds of any adverse events, headaches, and back pain independently. Intergroup comparisons and adjusted event odds were derived using hierarchical logistic regressions. A total of 669 LP procedures involving 497 participants were included in this analysis. There were 184 (27.5%) LP procedures associated with one or more adverse events. The two most common adverse events were: post LP headache and back pain. Younger age and female gender were found to be associated with a higher risk of developing adverse events. There was no difference in the rate of adverse events between the disease subgroups after adjusting for covariates such as age and gender. Our results suggest that the LP is safe and tolerable in premanifest and manifest HD subjects, providing useful reassurance about the procedure to the HD community.


Aerobic exercise regulates GPR81 signal pathway and mediates complement- microglia axis homeostasis on synaptic protection in the early stage of Alzheimer's disease.
Memory impairment is a major clinical manifestation in Alzheimer's disease (AD) patients, while regular exercise may prevent and delay degenerative changes in memory functions, and our aim is to explore the influence and molecular mechanisms of aerobic exercise on the early stages of Alzheimer's disease. 3-month-old male APP/PS1 transgenic AD mice and C57BL/6J wild-type mice were randomly divided into four groups: wild-type and APP/PS1 mice with sedentary (WT-SED, AD-SED), and running (WT-RUN, AD-RUN) for 12-weeks. The spatial learning and memory function, RNA-sequencing, spine density, synaptic associated protein, mRNA and protein expression involved in G protein-coupled receptor 81 (GPR81) signaling pathway, and complement factors in brain were measured. Aerobic exercise improved spatial learning and memory in APP/PS1 mice, potentially attributed to increased dendritic spine density. Subsequently, potential underlying mechanisms were identified through RNA sequencing: regular aerobic exercise could activate the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) cAMP/PKA signaling pathway and upregulate synaptic function-related proteins to promote synaptic growth, possibly by modulating GPR81. Notably, regular aerobic exercise inhibited microglial activation, reversed the microglial phenotype, reduced the production of initiation factor C1q and central factor C3 in the complement cascade in the brain, prevented the colocalization of microglia and PSD-95, and thus prevented synaptic loss. Physical exercise could play a critical role in improving cognitive function in AD by promoting synaptic growth and preventing synaptic loss, which may be related to the regulation of the GPR81/cAMP/PKA signaling pathway and inhibition of complement-mediated microglial phagocytosis of synapses.


Synthesis of new steroid haptens for radioimmunossay. Part IV. 3-O-Carboxymethyl ether derivatives of estrogens. Specific antisera for radioimmunossay of estrone, estradiol-17beta, and estriol.
The syntheses of 3-O-carboxymethyl ether derivatives of estrone, estradiol-17beta, and estriol and the preparation of their bovine serum albumin (BSA) conjugates are described. These conjugates were employed for the generation of specific antisera suitable for radioimmunoassay (RIA) of estrone, estradiol-17beta, and estriol. The previous concept that specific antisera for estrogens cannot be obtained by employing estrogens derivatized at the 3-position is unfounded.


Inadvertent Dural Puncture during Caudal Approach by the Introducer Needle for Epidural Adhesiolysis Caused by Anatomical Variation.
There have been reports of abnormalities in the lumbosacral region involving a lower-than-normal termination of the dural sac, which is caused by disease or anatomical variation. Inadvertent dural puncture or other unexpected complications can occur during caudal epidural block or adhesiolysis in patients with these variations, but only a small number of case reports have described this issue. We report a case of dural puncture by the introducer needle before attempting caudal epidural adhesiolysis, which occurred even though the needle was not advanced upward after penetrating the sacrococcygeal ligament. Dural puncture was caused by a morphological abnormality in the lumbosacral region, with no pathological condition; the dural sac terminal was located more distally than normal. However, dural puncture could have been prevented if we had checked for such an abnormality in the magnetic resonance imaging (MRI) taken before the procedure.


Assays for Inducing and Measuring Cell Death to Detect Macrophage Migration Inhibitory Factor (MIF) Release.
Cell death is a vital process for maintaining tissue homeostasis and removing potentially harmful cells. Cell death can be both programmed and non-programmed and is commonly divided into two main forms, termed apoptotic and necrotic death modes. In this chapter cell death is classified into apoptosis, primary necrosis, pyroptosis, and necroptosis. This chapter outlines the measurement of these different types of cell death and the relationship of measuring MIF release in these assays.


Stakeholder views of services for children and adolescents with obesity: Mega-ethnography of qualitative syntheses.
The efficacy of services for children and adolescents with obesity is well researched, but this review describes what actually matters to stakeholders (children, caregivers, and professionals) in relation to such services. A mega-ethnography, an innovative review-of-reviews approach that uses conceptual findings as primary data, was performed. Twelve bibliographic databases (2010-2020) were searched for reviews that considered the values and preferences of stakeholders concerning services or interventions (diet, exercise, lifestyle) that targeted children and adolescents with obesity. From 485 citations, 17 relevant reviews were identified. The synthesis found that the perceived need to address obesity is determined by subjective norms of weight and interactions with health professionals. Children's and caregivers' participation in obesity management services is shaped by their response to content, acceptability, and perceived benefits and demands. Whether they continue with and complete an intervention are determined by its perceived success, beyond just weight loss, including behavior change, enhanced self-esteem, and the provision of timely and relevant support. Obesity management services must be promoted in a sensitive manner and must be tailored, be varied, and make positive use of family and schools if children and caregivers are to seek and actively engage with them.


Transpalpebral midface lift.
Aging of the midface is a complex aesthetic problem requiring an individualized and multifaceted surgical approach. The objective of harmonious rejuvenation of the entire face as well as increasing patient interest in midface rejuvenation mandates surgical familiarity with these techniques. Midface rejuvenation procedures have evolved from traditional laterally based rhytidectomy techniques with superolateral elevation to modern centrofacial approaches designed to achieve more vertical vectors of elevation. These approaches are informed by an evolving understanding of the multiple processes that contribute to the aged appearance of the midface and are based on lower blepharoplasty surgical techniques.


Examining Longitudinal Stimulant Use and Treatment Attendance as Parallel Outcomes in Two Contingency Management Randomized Clinical Trials.
The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one 'parallel outcomes' model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β=0.060, p<0.05). In the second trial, CM predicted negative urinalysis ((-)UA) over the 12-week treatment period (β=0.069, p<0.05). In both trials, there was a significant, positive relationship between attendance and (-)UA submission, but in the first trial a (-)UA at both baseline and over time was related to attendance over time (r=0.117; r=0.013, respectively) and in the second trial, a (-)UA submission at baseline was associated with increased attendance over time (r=0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This 'indirect reinforcement' between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials.


Exploration of the pathogenesis of Sjögren's syndrome via DNA methylation and transcriptome analyses.
Sjögren's syndrome (SS), a systemic autoimmune disorder, is characterized by dry mouth and eyes. However, SS pathogenesis is poorly understood. We performed bioinformatics analysis to investigate the potential targets and molecular pathogenesis of SS. Gene expression profiles (GSE157159) and methylation data (GSE110007) associated with SS patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially methylated positions (DMPs) and differentially expressed genes (DEGs) were identified by the R package limma. The potential biological functions of DEGs were determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Key DMPs were selected by overlap and the shrunken centroid algorithm, and corresponding genes were identified as hub genes, with their diagnostic value assessed by receiver operating characteristic (ROC) curves. The potential molecular mechanisms of hub genes were analyzed by protein-protein interaction (PPI) networks and single-gene gene set enrichment analysis (GSEA). Peripheral blood mononuclear cells (PBMCs) were collected from control and SS patients at The Affiliated Hospital of Southwest Medical University and Dazhou Central Hospital. The mRNA levels of hub genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR). We identified 788 DMPs and 2457 DEGs between the two groups. Functional enrichment analysis suggested that the DEGs were significantly enriched in T cell activation, leukocyte cell-cell adhesion, and cytokine-cytokine receptor interaction. TSS200, TSS1500, and 1stExon were identified as highly enriched areas of differentially methylated promoter CpG islands (DMCIs). In total, 61 differentially methylated genes (DMGs) were identified by the overlap of 2457 DEGs and 507 genes related to DMPs (DMPGs), of which 21 genes located near TSS200, TSS1500, and 1stExon were selected. Then, three key DMPs and the corresponding hub genes (RUNX3, HLA-DPA1, and CD6) were screened by the shrunken centroid algorithm and calculated to have areas under the ROC curve of 1.000, 0.931, and 0.986, respectively, indicating good diagnostic value. The GSEA results suggested that all three hub genes were highly associated with the immune response. Finally, positive mRNA expression of the three hub genes in clinical SS samples was verified by qRT-PCR, consistent with the GSE157159 data. The identification of three hub genes provides novel insight into molecular mechanisms and therapeutic targets for SS. Key Points • Hub genes were screened by DNA methylation and transcriptome analyses. • The relative expression of hub genes in peripheral blood samples was verified by qRT-PCR. • HLA-DPA1 was correlated with the pathogenic mechanism of SS.


EQ-5D-5L Bulgarian population norms.
The present study aimed to provide normative data for the EQ-5D-5L questionnaire in Bulgaria, based on a nationally representative sample. Random sampling was used. In September 2018, a total of 1005 respondents (aged 18-89 years) completed the self-administered paper-based EQ-5D-5L questionnaire, including a visual analogue scale (EQ VAS). Health state utility index scores were derived using the directly measured Polish value set. The study sample was representative of the general Bulgarian population in terms of age, sex, geographical region, educational level, social and professional status. Mean EQ-5D-5L and EQ VAS values decreased from 0.986 and 89.7 (age group 18-24 years) to 0.789 and 53.6 (age group ≥ 75 years), respectively. Perfect health (the "11,111" health state) was reported by half of the population (50.1%), more often by men than women (55.8% vs 44.9%). The most frequently reported complaints characterised pain/discomfort dimension (39.1%), followed by anxiety/depression (34.5%). Although the least commonly reported health limitations concerned the self-care dimension, their frequency (13.6%) was the highest among the seventeen identified EQ-5D-5L population norm studies. The mean severity index score for the whole study sample was 6.96. EQ-5D-5L index was higher in respondents from lower age groups and with a higher average income per household member. Bulgarian population norms, which were developed for the descriptive part of the EQ-5D-5L and EQ VAS, can be used as reference values. The availability of such normative data should encourage the use of the EQ-5D-5L questionnaire in health-related quality-of-life studies in Bulgaria.


