[Action of natural gamma-interferons on functional activity of phagocytes and antibody synthesis after vaccination].
Natural swine and cattle gamma-IFNs were prepared for trials. One dose of gamma-suiferon contained 1000 IU, that of gamma-boviferon--2000 IU. Three series of researches were carried out to estimate the in vitro and in vivo absorbing activity of phagocytes (monocytes and neutrophiles), their bactericidal ability (on new born pigs and calves, 2 months old animals, sows and cows with calf) and antibodygenesis after immunization of animals by colibacteriosis vaccine. It has been shown in trials that gamma-IFN increased to significant degree (several times, as a rule) the absorbing activity of phagocytes (especially that of monocytes in new-born animals). At the same time bactericidal activity of phagocytes sharply increased--their functional reserve in experimental animals was significantly higher (2-3-times), than in control. Immunization by colinebacteriosis vaccine with additional treatment by homologous gamma-IFN 3-4 times increased antibodygenesis in comparison with control.


The global burden of hepatitis C.
Hepatitis C is of concern both to industrialized and developing countries. Preliminary unpublished estimates of the global burden of disease (GBD) attributable to HCV-related chronic liver disease seem to be substantial. Therefore, the reduction of global mortality and morbidity related to chronic hepatitis C should be a concern to public health authorities, and primary, secondary and tertiary prevention activities should be implemented and monitored in each country, with precise targets set to be reached. In order to decide on national health policies, there is a need to estimate the burden of disease, globally, regionally and nationally. To evaluate the GBD, three components have to be assessed: 1) The global, regional and national burden of morbidity and mortality associated with HCV infection, based on prevalence, incidence, transmission and economics; 2) The natural history of HCV infection, including 'healthy individuals'; and 3) The areas for which more research is needed. A working group was created to assist the World Health organization (WHO) in estimating the GBD associated with HCV infection.


The Lactobacillus flora in vagina and rectum of fertile and postmenopausal healthy Swedish women.
Lactobacillus species are the most often found inhabitants of vaginal ecosystem of fertile women. In postmenopausal women with low oestrogen levels, Lactobacillus flora is diminishing or absent. However, no studies have been performed to investigate the correlation between oestrogen levels and the lactobacilli in the gut. The aim of the present study was to investigate the relation in healthy women between vaginal and rectal microbial flora as well as possible variations with hormone levels. Vaginal and rectal smears were taken from 20 healthy fertile women, average 40 years (range 28-49 years), in two different phases of the menstrual cycle, and from 20 postmenopausal women, average 60 years (range 52-85 years). Serum sex hormone levels were analyzed. Bacteria from the smears isolated on Rogosa Agar were grouped by Randomly Amplified Polymorphic DNA and identified by multiplex PCR and partial 16S rRNA gene sequencing. Lactobacillus crispatus was more often found in the vaginal flora of fertile women than in that of postmenopausal (p = 0.036). Fifteen of 20 fertile women had lactobacilli in their rectal smears compared to 10 postmenopausal women (p = 0.071). There was no correlation between the number of bacteria in vagina and rectum, or between the number of bacteria and hormonal levels. Neither could any association between the presence of rectal lactobacilli and hormonal levels be found. Lactobacillus crispatus was more prevalent in the vaginal flora of fertile women, whereas the Lactobacillus flora of rectum did not correlate to the vaginal flora nor to hormonal levels.