Pathways of lymph flow through superficial inguinal lymph nodes in the pig.
The pig lymph node has an unusual structure in that tissue containing lymph nodules generally occupies a central position. Our aim was to describe the lymphatic pathways through this node. We studied the structure of these pathways with light and electron microscopy, made casts of lymphatic vessels and sinuses with Microfil, and studied the distribution within the node of subcutaneously injected carbon particles. Most afferent lymphatics penetrate deeply within the node, where they give off several branches to peritrabecular sinuses that ramify through centrally located nodular tissue. However, where an afferent lymphatic enters the node there is a subcapsular sinus over an area of nodular tissue that occupies a conventional superficial position. Some lymph reaches this sinus from the central peritrabecular sinuses, but there can also be direct communications between this sinus and the afferent lymphatic. After flowing through sinuses in nodular tissue, lymph enters tissue that is analogous to medullary tissue in other species. This tissue is of two types, one consisting mainly of a diffuse network of reticular cells around spaces up to 10-12 microns across, and one that more closely resembles conventional medullary tissue. Lymph then flows to collecting ducts, which lack valves, and then to efferent lymphatics. Our findings do not support suggestions that a purely physical obstruction of lymphocytes in the lymph node accounts for the dearth of lymphocytes in efferent lymph of pigs.


Postoperative MR imaging features after superior semicircular canal plugging in Minor syndrome.
To report the postoperative magnetic resonance imaging (MRI) features after superior semicircular canal plugging in patients with Minor syndrome. The MRI examinations with 3D T2-weighted SPACE sequence of 12 patients with superior semicircular canal dehiscence syndrome (SCDS) were retrospectively assessed. Two radiologists independently evaluated the presence of a filling defect of the superior semicircular canal above the superior ampulla and the common crus using an oblique plane parallel to the superior semicircular canal (Pöschl's plane). Postoperative MRI showed a filling defect above the ampulla of the superior semicircular canal and the common crus in 8/12 patients (67%). Three patients (3/12; 25%) had a filling defect involving also the superior ampulla that caused postoperative labyrinthitis with labyrinthine enhancement on MRI in 2 patients. One patient (1/12; 8%) had incomplete plugging of superior semicircular canal with abnormal functional tests and remaining symptoms. Postoperative MRI shows a normal plugging aspect of the superior semicircular canal in 67% of patients. MRI can reveal complications that may have therapeutic implications.


Open acetabular fracture: Case report and literature review.
Acetabular fractures are a rare injury, with a reported annual incidence of 3 patients per 100,000 per year. Open fractures of the acetabulum are extremely rare, with only explosive penetrating trauma (blast or gunshot injury) being previously reported. An open acetabular fracture as a result of blunt trauma is presented, in which the only indication was a wound in the buttock, in which early definitive surgical management of the injury provided a good clinical outcome.


In vitro exposure of Penicillium mycotoxins with or without a modified yeast cell wall extract (mYCW) on bovine macrophages (BoMacs).
Penicillium mycotoxins (PMs) are contaminants that are frequently found in grain or crop-based silage for animal feed. Previously, we have characterized the potential immunotoxicity of the following PMs: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA), and penicillic acid (PA) by using a bovine macrophage cell line (BoMacs). In the present study, cell proliferation was used as a bioassay endpoint to evaluate the efficacy of a modified yeast cell wall extract (mYCW), for preventing PM toxicity under various in vitro conditions such as the following: pH (3, 5, 7), incubation time (1, 2, 4, 6 h), percentage of mYCW (0.05, 0.1, 0.2, 0.5, 1.0 %), and PM concentration. mYCW was most effective in preventing the toxicity of 12.88 and 25.8 μM OTA at pH 3.0 (p < 0.0001), regardless of incubation time (p < 0.0001) and the percentage of mYCW (p < 0.0001). An incubation time of 6 h (p < 0.05) or 0.5 and 1.0 % mYCW (p < 0.0001) significantly improved the efficacy of mYCW for preventing CIT toxicity. In contrast, 0.5 and 1.0 % of mYCW appeared to exacerbate the PAT toxicity (p < 0. 0001). This effect on PAT toxicity was constantly observed with higher PAT concentrations, and it reached significance at a concentration of 0.70 μM (p < 0.0001). mYCW had no effect on PA toxicity. These results suggest that mYCW may reduce OTA toxicity and, to some extent, CIT toxicity at pH 3.0. Although PAT toxicity was increased by mYCW treatment, PAT is readily degraded during heat treatment and may therefore be dealt with using other preventative measures.


[Comparative histoenzymological demonstration of certain digestive enzymes in the intestinal epithelium of the mouse and the chicken during a 24-h-period (author's transl)].
At different times of the day activities of hydrolytic (alkaline and acid phosphatase, esterase) and oxydative (succinodehydrogenase, cytochromoxidase, monoaminoxidase) enzymes were studied in the epithelium of the upper part of the jejunum in the adult female mouse and the adult laying chicken. In both species the activities of the intestinal enzymes showed marked circadian variations with respect to their activity and distribution pattern. The variations did not principally differ in both species. The species' differences were mainly expressed by phase shifts of about 12 h in the occurrence of maximal and minimal activities according to the different phases of the locomotor activity of the mainly night-active mice and day-active chickens.


Morphological and neurochemical effects of diazepam and phenobarbital on selective culture of neurons from fetal rat brain.
The responses to diazepam (DZ) and phenobarbital (PhB) were studied in enriched neuronal primary cultures from rat embryo hemispheres. Cells were grown in chemically defined medium and the drugs were added for 3 days to cultures, at pharmacologically active concentrations. Following exposure to DZ or to PhB, morphological changes, such as less prominent neuronal processes, were observed in neurons. It was also shown that each drug reduced the specific uptake of 2-deoxy-D-glucose by the cells and interfered with protein and RNA metabolism. It was concluded that both DZ and PhB might affect, at least transiently, the normal growth of neurons in culture.


Are gods and good governments culturally and psychologically interchangeable?
Cognitive by-product theorists maintain that standard cognitive development facilitates the acquisition of religion. Citing secularization, Norenzayan et al. qualify that theory, proposing that gods and good governments are psychologically and culturally interchangeable. That contention, though, occasions questions about the psychological dynamics involved, about what qualifies as religiosity, and about asymmetries between gods and good governments in the face of catastrophes.


Determinants of stress fracture risk in United States Military Academy cadets.
Prior studies have identified some risk factors for stress fracture in athletes and military recruits. To determine whether historical factors, physical measures, biochemical variables of skeletal metabolism, genetic factors, bone density (BMD) and bone size could predict risk of stress fracture over 4 years in physically fit cadets at the US Military Academy (USMA). Baseline surveys, assessments of height, weight, scores on the Army Physical Fitness Test, and peripheral BMD were obtained in all cadets (755 men, 136 women), and central BMD in a subset. Blood samples were analyzed for variables of calcium homeostasis, bone turnover, and selected hormones and genetic factors. Stress fractures were adjudicated by review of orthopedic notes and imaging reports. 5.7% of male and 19.1% of female cadets had at least 1 stress fracture (58% metatarsal and 29% tibial), most within 3 months of entry to USMA. In males, risk of stress fracture was higher in those who exercised <7 h per week during the prior year (RR 2.31; CI 1.29,4.12), and in those with smaller tibial cortical area (RR 1.12; CI 1.03,1.23), lower tibial bone mineral content (RR 1.11; CI 1.03,1.20) and smaller femoral neck diameter (RR 1.35, CI 1.01, 1.81). In women, higher stress fracture risk was seen in those with shorter time since menarche (RR 1.44 per year; CI 1.19, 1.73) and smaller femoral neck diameter (RR 1.16; CI 1.01, 1.33.). Although prior physical training in men, length of prior estrogen exposure in women and leg bone dimensions in both genders played a role, the maximum variance explained by all of these factors was below 10%. We conclude these factors play a minor role in the development of stress fractures in physically fit USMA cadets.


One-Pot Synthesis of Polypyrazoles by Click Reactions.
We developed an efficient one-pot metal-free click polymerization procedure for the synthesis of 3,5-disubstituted polypyrazoles with high yields, high molecular weights, and narrow molecular weight distribution. The method involved two click reactions in a one-pot synthesis. The first reaction was the carbonyl chemistry of "non-aldol" type (condensation reaction of aldehydes with p-toluenesulfonylhydrazide), and the second was a click polymerization reaction of diazo compounds with alkynes. The reactions occurred sequentially by adding the reactants step by step. The diazo compound needed for the second click reaction was generated in situ by the first click reaction. The structures of the polypyrazoles were characterized by IR and 1H NMR analyses. And their thermal properties and solubility were also tested.


Dose-response association of physical activity with acute myocardial infarction: do amount and intensity matter?
The aims of this study were to analyze the dose-response association between leisure time physical activity (PA) practice and myocardial infarction (MI), considering not only the total amount but also the amount of PA at different levels of intensity, and to determine whether these associations were modified by age. In a population-based age- and sex-matched case-control study, all first acute MI patients aged 25 to 74 years were prospectively registered in four Spanish hospitals between 2002 and 2004. Controls were randomly selected from population-based samples recruited during the same period of time. The Minnesota PA questionnaire was administered to assess total energy expenditure in PA and in light-, moderate-, and high-intensity PA. Finally, 1339 cases and 1339 controls were included. The association between PA and MI likelihood was non-linear, with significantly lower MI odds at low practice levels (≥ 500 MET·min/week), lowest odds around 1500 MET·min/week, and a plateau thereafter. Light- (in subjects older than 64 years), moderate-, and high-intensity PA produced similar benefits. Most of the population could reduce their likelihood of MI by engaging in PA at a moderate level of intensity or, in individuals older than 64 years, at a light level of intensity.


Characterization of the novel HLA-C*05:01:72 allele by next generation sequencing.
Full-length sequence of HLA-C*05:01:72 covers the 5'-untranslated region (UTR), all introns and exons and the 3' UTR.


Stroke and transient ischaemic attack in 18 neurology departments from two Italian Regions: the SINPAC database.
This observational prospective multicentre study aims to describe a hospital-based database collecting information about clinical features, management and follow-up of stroke patients. In 18 neurological departments (mostly first-referral) in Piedmont and the Aosta Valley, Italy, between May and July 1999, 604 consecutive patients (97 TIA, 443 ischaemic, and 64 haemorrhagic stroke) were studied. Ischaemic stroke aetiologies were as follows: large-artery atherosclerosis (148), small-artery occlusion (133), cardioembolism (76), other causes (13) and undetermined (73). According to Bamford's classification, 164 were PACI, 126 LACI, 87 TACI and 66 POCI. The diagnostic workup and management of patients is described; only 4% of patients did not receive a CT scan. Four hundred and three patients were discharged to their home, 78 to a rehabilitation unit, 44 to long-term institutional care, 20 to other wards and 59 died while in hospital. After six months, 10 patients were lost to follow-up, 499 were alive and 95 had died. The SINPAC database allows for evaluation of current practice of care in a first-referral stroke population.


Does the Dream of Home Ownership Rest Upon Biased Beliefs? A Test Based on Predicted and Realized Life Satisfaction.
The belief that home ownership makes people happy is probably one of the most widespread intuitive theories of happiness. However, whether it is accurate is an open question. Based on individual panel data, we explore whether home buyers systematically overestimate the life satisfaction associated with moving to their privately owned property. To identify potential prediction errors, we compare people's forecasts of their life satisfaction in 5 years' time with their current realizations. We find that home buyers for whom the purchase of the home is a main reason for moving, on average, systematically overestimate the long-term satisfaction gain of living in their dwelling. The misprediction therein is driven by home buyers who follow extrinsically-oriented life goals, highlighting biased beliefs regarding own preferences as a relevant mechanism in the prediction errors.


Pattern and interpretation of hepatitis B virus markers among pregnant women in North East Egypt.
Hepatitis B vaccination of newborns (HBV) and surveillance of pregnant women during antenatal care are complementary to prevent mother to child transmission (MTCT) of HBV infection. The aim was to identify the prevalence and pattern of HBV infection in pregnant women born before and after implementing HBV vaccination of newborn in Egypt. The study included 600 women attended antenatal clinic of the Suez Canal University Hospital, Ismailia, Egypt. All were inquired about risk factors of HBV infection, vaccination, and screened for hepatitis markers. HBsAg carriers were tested for HBeAg, HBeAb, ALT, and HBV DNA. Participants were divided into group 1 of 285 (47.5%) vaccinated women ≤ 25 years, and 315 (52.5%) non-vaccinated > 25 years. The prevalence of HBcAg, HBsAg, and HBsAb were 18.3%, 5.0%, and 30.7%. Of the 110 women exposed to infection, 40 (36.4%) cleared infection, 30 (27.2%) were HBsAg carriers, and 40 (36.4%) showed isolated HBcAb. HBsAg carriers were HBeAg negative, HBeAb positive, and HBV-DNA positive and had high ALT. Group 1 had significantly higher frequency of vaccination-related immunity, lower frequency of isolated HBcAb, and susceptibles than group 2 (44.9%, 3.5%, and 38.6% vs. 4.1%, 9.5%, and 75.9% ). The prevalence of HBV exposure and chronic HBsAb carriers in both groups were close (4.9% and 16.5% for group 1 vs. 5.1% and 20% for group 2, p > 0.05). Although the outcomes of HBV infection were favorable in vaccinated group, chronic HBV represents a potential risk for MTCT that necessitates screening during pregnancy in all public health care settings.


Methicillin-resistant Staphylococcus aureus (MRSA) colonization in patients with spinal cord injury.
Methicillin-resistant Staphylococcus aureus (MRSA) colonization has been a problem in the Rancho Los Amigos Medical Center (RLAMC) since 1978. This study reviews the latest 2 years' use of a protocol to prevent the spread of MRSA while allowing spinal cord injured patients to continue to participate in the rehabilitation program. The protocol included management in a private room, bathing with hexachlorophene, monitoring positive sites and clearing patients after 3 weeks of negative cultures. Clusters of cases were investigated by obtaining nasal cultures from the personnel. Sixty-seven of 584 (11%) SCI patients were colonized from July 1989 to July 1991. The prevalence of MRSA colonization was significantly greater in the pressure ulcer management service (PMS) 49/184 (27%) than in the rehabilitation spinal injury service (SIS) 18/400 (5%). The body sites colonized were wounds (58/67), nares (37/67), throat (30/67), urine (27/67) and perineum (17/67). Oral therapy with combinations of sulfamethoxazole trimethoprim (SXT) or Novobiocin with rifampin together with topical antibiotics (nares and wound sites), used in nine patients with healing wounds or recent flap surgery, resulted in clearing of the colonization in all cases. Identification and treatment of carriers in the personnel and use of preadmission screening cultures for MRSA in patients with pressure ulcers resulted in reduced inpatient admission.


Retinol-binding protein, transthyretin, and C-reactive protein in extremely low birth weight (ELBW) infants.
Vitamin A deficiency reduces retinol binding protein (RBP) but not transthyretin (TTR), while inflammation reduces both RBP and TTR and increases C-reactive protein (CRP), an acute phase reactant. To estimate serum RBP, TTR, and CRP in ELBW infants to test the hypotheses that (a) TTR is a negative acute phase reactant and (b) a higher RBP/TTR ratio or CRP is associated with death/BPD by 36 weeks corrected age. Serum RBP, TTR, and CRP were measured in 79 ELBW infants at 28 days. Area under the curve (AUC) of receiver operating characteristic curve analysis evaluated the predictive value of TTR, the RBP/TTR ratio, and CRP for death/BPD at 36 weeks. (1) TTR inversely correlated with CRP (r=-0.45, p<0.0001) consistent with TTR being a negative acute phase reactant. (2) The RBP/TTR ratio predicted death/BPD (AUC 0.68 (CI 0.57 to 0.78)). (3) CRP strongly predicted death/BPD (AUC 0.85 (CI 0.76 to 0.92)), even after exclusion of sepsis. A higher CRP and RBP/TTR molar ratio on day 28 are associated with death/BPD at 36 weeks in ELBW infants. Lower TTR and maintained RBP/TTR ratios suggest inflammation rather than vitamin A deficiency as the cause for lower serum vitamin A levels in ELBW infants..


Autoradiographic and histopathological studies of boric acid-mediated BNCT in hepatic VX2 tumor-bearing rabbits: Specific boron retention and damage in tumor and tumor vessels.
Hepatoma is a malignant tumor that responds poorly to conventional therapies. Boron neutron capture therapy (BNCT) may provide a better way for hepatoma therapy. In this research, (10)B-enriched boric acid (BA, 99% (10)B) was used as the boron drug. A multifocal hepatic VX2 tumor-bearing rabbit model was used to study the mechanisms of BA-mediated BNCT. Autoradiography demonstrated that BA was selectively targeted to tumors and tumor vessels. Histopathological examination revealed the radiation damage to tumor-bearing liver was concentrated in the tumor regions during BNCT treatment. The selective killing of tumor cells and the destruction of the blood vessels in tumor masses may be responsible for the success of BA-mediated BNCT for liver tumors.


Precision Medicine Approaches When Prostate Cancer Akts Up.
Ipatasertib combined with abiraterone in PTEN-null prostate cancer improved progression-free survival in a randomized phase II study of patients with metastatic castration-resistant prostate cancer (mCRPC), providing clinical evidence of reciprocal activation between the Akt and androgen receptor (AR) pathways. These data revive the rationale for targeting PTEN loss in prostate cancer.See related article by de Bono et al., p. 928.


Efficacy of etanercept for treating the active rheumatoid arthritis: an updated meta-analysis.
To evaluate the efficacy of etanercept (ETA) for treating active rheumatoid arthritis (RA) compared to placebo or methotrexate (MTX). We searched Medline, Cochrane Library and Wiley databases. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to compare efficacy. In total, 12 studies with 3878 active RA patients (including 2046 patients treated with ETA and 1832 patients treated with placebo or MTX) were included. The overall RRs in ACR20, 50 and 70 (20%, 50%, 70% improvement based on the criteria of American Rheumatism Association) were 2.10 (95% CI: 1.45-3.02, P < 0.0001), 2.87 (95% CI: 1.66-4.97, P = 0.0002) and 2.16 (95% CI: 1.49-3.13, P < 0.0001) within 24 weeks, respectively and were 1.19 (95% CI: 1.11-1.28, P < 0.00001), 1.37 (95% CI: 1.22-1.53, P < 0.00001) and 1.57 (95% CI: 1.28-1.92, P < 0.00001) within 1-3 years, respectively. Further, the overall RRs of 25 mg versus 10 mg ETA twice weekly in ACR20, 50 and 70 were 1.10 (95% CI: 1.02-1.19, P < 0.02), 1.37 (95% CI: 0.98-1.92, P < 0.07) and 1.27 (95% CI: 1.02-1.58, P < 0.03), respectively. In active RA patients treated with ETA, there was significantly higher efficacy compared to the treatment of placebo or MTX. High doses of ETA were more effective for active RA patients.