A Ufd2/D4Cole1e chimeric protein and overexpression of Rbp7 in the slow Wallerian degeneration (WldS) mouse.
Exons of three genes were identified within the 85-kilobase tandem triplication unit of the slow Wallerian degeneration mutant mouse, C57BL/Wld(S). Ubiquitin fusion degradation protein 2 (Ufd2) and a previously undescribed gene, D4Cole1e, span the proximal and distal boundaries of the repeat unit, respectively. They have the same chromosomal orientation and form a chimeric gene when brought together at the boundaries between adjacent repeat units in Wld(S). The chimeric mRNA is abundantly expressed in the nervous system and encodes an in-frame fusion protein consisting of the N-terminal 70 amino acids of Ufd2, the C-terminal 302 amino acids of D4Cole1e, and an aspartic acid formed at the junction. Antisera raised against synthetic peptides detect the expected 43-kDa protein specifically in Wld(S) brain. This expression pattern, together with the previously established role of ubiquitination in axon degeneration, makes the chimeric gene a promising candidate for Wld. The third gene altered by the triplication, Rbp7, is a novel member of the cellular retinoid-binding protein family and is highly expressed in white adipose tissue and mammary gland. The whole gene lies within the repeat unit leading to overexpression of the normal transcript in Wld(S) mice. However, it is undetectable on Northern blots of Wld(S) brain and seems unlikely to be the Wld gene. These data reveal both a candidate gene for Wld and the potential of the Wld(S) mutant for studies of ubiquitin and retinoid metabolism.


Prebiotic effects of inulin and oligofructose.
Prebiotics are non-digestible food ingredients that target certain components within the microbiota of the human large intestine. Efficient prebiotics need to have a specific fermentation therein and thereby have the ability to alter the faecal microflora composition towards a more 'beneficial' community structure. This should occur by the stimulation of benign or potentially health promoting genera but not the harmful groups. Because of their positive attributes bifidobacteria and lactobacilli are the most frequent target organisms. Both inulin and oligofructose have been demonstrated to be effective prebiotics. This has been shown through both in vitro and in vivo assessments in different laboratories. Because of their recognised prebiotic properties, principally the selective stimulation of colonic bifidobacteria, both inulin and oligofructose are increasingly used in new food product developments. Examples include drinks, yoghurts, biscuits and table spreads. Because of the recognised inhibitory effects that bifidobacteria can exert against gut pathogens, one of the most important aspects of prebiotic ingestion is fortification of the gut flora to resist acute infections.


Neuropsychiatric symptoms in untreated Parkinson's disease.
Neuropsychiatric and cognitive symptoms are common in Parkinson's disease (PD) and may precede and exceed motor symptoms as major factors impacting disease course and quality of life. Neuropsychiatric symptoms (NPS) in PD are various and are attributed to pathologic changes within multiple brain regions, to psychological stress, and to adverse effects of dopamine replacement therapy. Sleep disorders and mood symptoms such as apathy, depression, and anxiety may antedate the development of motor symptoms by years, while other NPS such as impulse control disorders, psychosis, and cognitive impairment are more common in later stages of the disease. Few studies report on NPS in the early, untreated phase of PD. We reviewed the current literature on NPS in PD with a focus on the early, drug-naive stages of PD. Among these early disease stages, premotor and early motor phases were separately addressed in our review, highlighting the underlying pathophysiological mechanisms as well as epidemiological characteristics, clinical features, risk factors, and available techniques of clinical assessment.


Maternal consumption of fish oil programs reduced adiposity in broiler chicks.
Maternal intake of eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (22:6 n-3) has been associated with reduced adiposity in children, suggesting the possibility to program adipose development through dietary fatty acids before birth. This study determined if enriching the maternal diet in fish oil, the primary source of EPA and DHA, affected adipose development in offspring. Broiler chickens were used because they are obesity-prone, and because fatty acids provided to the embryo can be manipulated through the hen diet. Hens were fed diets supplemented (2.8% wt:wt) with corn oil (CO; n-6) or fish oil (FO; n-3) for 28 d. Chicks from both maternal diet groups were fed the same diet after hatch. Maternal FO consumption enriched chick adipose tissue in EPA and DHA and reduced adiposity by promoting more, but smaller, adipocytes. This adipocyte profile was paralleled by upregulated expression of the adipogenic regulator PPARG and its co-activator PPARGC1B, and reduced expression of LPL. Proteomics identified 95 differentially abundant proteins between FO and CO adipose tissue, including components of glucose metabolism, lipid droplet trafficking, and cytoskeletal organization. These results demonstrate that the maternal dietary fatty acid profile programs offspring adipose development.