[Use of diafiltration in the lavage of cultures of Leptospira interrogans canicola canicola for the production of vaccine vax-SPIRAL].
It was proposed to substitute the present technology of the lavage operation for a tangential microfiltration system at the lavage stages of the culture of Leptospira interrogans canicola canicola. It was proved that this system may be applied, since no cellular affectation was observed and high pollutant elimination levels were obtained.


Treatment outcomes for Mycobacterium avium complex: a systematic review and meta-analysis.
To evaluate the existing evidence regarding treatment regimens for Mycobacterium avium complex (MAC), a systematic review of the available therapeutic studies was conducted to assess treatment outcomes. A random-effects meta-analysis was used to assess treatment outcomes. Subgroup analyses were also conducted by separating studies based on each characteristic independently. Twenty-eight trials met the inclusion criteria. Our meta-analysis showed that the estimated pooled treatment success rate for patients with MAC disease was 39 % [95 % confidence interval (CI) 38-41 %]. The rates of failure, relapse, death, and default were 27 % (95 % CI 25-29 %), 6 % (95 % CI 5-7 %), 17 % (95 % CI 15-18 %), and 12 % (95 % CI 11-13 %), respectively. The proportion of patients treated successfully did not differ significantly on the basis of the study characteristics. However, studies with treatment regimens containing macrolides had significantly higher pooled success proportions (42 %, 95 % CI 40-44 %) than that of other studies (28 %, 95 % CI 24-32 %). Substantial heterogeneity in the study characteristics prevented more conclusive determination of what factors had the greatest effect on the proportion of patients that achieve treatment success and limited the validity of this analysis. This review underscored the importance of strong patient support and treatment follow-up systems to develop successful MAC treatment programs.


Acute concomitant injury and intoxication in complainants of recent sexual assault: A review.
Sexual assault remains a highly prevalent crime worldwide and has the potential to cause a number of short and longer-term health sequelae. Complainants of recent sexual assault may undergo forensic and/or medical examinations for medical treatment or evidence collection, or both. However, the frequency and severity of acute health concerns requiring medical intervention in these patients at the time of examination is not well understood and has implications for their clinical care and safety. To examine the frequency and severity of acute concomitant health concerns at the time of forensic examination following an allegation of recent sexual assault in post-pubertal (age >13 years) individuals, through a review of existing literature. Concomitant health concerns considered in this review include ano-genital and extra-genital injury, and acute substance intoxication. Four online databases (PubMed, Ovid Medline, CINAHL, Embase) were systematically searched with key terms regarding the topics of sexual assault, forensic examination, injury and intoxication. Articles were assessed for relevance based on inclusion and exclusion criteria. Of 562 titles, 53 full-text publications met the inclusion criteria. Frequency of ano-genital and extra-genital injury was highly variable across studies, and severity was inconsistently assessed and rarely reported. Medical treatment or transfer to acute care settings was more commonly required for extra-genital injuries. Non-fatal strangulation (NFS) was found to represent an increasingly frequent feature of sexual assault cases. NFS complainants often exhibit signs and symptoms of potentially lethal complications requiring urgent review in acute care settings. Substance use around the time of sexual assault was commonly reported by patients and detected in toxicological screens, and could have significant implications on patient and staff safety at the time of examination. The findings of this review highlight the clinical significance of acute concomitant health concerns following an allegation of recent sexual assault. Ano-genital and extra-genital injury, NFS and both voluntary and involuntary substance use may be more frequent and severe than previously understood. Further investigation into the assessment and management of these acute health needs is required to elucidate their clinical significance and inform evidence-based care for complainants of sexual assault.


Combination Nanopreparations of a Novel Proapoptotic Drug - NCL-240, TRAIL and siRNA.
To develop a multifunctional nanoparticle system carrying a combination of pro-apoptotic drug, NCL-240, TRAIL [tumor necrosis factor-α (TNF-α)-related apoptosis-inducing ligand] and anti-survivin siRNA and to test the combination preparation for anti-cancer effects in different cancer cells. Polyethylene glycol-phosphoethanolamine (PEG-PE) - based polymeric micelles were prepared carrying NCL-240. These micelles were used in combination with TRAIL-conjugated micelles and anti-survivin siRNA-S-S-PE containing micelles. All the micelles were characterized for size, zeta potential, and drug encapsulation efficiency. Different cancer cells were used to study the cytotoxicity potential of the individual as well as the combination formulations. Other cell based assays included cellular association studies of transferrin-targeted NCL-240 micelles and study of cellular survivin protein downregulation by anti-survivin siRNA-S-S-PE containing micelles. NCL-240 micelles and the combination NCL-240/TRAIL micelles significantly increased cytotoxicity in the resistant strains of SKOV-3, MCF-7 and A549 as compared to free drugs or single drug formulations. The NCL-240/TRAIL micelles were also more effective in NCI/ADR-RES cancer cell spheroids. Anti-survivin siRNA micelles alone displayed a dose-dependent reduction in survivin protein levels in A2780 cells. Treatment with NCL-240/TRAIL after pre-incubation with anti-survivin siRNA inhibited cancer cell proliferation. Additionally, a single multifunctional system composed of NCL-240/TRAIL/siRNA PM also had significant cytotoxic effects in vitro in multiple cell lines. These results demonstrate the efficacy of a combination of small-molecule PI3K inhibitors, TRAIL, and siRNA delivered by micellar preparations in multiple cancer cell lines.


Simultaneous separation of five fluoroquinolone antibiotics by capillary zone electrophoresis.
A novel methodology has been developed for simultaneous separation of ciprofloxacin (CPFLX), gatifloxacin (GTFLX), levofloxacin (LVFLX), moxifloxacin (MFLX) and sparfloxacin (SPFLX) fluoroquinolone antibiotics (FQs), using capillary zone electrophoresis (CZE) with UV detection at 282 nm. Electrolyte composition was optimized through the variation of the Tris/hydrochloride and sodium tetraborate buffer mixture. The electrolyte consisted of a 25 mmol L(-1) Tris/hydrochloride and 15 mmol L(-1) sodium tetraborate buffer mixture resulting in pH 8.87. All analytes were separated in less than 3 min. The proposed method was applied to the separation of FQs in pharmaceutical formulations, and the assay results were within 95-105% of the label claim.


Hepatolithiasis associated with cholangiocarcinoma.
Hepatolithiasis is a risk factor for cholangiocarcinoma. It is difficult to make an accurate diagnosis before treatment. In a retrospective study, we identified characteristic clinical features of 103 patients with hepatolithiasis (group H) and 10 patients with hepatolithiasis associated with cholangiocarcinoma (group HC), and examined the methods for diagnosis and treatment. The main symptoms were abdominal pain, fever, and jaundice, although few patients in group HC had jaundice. The incidence of abnormal serum levels of carcinoembryonic antigen (CEA) in group HC was higher than in group H. The incidence of cholangiocarcinoma in cases in which most of the stones were present in the intrahepatic ducts of the left lobe (type I-L) was higher than the incidence in the other patients. Of the patients who underwent portography in group HC, portal veins in the portion of the liver containing the cholangiocarcinoma were not seen, and this region was atrophic in the operative specimens. The incidence of portal obstruction in portograms in group HC was higher than that in group H. The possibility of carcinoma should be kept in mind if there are high levels of CEA, if the location of the stones is classified as type I-L, or if portal veins cannot be seen on portograms. In such patients, liver resection should be considered because there may be undiagnosed cholangiocarcinoma.


Cardiovascular Health, Erectile Dysfunction, and Testosterone Replacement: Controversies and Correlations.
Erectile dysfunction and cardiovascular disease share a similar underlying pathophysiology, and low serum testosterone, known as hypogonadism, is a significant player in both conditions. Hypogonadism is a known risk factor for cardiovascular events and worsened mortality, thus influencing physicians to recommend testosterone replacement in hypogonadal men. However, at least 4 recent reports suggest that testosterone replacement may worsen cardiovascular risk, heightening hesitancy in the medical community to treat patients with hypogonadism with testosterone. This review highlights the triad of cardiovascular disease, erectile dysfunction, and testosterone therapy and provides the physician with some guiding principles for navigating these recent concerns.


Quality of care indicators and their related outcomes: a population-based study in prostate cancer patients treated with radiotherapy.
We describe variations across the regional cancer centres in Ontario, Canada for five prostate cancer radiotherapy (RT) quality indicators: incomplete pre-treatment assessment, follow-up care, leg immobilization, bladder filling, and portal film target localization. Along with cancer centre volume, we examined each indicator's association with relevant outcomes: long-term cause-specific survival, urinary incontinence, and gastrointestinal and genitourinary late morbidities. We conducted a population-based retrospective cohort study of 924 prostate cancer patients diagnosed between 1990 and 1998 who received RT within 9 months of diagnosis. Data sources included treating charts and registry and administrative data. The associations between indicators and outcomes were analysed using regression techniques to control for potential confounders. Practice patterns varied across the regional cancer centres for all indicators (p<0.0001). Incomplete pre-treatment assessment was associated with worse cause-specific survival although this result was not significant when adjusted for confounding (adjusted RR=1.78, 95% CI=0.79-3.98). Treatment without leg immobilization (adjusted RR=1.72, 95% CI=1.16-2.56) and with an empty bladder (adjusted RR=1.98, 95% CI=1.08-3.63) was associated with genitourinary late morbidities. Treatment without leg immobilization was also associated with urinary incontinence (adjusted RR=2.18, 95% CI=1.23-3.87). We documented wide variations in practice patterns. We demonstrated that measures of quality of care can be shown to be associated with clinically relevant outcomes in a population-based sample of prostate cancer patients.


Comparative Genomic Analysis and In Vivo Modeling of Streptococcus pneumoniae ST3081 and ST618 Isolates Reveal Key Genetic and Phenotypic Differences Contributing to Clonal Replacement of Serotype 1 in The Gambia.
Streptococcus pneumoniae serotype 1 is one of the leading causes of invasive pneumococcal disease (IPD) in West Africa, with ST618 being the dominant cause of IPD in The Gambia. Recently however, a rare example of clonal replacement was observed, where the ST3081 clone of serotype 1 replaced the predominant ST618 clone as the main cause of IPD. In the current study, we sought to find the reasons for this unusual replacement event. Using whole-genome sequence analysis and clinically relevant models of in vivo infection, we identified distinct genetic and phenotypic characteristics of the emerging ST3081 clone. We show that ST3081 is significantly more virulent than ST618 in models of invasive pneumonia, and is carried at higher densities than ST618 during nasopharyngeal carriage. We also observe sequence type-specific accessory genes and a unique sequence type-specific fixed mutation in the pneumococcal toxin pneumolysin, which is associated with increased hemolytic activity in ST3081 and may contribute to increased virulence in this clone. Our study provides evidence that, within the same serotype 1 clonal complex, biological properties differ significantly from one clone to another in terms of virulence and host invasiveness, and that these differences may be the result of key genetic differences within the genome.


The behavior of rats in response to changes in the light regime and administration of melatonin.
This report describes studies of the effects of shifts in the daily light/dark rhythm and administration of different doses of melatonin on the behavior of rats with different activity in the open field test. Experiments were performed on 172 Wistar rats kept in a natural or an inverted light/dark regime. Groups of rats received 1 ml of physiological saline or melatonin (1 or 2 mg/kg, i.p.) or were not injected. Inversion of the light/dark regime led to a shift in the rhythm of movement activity and eliminated differences between measures of daytime and night-time activity in control rats not given injections. The effect of melatonin on the movement activity of rats in conditions of natural and inverted light regimes depended on the dose given, the time of administration, and the initial characteristics of the animals' behavior. The data obtained here show that use of melatonin to correct impairments induced by the shift in the light/dark cycle should take consideration of the individual behavioral characteristics of the subjects.


Evidence for a near UV-induced photoproduct of 5-hydroxymethylcytosine in bacteriophage T4 that can be recognized by endonuclease V.
Non-photoreactivable endonuclease V-sensitive sites have been detected in the DNA of wild type bacteriophage T4 irradiated with near UV light (320 nm). Such sites were not detected in the DNA of (a) wild type T4 irradiated with far UV (254 nm) or (B) in T4 mutants in which non-glucosylated 5-hydroxy-methylcytosine (5HMC) or cytosine replaces glucosylated 5HMC normally present in T4, irradiated with 320 nm or 254 nm light. Although the non-photoreactivable sites accounted for approximately 50% of the endonuclease V-sensitive sites in the DNA of glucosylated T4 irradiated with near UV, there was very little difference in the sensitivities of T4 containing glucosylated 5HMC, non-glucosylated 5HMC and cytosine to near UV (313 nm). We propose that the photoproduct responsible for the non-photoreactivable, but endonuclease V-sensitive, sites in glucosylated DNA is formed from glucosylated 5HMC and that a similar photoproduct is formed from non-glucosylated 5HMC or cytosine in the appropriate phage strains. We further propose that the glucosylated 5HMC photoproduct is non-photoreactivable whereas the cytosine and non-glucosylated 5HMC photoproducts are photoreactivable and are therefore possibly cyclobutane dimers.


Protein kinase C epsilon confers resistance of MCF-7 cells to TRAIL by Akt-dependent activation of Hdm2 and downregulation of p53.
Protein kinase C epsilon (PKC epsilon ) acts as an antiapoptotic protein and inhibits tumor necrosis factor-alpha (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in MCF-7 breast cancer cells. Members of the TNF receptor superfamily trigger apoptosis independent of the tumor suppressor protein p53, which primarily affects DNA damage-induced apoptosis. We have previously shown that PKC epsilon acts upstream of Akt to inhibit receptor-initiated cell death. Since Akt can regulate p53, we have examined the involvement of p53 in PKC epsilon-mediated TRAIL resistance. Overexpression of PKC epsilon in MCF-7 cells (MCF-7/PKC epsilon ) caused a decrease in p53 and an increase in human homolog of murine double minute 2 (Hdm2) and phospho-Hdm2. Depletion of p53 by siRNA attenuated, whereas depletion of Hdm2 enhanced TRAIL-mediated apoptosis. Knockdown of Akt decreased Hdm2 phosphorylation, increased p53 level and potentiated TRAIL-induced cell death. Depletion of epsilon from MCF-7 cells caused an increase in p53, whereas knockdown of p53 caused a decrease in Bid mRNA. Depletion of Akt from MCF-7/PKC epsilon cells resulted in an increase in p53 and Bid. These results suggest that PKC epsilon mediates TRAIL resistance by Akt-mediated phosphorylation of Hdm2 resulting in suppression of p53 expression and downregulation of Bid in MCF-7 breast cancer cells.


Comparative protein profiles of the Ambrosia plants.
Ragweed pollen is primarily responsible for the hay fever allergies of sufferers throughout the world. A proteome study of three ragweed plants (Ambrosia artemisiifolia, Ambrosia trifida, and Ambrosia psilostachya) was undertaken to document and compare their protein profiles. Proteins extracted from the pollen of the three plants were subjected to one dimensional electrophoresis followed by tandem liquid chromatography-mass spectroscopy. Peptide sequence mapping permitted discovery of proteins not previously reported for all three plants and 45% of the identified proteins were shared by all three of them. Application of stringent criteria revealed not only a majority of known allergens for short ragweed but also allergens not previously reported for the other two plants. Additionally, potentially allergy inducing enolases are reported for the three plants. These results suggest that all three ragweed plants could contribute to the allergy malady.


Making sense of medical paternalism.
Why do we regulate the substances we can ingest, the advisors we can hear, and the products we can buy far more than similarly-important non-health choices? I review many possible arguments for such paternalistic policies, as well many possible holes in such arguments. I argue we should either be clearer about what justifies our paternalism, or we should back off and be less paternalistic.


Improved band shift assay for the simultaneous analysis of protein-DNA interactions and enzymatic functions of DNA polymerases.
A simple method to assay the major properties of DNA polymerases such as template binding, polymerase and exonuclease activities in one step is exemplified with the DNA polymerases of E. coli, bacteriophage T4 and herpes simplex virus. Combining the advantages of the band-shift assay with the resolving power of polyacrylamide gradient gel electrophoresis, the procedure is particularly useful for a rapid functional analysis of mutant polymerases as well as inhibitors of DNA replication.


Glucose test strips with the largest linear range made via single step modification by glucose oxidase-hexacyanoferrate-chitosan mixture.
We report on the amperometric second-generation glucose test strips with the linear calibration range covering blood glucose concentrations. Chitosan membrane was used for immobilization of both enzyme and mediator in a single step. Optimal chitosan concentration in membrane-forming mixture corresponds to the highest enzyme activity and dramatically improved mediator adsorption in final membrane. On one hand, the immobilized glucose oxidase activation with an increase of the chitosan polymer content in the membrane has been noticed. On the other hand, positively charged chitosan matrix retains mediator (hexacyanoferrate (III) ion) in the membrane, due to its negative charge. Additionally, the excessive adsorption of the mediator on screen-printed electrodes coated with membranes was proved by means of cyclic voltammetry and impedance spectroscopy. Glucose test strips have been elaborated via single-step modification of the sensor support with the enzyme-mediator-polymer mixture. Apparently, the record linear calibration range from 1 mM to 50 mM glucose was achieved recording amperometric response at 5th second after potential was applied. The elaborated test strips have been validated through analysis of standard serum and blood samples. In whole blood test strips keep 84-98% of their sensitivity in buffer solution.


Molecular characterization of human calicivirus associated with acute diarrheal disease in Mexican children.
Human caliciviruses (HuCV) are emerging enteric pathogens that are a common cause of diarrhea in humans worldwide. Due to the paucity of information on the molecular characterization of HuCV circulating in Mexico, the aim of this work was to investigate the diversity and molecular epidemiology of the HuCV infection associated with acute diarrheal disease in Mexican children aged up to 5 years. Of the 131/414 (32%) HuCV positive-specimens analyzed, 128 were identified as Norovirus (NoV) and three as Sapovirus (SaV). Of the NoV positive specimens, 118/128 (92%) were NoV GII and 10/128(8%) were untypeable by RT-PCR in both polymerase and capsid genes, whereas one SaV isolate was further confirmed by sequencing as GI.2. Phylogenetic analysis based on polymerase partial gene sequences from 89/131 (68%) HuCV isolates showed that 86/89 (97%) belong to NoV GII.4 with three main variant clusters of this genotype, 2/89 (2%) to NoV GII.2, and 1/89 (1%) to SaV GI.2. Furthermore, partial sequencing of the capsid gene VP1 of 63/131 (48%) strains indicated that 61/63 (97%) correlated with NoV GII.4, whereas only 2/63 (3%) clustered to NoV GII.2. HuCV infections were detected throughout the year, and the highest number of cases positive for NoV was found in children between 7 and 18 months of age (60%). This study highlights the usefulness of analyzing both polymerase and capsid genes for molecular characterization of HuCV and demonstrates the relatedness and predominance of NoV GII.4 with acute diarrheal disease in young Mexican children, thus contributing to better understanding of the molecular epidemiology of this disease.


Production and characterization of an extracellular polysaccharide from Streptomyces violaceus MM72.
The isolation, optimization, purification and characterization of an extracellular polysaccharide (EPS) from a marine actinobacterium, Streptomyces violaceus MM72 were investigated. Medium composition and culture conditions for the EPS production by S. violaceus MM72 were optimized using two statistical methods: Plackett-Burman design applied to find the key ingredients and conditions for the best yield of EPS production and central composite design used to optimize the concentration of the three significant variables: glucose, tryptone and NaCl. The preferable culture conditions for EPS production were pH 7.0, temperature 35°C and NaCl concentration 2.0% for 120h with fructose and yeast extract as best carbon and nitrogen sources, respectively. The results showed that S. violaceus MM72 produced a kind of EPS having molecular weight of 8.96×10(5)Da. In addition, the EPS showed strong DPPH radical-scavenging activity, superoxide scavenging and metal chelating activities while moderate inhibition of lipid peroxidation and reducing activities determined in this study. These results showed the great potential of EPS produced by S. violaceus MM72 could be used in industry in place of synthetic compounds. The EPS from S. violaceus MM72 may be a new source of natural antioxidants with potential value for health, food and therapeutics.


PERK inhibition prevents tau-mediated neurodegeneration in a mouse model of frontotemporal dementia.
The PERK-eIF2α branch of the Unfolded Protein Response (UPR) mediates the transient shutdown of translation in response to rising levels of misfolded proteins in the endoplasmic reticulum. PERK and eIF2α activation are increasingly recognised in postmortem analyses of patients with neurodegenerative disorders, including Alzheimer's disease, the tauopathies and prion disorders. These are all characterised by the accumulation of misfolded disease-specific proteins in the brain in association with specific patterns of neuronal loss, but the role of UPR activation in their pathogenesis is unclear. In prion-diseased mice, overactivation of PERK-P/eIF2α-P signalling results in the sustained reduction in global protein synthesis, leading to synaptic failure, neuronal loss and clinical disease. Critically, restoring vital neuronal protein synthesis rates by inhibiting the PERK-eIF2α pathway, both genetically and pharmacologically, prevents prion neurodegeneration downstream of misfolded prion protein accumulation. Here we show that PERK-eIF2α-mediated translational failure is a key process leading to neuronal loss in a mouse model of frontotemporal dementia, where the misfolded protein is a form of mutant tau. rTg4510 mice, which overexpress the P301L tau mutation, show dysregulated PERK signalling and sustained repression of protein synthesis by 6 months of age, associated with onset of neurodegeneration. Treatment with the PERK inhibitor, GSK2606414, from this time point in mutant tau-expressing mice restores protein synthesis rates, protecting against further neuronal loss, reducing brain atrophy and abrogating the appearance of clinical signs. Further, we show that PERK-eIF2α activation also contributes to the pathological phosphorylation of tau in rTg4510 mice, and that levels of phospho-tau are lowered by PERK inhibitor treatment, providing a second mechanism of protection. The data support UPR-mediated translational failure as a generic pathogenic mechanism in protein-misfolding disorders, including tauopathies, that can be successfully targeted for prevention of neurodegeneration.


Climb up! Head up! Climbing improves posture in Parkinson's disease. A secondary analysis from a randomized controlled trial.
To investigate the effect of sport climbing on a biomechanical marker of axial posture in patients with Parkinson's disease, as well as its association with age, body mass index and health-related quality-of-life outcome measures. Pre-planned secondary analysis of our randomized controlled, semi-blind trial (unblinded patients, blinded assessors) comparing sport climbing to unsupervised exercise. Single-centre study conducted at the Department of Neurology of the Medical University of Vienna, Austria. Forty-eight Parkinson's disease patients (aged 64 ± 8 years, Hoehn & Yahr stage 2-3) were included. Sport climbers (n = 24) followed a 12-week, 90 min/week supervised top-rope sport climbing course in an indoor climbing gym. The unsupervised training group (n = 24) independently followed the 'European Physiotherapy Guidelines for Parkinson's Disease' and World Health Organization recommendations for an active lifestyle for 12 weeks. Posture was assessed with the horizontal distance of the seventh cervical vertebra to the wall at baseline and after the intervention. Participating in the sport climbing group significantly predicted the biomechanical marker of axial posture (P = 0.044). The improvement in the biomechanical marker did not affect the quality of life, depression, fatigue, physical activity or fear of falling. Participants in the sport climbing group showed a significantly decreased horizontal distance of the seventh cervical vertebra to the wall after the intervention (-1.7 cm (95%CI [-2.6, -0.8]). In the unsupervised training group, no difference was found (-0.5 cm; 95%CI -1.3, 0.2]). We conclude that sport climbing improves a biomechanical marker of axial posture in Parkinson's disease.


Signet-ring cell carcinoma of the prostate effectively treated with maximal androgen blockade.
Primary signet-ring cell carcinoma (SRCC) of the prostate is very rare and has a poor prognosis, even when treated with aggressive therapy. We report herein a case of a 72-year-old man with prostatic SRCC. The patient had a tumor that extended directly to the rectum. Maximal androgen blockade was started and 20 months later, the patient was alive without evidence of recurrence. The present case of prostatic SRCC responded well to medical therapy, however, tumors can recur after a long period of time. Therefore, adjuvant therapy is recommended.


Identification and developmental expression of Ci-isl, a homologue of vertebrate islet genes, in the ascidian Ciona intestinalis.
Here we describe the cloning and expression pattern of Ci-isl, a homologue of vertebrate genes, in the ascidian. Early in development, Ci-isl expression occurs in the primordia of palps and brain vesicle, then in the tailbud embryo it is transiently extended to the notochord cells. At larva stage, the expression is down-regulated in the notochord, and it persists predominantly in the compartments of the nervous system. These observations indicate that also in invertebrates, islet genes show an expression pattern during differentiation of the nervous system.


Interleukin-2 levels are elevated in the bone marrow serum of patients with mutilans-type rheumatoid arthritis.
In order to investigate the pathogenesis of mutilans-type rheumatoid arthritis (RA), we measured cytokine levels in the bone marrow serum of patients with RA. We studied 35 patients with non-mutilans RA, 19 with mutilans RA, and 20 patients with osteoarthritis (OA) undergoing joint surgery. At the time of surgery, iliac bone marrow and peripheral blood were sampled from all 74 patients and cytokine levels measured. The serum levels of five cytokines (IL-1beta, IL-2, IL-3, IL-6 and GM-CSF) were measured by ELISA. Haematologic and inflammatory factors were also measured. Levels of IL-2, IL-6 and GM-CSF in bone marrow serum were significantly higher in all RA patients than in those with OA. Mean (+/-SD) IL-2 levels were significantly higher in patients with mutilans-type RA (309.8+/-686.3 pg/ml) than in patients with other types of RA (66.5+/-173.1 pg/ml; P<0.01). IL-2 was detected significantly more often in patients with mutilans-type RA than in patients with other types of RA (P < 0.01). Inflammatory factors were higher in all RA groups than in OA patients. However, the haematologic and immunologic variables were no different between mutilans RA and other types of RA. No correlations were observed between IL-1beta, IL-2, IL-3, IL-6 and GM-CSF levels and these laboratory variables. In patients with mutilans-type RA, IL-2 levels in the bone marrow serum were significantly higher than in patients with other types of RA or with OA. This elevation does not appear to be related to systemic inflammation, as there was no correlation with other inflammatory factors.


P27Kip1 is down-regulated in the endometrium of women with endometriosis.
To evaluate p27 protein expression in the endometrium of women with endometriosis. Transversal case-control study. Endometriosis Unit, Federal University of São Paulo, Brazil. Thirteen patients with stage I/II endometriosis, five with stage III/IV endometriosis, and 11 control subjects. Endometrial biopsies were obtained from patients with proven endometriosis and women without disease at laparoscopy. P27 protein was immunolocalized in the biopsy tissues and quantified by light microscopy. Immunostaining scores of glandular and stromal cells in endometrial biopsies obtained from patients with confirmed endometriosis compared with those of healthy control women with normal pelvis at laparoscopy. The staining scores of stage I/II and stage III/IV patients and of both patient groups and the control group were compared. The level of p27 protein expression observed in the control group, both in the stroma and in the endometrial glands, was significantly different from that observed in the endometriosis patient groups. Significant differences in p27 protein expression levels in the glandular epithelium and stroma were not observed among groups of patients with endometriosis. The decreased level of p27 protein in the endometrium of women with endometriosis suggests that cell cycle alterations in the endometrial mucosa may be involved in the pathogenesis of this disease.


Synthesis of a paclitaxel isomer: C-2-acetoxy-C-4-benzoate paclitaxel.
A synthesis of the C-2-acetoxy-C-4-benzoate paclitaxel 2 is described. This analog has the substituents at C-2 and C-4 transposed. The key steps in the synthesis include the sequential use of Red-Al as reducing agent for the regioselective reduction of the C-2 benzoate and the C-4 acetoxy within the baccatin core. Iso-paclitaxel 2 was considerably less potent than paclitaxel in tubulin polymerization and in vitro cytotoxicity assays.


Outpatient prescription of oral antibiotics in a training hospital in Turkey: trends in the last decade.
The aim was to evaluate the changing trends in outpatient prescription of oral antibiotic forms at a Training Hospital in the last decade. All the outpatient prescriptions during April and May 2004 were evaluated. The diagnosis, the department of the prescriber, the count and generic name of each prescribed antibiotic were all noted. Of the 33,491 outpatient prescripitions, 14.9% included antibiotic (n=5004). The pediatric clinics (26.4%), Ear, Nose and Throat department (13.7%), and the department of Gyneacology and Obstetrics (10.8%) were the leading departments in antibiotic prescriptions. Upper respiratory tract infections (45.4%), urinary tract infection (11.4%) and lower respiratory tract infections (4.2%) shared the first lines of diagnosis stated. Of the antibiotic prescriptions, 96.3% included oral forms. Co-amoxiclav (26.4%), quinolones (11.7%) and cephalosporins (16.5%) were the most frequently prescribed antibiotics. Percent of antibiotic prescriptions based on microbial sensitivity test results was 7.1%. Compared with the results of the study carried out 11 years ago; though co-amoxiclav is still the most frequently prescribed antibiotic, many other changes have been observed in antibiotic prescription attitudes.


Treatment of a mandibular discontinuity defect by using a fibula free flap and an implant-supported fixed complete denture fabricated with a PEKK framework: A clinical report.
This clinical report describes the rehabilitation of a patient with a history of mandibulectomy that involved the use of a fibula free flap and an implant-supported fixed complete denture. A recently introduced material, polyetherketoneketone (PEKK), was used as the framework material for the prosthesis, and the treatment produced favorable esthetic and functional results.


The impact of patient-generated contextual data on communication in clinical practice: A qualitative assessment of patient and clinician perspectives.
Effective communication is integral to patient-centered care, yet external pressures can impede the ability to discuss important topics. One strategy to facilitate communication is pre-visit collection and sharing of patient contextual data (PCD), including life circumstances such as their beliefs, needs, and concerns. To understand how patients and care team members perceive the electronic collection of PCD and its impact on communication in the context of a large academic health system that implemented PatientWisdom, a new technology that elicits PCD from patients and integrates within the electronic health record (EHR). We conducted focus groups with patients (n = 26) and semi-structured interviews with primary care team members (n = 20). Qualitative analysis of focus group/interviews included an iterative and reflexive inductive technique to uncover emergent themes. Four themes were reflected among both patient and care team: (1) the technology enhances the patient's voice; (2) the technology creates a safe space for patients to share sensitive topics; (3) PCD facilitates rapport not only between patient and provider but the entire care team; (4) PCD aligns patient and clinician goals. Two unique themes emerged among patients: (1) PCD provides opportunity for reflection; (2) PCD humanizes patients in the clinical context. One theme was evident in provider comments: collecting PCD may potentially undermine trust if not reviewed by clinical teams. PCD collected directly from patients and available within the EHR was seen by patients and care team members as beneficial to communication. PCD collection supports a paradigm shift towards coproduction of health information and a shared responsibility for information gathering but requires investment from patients and care team to ensure the data are effectively utilized. PCD may be useful for team-based care, enabling physicians and non-physician staff to more quickly and responsively connect with patients.


Interspecies comparison of human and murine scleroderma reveals IL-13 and CCL2 as disease subset-specific targets.
Development of personalized treatment regimens is hampered by lack of insight into how individual animal models reflect subsets of human disease, and autoimmune and inflammatory conditions have proven resistant to such efforts. Scleroderma is a lethal autoimmune disease characterized by fibrosis, with no effective therapy. Comparative gene expression profiling showed that murine sclerodermatous graft-versus-host disease (sclGVHD) approximates an inflammatory subset of scleroderma estimated at 17% to 36% of patients analyzed with diffuse, 28% with limited, and 100% with localized scleroderma. Both sclGVHD and the inflammatory subset demonstrated IL-13 cytokine pathway activation. Host dermal myeloid cells and graft T cells were identified as sources of IL-13 in the model, and genetic deficiency of either IL-13 or IL-4Rα, an IL-13 signal transducer, protected the host from disease. To identify therapeutic targets, we explored the intersection of genes coordinately up-regulated in sclGVHD, the human inflammatory subset, and IL-13-treated fibroblasts; we identified chemokine CCL2 as a potential target. Treatment with anti-CCL2 antibodies prevented sclGVHD. Last, we showed that IL-13 pathway activation in scleroderma patients correlated with clinical skin scores, a marker of disease severity. Thus, an inflammatory subset of scleroderma is driven by IL-13 and may benefit from IL-13 or CCL2 blockade. This approach serves as a model for personalized translational medicine, in which well-characterized animal models are matched to molecularly stratified patient subsets.


[Intrauterine infection in relation to the frequence of prematurity and congenital malformations].
In order to find the relationship between intrauterine infection with frequency of prematurity and of congenital malformations, 1,016 newborns were studied and were divided into four groups: 324 normal babies, 606 prematures, 44 with malformations and 42 infected patients; the latter were confirmed through titration of serum antibodies. The first index of infection was the concentration of IgM greater than or equal to 28 mg. %; thus, the first groups showed evidence of infection in 0.9%; the second in 11%; the third in 40.9% and the fourth, in 100%.


Evaluation of prostate cancer based on MALDI-TOF MS fingerprinting of nanoparticle-treated serum proteins/peptides.
The serum MALDI-TOF MS spectrum includes signals for serum proteins and peptides between 1000 and 12,000 Da in size, presenting a fingerprint-like pattern. However, whole serum MALDI-TOF MS signals are complex and prejudiced for data analysis. Pre-treatment with specific nanomaterials can simplify the mass spectrum while retaining the characteristics of the fingerprint pattern. In the present study, we used hydrophilic interaction chromatography nanoparticles (HICNPs) to enrich proteins and peptides in serum from a large number prostate cancer samples and controls. After pre-treatment with HICNPs, the serum MALDI-TOF MS signals for samples were simpler, with more analysable fingerprint-like patterns. Principal component analysis and partial least squares discriminant analysis of the samples demonstrated a significant difference in the MALDI-TOF signals between prostate cancer and controls, with an analytical accuracy of 77%, approaching that of methods based on prostate-specific antigen. Due to the low cost and high flux, MALDI-TOF MS fingerprinting can be used in large-scale evaluation of various cancers, including prostate cancer.


Using Modified Skin-Stretching Technique as an Alternative Solution for the Closure of Moderate and Extensive Skin Defects.
External skin-stretching devices have been developed and used for wound closure since 1970s. Devices such as Miami STAR®, SureClosure®, TopClosure®, and WiseBand® have their own advantages and disadvantages. The modified external skin-stretching technique of this case series study has the advantage to improve tension distribution and simplified the application. Between January 2014 and June 2017, 20 patients were treated with the modified external skin-stretching device for the closure of the skin defects of the trunk (n = 6) and extremities (n = 14). Skin defects ranged from 8 × 5 to 19 × 16 cm achieved primary closure with the utilization of the modified skin-stretching device without major complications. Subsequent minor revisions were performed under local anesthesia between 6 and 12 months postoperatively. The modified skin-stretching device utilized biomechanical properties and mechanical creep of skin tissue to achieve a reliable and effective primary closure for moderate to extensive skin defects. Therefore, this modified external skin-stretching technique provided, in the appropriate setting, an effective alternative to skin grafts or free flaps.


Reliability of the Participation and Sensory Environment Questionnaire: Community Scales.
The Participation and Sensory Environment Questionnaire (P-SEQ): Community Scales is a parent report questionnaire designed to examine the impact of the sensory environment on participation within community activities for children with autism spectrum disorder (ASD). This study used a cross sectional quantitative design to establish the reliability and discriminate validity of the P-SEQ: Community Scales. This study established the initial reliability of the questionnaire including internal consistency of 0.98 test-retest reliability of 0.76. The P-SEQ: Community Scales demonstrated significant differences in item distribution for children without ASD as compared to those with ASD, an essential aspect of construct validity. The results of this study indicate that the questionnaire is a reliable tool that can be used to assess the impact of sensory environment's impact on participation in community activities. Identified barriers can be modified to support participation in community tasks.


RhopH2 and RhopH3 export enables assembly of the RhopH complex on P. falciparum-infected erythrocyte membranes.
RhopH complexes consists of Clag3, RhopH2 and RhopH3 and are essential for growth of Plasmodium falciparum inside infected erythrocytes. Proteins are released from rhoptry organelles during merozoite invasion and trafficked to the surface of infected erythrocytes and enable uptake of nutrients. RhopH3, unlike other RhopH proteins, is required for parasite invasion, suggesting some cellular processes RhopH proteins function as single players rather than a complex. We show the RhopH complex has not formed during merozoite invasion. Clag3 is directly released into the host cell cytoplasm, whilst RhopH2 and RhopH3 are released into the nascent parasitophorous vacuole. Export of RhopH2 and RhopH3 from the parasitophorous vacuole into the infected erythrocyte cytoplasm enables assembly of Clag3/RhopH2/RhopH3 complexes and incorporation into the host cell membrane concomitant with activation of nutrient uptake. This suggests compartmentalisation prevents premature channel assembly before intact complex is assembled at the host cell membrane.


Short-term variation in the level of alpha-fetoprotein in maternal serum.
Serial serum levels of alpha-fetoprotein (AFP) were examined over a 24-h period in six subjects. A short-term variation was demonstrated which was significantly greater than that due to the assay alone, but which showed no particular pattern. These findings may explain why an 'abnormal' AFP level frequently reverts to a 'normal' level on second sampling.


Echocardiographic diagnosis of double-chambered left ventricle.
Double-chambered left ventricle (DCLV) is a rare congenital abnormality in which the left ventricle is divided into two separate chambers by a septum or anomalous muscular structure. The chambers are observed mostly parallel to each other without stenosis, and less frequently in a superior-inferior arrangement. An asymptomatic girl is presented here who was diagnosed with DCLV on echocardiographic examination that was performed for the evaluation of cardiac murmur detected by a pediatrician. She has been followed up without treatment.


Semantic cognition versus numerical cognition: a topographical perspective.
Semantic cognition and numerical cognition are dissociable faculties with separable neural mechanisms. However, recent advances in the cortical topography of the temporal and parietal lobes have revealed a common organisational principle for the neural representations of semantics and numbers. We discuss their convergence and divergence through the prism of topography.


Neurologic Complications in Patients With Left Ventricular Assist Devices.
Left ventricular assist device (LVAD) use has revolutionised the care of patients with advanced heart failure, allowing more patients to survive until heart transplantation and providing improved quality for patients unable to undergo transplantation. Despite these benefits, improvements in device technology, and better clinical care and experience, LVADs are associated with neurologic complications. This review provides information on the incidence, risk factors, and management of neurologic complications among LVAD patients. Although scant guidelines exist for the evaluation and management of neurologic complications in LVAD patients, a high index of suspicion can prompt early detection of neurologic complications which may improve overall neurologic outcomes. A better understanding of the implications of continuous circulatory flow on systemic and cerebral vasculature is necessary to reduce the common occurrence of neurologic complications in this population.


Tribulus terrestris L. induces cell apoptosis of breast cancer by regulating sphingolipid metabolism signaling pathways.
Tribulus terrestris L. (TT) was initially documented in Shen-Nong-Ben-Cao-Jing and has been used for thousands of years in China as a herb to calm liver, dispel melancholy and wind, promote blood circulation, improve eyesight, and relieve itching. Moreover, it was also used to treat breast cancer in ancient China. However, the pharmacological activities of TT extract on breast cancer have received little attention. In this study, we investigated the anti-breast cancer effects and possible mechanisms of action of this herbal drug. Network pharmacology analysis the study of network pharmacology was done to analyze the possibility of TT's anti-breast cancer effect. And then, molecular docking between TT7/TT8 and vascular endothelial growth factor receptor 2 (VEGFR2) were performed by Autodock software as well as the related protein expressions were analyzed by western blot to verify this effect. In vivo experiment: The mouse model of breast cancer was established by injection of 4T1 cells. Then drugs were intragastrically administered to the mice once daily for fourteen days. Body weight, tumor size, and tumor weight were recorded at the end of the experiment. Moreover, tumor inhibitory rate was calculated. Finally, pathological changes and apoptosis of breast cancer tissues were respectively evaluated by HE and Hoechst staining. Proteomics and metabonomics analyses: The tumor tissues were chosen to perform conjoint analysis. Firstly, differential proteins and metabolites were found. Furthermore, the functional analyses of them were analyzed by software. At the last, immunofluorescent staining of SGPP1, SPHK1 and p-SPHK1 in tumor tissue were done. 12 active ingredients of TT, 127 targets of active ingredients, 15,253 targets of breast cancer, 1,225 targets of Ru yan, and 123 overlapping genes were obtained in the network pharmacology study. There was firm conjunction between TT7/TT8 and VEGFR2. Besides, tumor size and weight were markedly reduced in TT groups compared to the model group. The tumor inhibitory rate was more than 26% in TTM group. After drug treatment, many adipocytes and cracks between tumor and apoptosis were discovered. The western blot results showed that TT aqueous extract lowered the levels of VEGFR2, ERK1/2, p-ERK1/2 (Thr202, Tyr204) and Bcl2, while increasing the levels of Bax and the ratio of Bax/Bcl2. Furthermore, 495 differential proteins and 76 differential metabolites were found between TTM and model groups with the sphingolipid metabolism pathway being enriched. At last, TT treatment significantly reduced the levels of SGPP1, SPHK1 and p-SPHK1 in tumor tissue. In conclusion, TT demonstrates therapeutic effects in a mouse model of breast cancer, and its mechanism of action involves the regulations of sphingolipid metabolism signaling pathways. This study lends credence to the pharmacological potential of TT extract as a breast cancer therapy.


A Novel Model of Thyroid Nodule Segmentation for Ultrasound Images.
Ultrasonography is regarded as an effective technique for the detection, diagnosis and monitoring of thyroid nodules. Segmentation of thyroid nodules on ultrasound images is important in clinical practice. However, because in ultrasound images there is an unclear boundary between thyroid nodules and surrounding tissues, the accuracy of segmentation remains a challenge. Although the deep learning model provides an accurate and convenient method for thyroid nodule segmentation, it is unsatisfactory of the existing model in segmenting the margin of thyroid nodules. In this study, we developed boundary attention transformer net (BTNet), a novel segmentation network with a boundary attention mechanism combining the advantages of a convolutional neural network and transformer, which could fuse the features of both long and short ranges. Boundary attention is improved to focus on learning the boundary information, and this module enhances the segmentation ability of the network boundary. For features of different scales, we also incorporate a deep supervision mechanism to blend the outputs of different levels to enhance the segmentation effect. As the BTNet model incorporates the long range-short range connectivity effect and the boundary-regional cooperation capability, our model has excellent segmentation performance in thyroid nodule segmentation. The development of BTNet was based on the data set from Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital and the public data set. BTNet achieved good performance in the segmentation of thyroid nodules with an intersection-over-union of 0.810 and Dice coefficient of 0.892 Moreover, our work revealed great improvement in the boundary metrics; for example, the boundary distance was 7.308, the boundary overlap 0.201 and the boundary Dice 0.194, all with p values <0.05.


Syntheses, Characterizations, and Inhibition Activities Against Coxsackievirus B3 of Iodobenzoic Hydrazide Functionalized Hexamolybdates.
A class of iodobenzoyldiazenido-functionalized POMs (TBA)3 [Mo6O18(=N=NCOAr)] (Ar = Ph-o-I (1); Ph-m-I (2); Ph-p-I (3); Ph-3,4-I2 (4); Ph-2,3,5-I3 (5) (TBA = tetrabutylammonium) were prepared via the refluxing reaction of α-octamolybdates, DCC, and corresponding hydrazides in dry acetonitrile. Their structures were determined by Fourier-transform infrared spectroscopy, ultraviolet-visible spectra, X-ray photoelectron spectroscopy, hydrogen-1 nuclear magnetic resonance, and high-resolution mass spectrometry. Research on the biological activity of title compounds shows that L3, L5, 3, and 5 demonstrate potent inhibitory activity against coxsackievirus B3 and low in vitro cytotoxic activity against Hep-2 cell lines. The covalent linkage between the iodobenzoyldiazenido components and POMs can enhance the molecular inhibitory efficiency of iodobenzohydrazides.


The expression and experience of emotion in schizophrenia: a study of social interactions.
Previous studies on emotional expression and experience in schizophrenia indicate that patients show significantly fewer outward displays of emotion than controls despite similar self-reports of emotional experience in response to various non-social stimuli (e.g. film clips, flavored drinks). However, it is unclear if this disjunction between emotional experience and expression in schizophrenia extends to the interpersonal domain. This study compared 33 patients with schizophrenia and 15 non-psychiatric controls on emotional expression and experience during a social role play. Results showed that patients were significantly less expressive than controls but the two groups reported equal levels of emotional experience. Neither clinical blunting ratings nor behavioral ratings of facial expressivity were related to emotional experience in patients. These results extend prior findings of an expression/experience disjunction in schizophrenia to a social domain. Implications for understanding social dysfunction in schizophrenia and directions for future study are discussed.


Catheter-malposition-induced cardiac tamponade via contrast media leakage during computed tomography study.
We present a rare case of a central venous catheter-malposition-induced life-threatening cardiac tamponade as a result of computed tomography (CT) with contrast enhancement in an infant with a ventricular septal defect and pulmonary atresia after a modified Blalock-Taussig shunt. The diagnosis was confirmed by chest radiographs and CT study with catheter perforation through the right atrial wall and extravasation of the contrast medium into the pericardium, leading to cardiac tamponade and subsequent circulatory collapse. Two hours after successful cardiopulmonary resuscitation, the patient gradually resumed normal hemodynamic status.


Design and rationale of a randomised controlled trial comparing apixaban to phenprocoumon in patients with atrial fibrillation on chronic haemodialysis: the AXADIA-AFNET 8 study.
Patients with end-stage kidney disease requiring maintenance haemodialysis treatment experience a dramatic cardiovascular morbidity and mortality. Due to the high atherosclerotic and arteriosclerotic burden and profound alterations in haemostasis, they frequently suffer and die from both thromboembolic and bleeding events. This is a particular concern in patients on haemodialysis with atrial fibrillation (AF). Controlled trials on the optimal anticoagulation in patients with AF on haemodialysis are not available. The randomised controlled phase IIIb AXADIA-AFNET 8 trial will evaluate the safety and efficacy of the factor Xa inhibitor apixaban in patients with AF requiring haemodialysis. A total of 222 patients will be randomised in an open-labelled, 1:1 design to receive either apixaban 2.5 mg twice daily or dose-adjusted vitamin K antagonist therapy (target international normalised ratio 2.0-3.0). All patients will be treated and followed up for a minimum of 6 months up to a maximum of 24 months. The primary outcome is major or clinically relevant, non-major bleedings or death of any cause. Secondary outcomes include stroke, cardiovascular death and other thromboembolic events, thus exploring the efficacy of apixaban. The first patient was randomised in June 2017. The study protocol was approved by the Ethical Committee of the Landesaertzekammer, Westfalen-Lippe and the Medical Faculty of the University of Muenster, Muenster, Germany (reference number: 2016-598 f-A). Written informed consent will be obtained from all patients prior to study participation, including their consent for long-term follow-up. AXADIA-AFNET 8 is an investigator-initiated trial. Sponsor is AFNET, Muenster, Germany. Study findings will be disseminated to Bristol-Myers Squibb, Munich, Germany, and Pfizer, Berlin, Germany, to the participating centres, at research conferences and in peer-reviewed journals. NCT02933697,Pre-results.


Action of 6-(p-hydroxyphenylazo)-uracil on bacteriophage IG 1.
IG 1, a temperate phage of Bacillus subtilis, is strongly induced from its lysogens by 6-(p-hydroxyphenylazo)-uracil, an azopyrimidine known as selectively inhibiting the B. subtilis DNA polymerase III. IG 1 phages originated either by induction or infection multiply, abundantly, in the presence of that azopyrimidine, in spite of the drastic decline of cell viability. Chloramphenicol completely suppresses the induction effect and also blocks the formation of spontaneously induced phage particles.


Two-step changes in paced QRS morphology suggest capturing at different levels of posterior fascicle fibers during left bundle branch area pacing: A case report.
Two-step changes in paced QRS morphology during the left bundle branch area pacing threshold test. It suggests that capturing occurs at multiple sites of the left bundle branch-Purkinje system.


Enkephalinergic modulation of non-cholinergic transmission in mammalian prevertebral ganglia.
The non-cholinergic excitatory potential elicited in neurons of the isolated inferior mesenteric ganglia was depressed by bath application of Met- or Leu-enkephalin and enhanced by naloxone or naltrexone. The membrane depolarization induced by exogenously applied putative transmitter substance P was not appreciably affected by either enkephalin (Enk) or opiate antagonists. Our results indicate that the non-cholinergic excitatory transmission which may be mediated by substance P in prevertebral ganglia is modulated presynaptically by endogenously released Enk in a manner that may resemble the interaction between these two peptides in the spinal cord.