Weak inhibitors protect cholinesterases from stronger inhibitors (dichlorvos): in vitro effect of tiapride.
Metoclopramide is a benzamide dopamine receptor antagonist and serotonine receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition, metoclopramide is a weak and reversible inhibitor of cholinesterases. The authors have previously shown that metoclopramide has a cholinesterase protective effect against inhibition by organophosphates (OPs). The putative mode of protective action of metoclopramide is, when administered in excess, competion for the active site of the enzyme with the more potent OP. In the present paper the authors present their results using another benzamide with weak cholinesterase inhibitory properties, tiapride (TIA). The purpose of the study was to quantify in vitro the extent of TIA-conferred protection, using dichlorvos (dichlorovinyl dimethyl phosphate; DDVP) as an inhibitor. DDVP is a moderately toxic (LD50 in rats in the milligram range), non-neuropathic OP. The substance is responsible for a large number of accidental or suicidal exposures. Red blood cell (RBC) acetylcholinesterase (AChE) activities in whole blood and butyrylcholinesterase (BChE) activities in human plasma were measured photometrically in the presence of different DDVP and TIA concentrations and IC50 was calculated. Determinations were repeated in the presence of increasing TIA concentrations. The IC50 of DDVP increases with the TIA concentration in a linear manner. The protective effect of TIA on cholinesterase could be of practical relevance in the treatment of OP poisoning. The authors conclude that in vivo testing of TIA as an OP protective agent is warranted.


Catalytic supramolecular self-assembled peptide nanostructures for ester hydrolysis.
Essential amino acids in catalytic sites of native enzymes are important in nature inspired catalyst designs. Active sites of enzymes contain the coordinated assembly of multiple amino acids, and catalytic action is generated by the dynamic interactions among multiple residues. However, catalysis studies are limited by the complex and dynamic structure of the enzyme; and it is difficult to exclusively attribute a given function to a specific residue. Minimalistic approaches involving artificial catalytic sites are promising for the investigation of the enzyme function in the absence of non-essential protein components, and self-assembling peptide nanostructures are especially advantageous in this context. Here we demonstrate the design and characterization of an enzyme-mimetic catalytic nanosystem presenting essential residues (Ser, His, Asp). The function of each residue and its combinations on the nanostructures in hydrolysis reaction was studied. The catalytic self-assembled nanostructures were used for efficient ester hydrolysis such as a model substrate (pNPA) and a natural substrate (acetylcholine) highlighting the key role of self-assembly in catalytic domain formation to test the efficiency of the de novo designed catalyst as a catalytic triad model.


A comparative study of antibacterial and anti-inflammatory effects of mouthrinse containing tea tree oil.
The study evaluated the antibacterial and anti-inflammatory efficacy, domiciliary oral hygiene, of a mouthrinse containing Tea Tree Oil (TTO) comparing it with two mouthrinses containing chlorhexidine 0,12% respectively and essential oils, and a placebo. A pilot study, randomized 4 × 4, controlled, cross-over, double-blind. 16 subjects with gingivitis (7 males and 9 females) aged 21-37 years, were randomly divided into four groups based on mouthwash that had to be used for domiciliary oral hygiene: mouthwash with essential oils, mouthwash with chlorhexidine 0,12 %, mouthwash containig tea tree oil and mouthwash placebo. Clinical evaluation was performed by: Full Mouth Plaque Score (FMPS), Full Mouth Bleeding Score (FMBS), Gingival Index (GI), discolorations, language examination and alteration of taste. The data were recorded before and 2 weeks after treatment. Statistical analysis shows that treatments with tea tree oil, essential oils and chlorhexidine are effective. Comparing treatments should be noted that the tea tree oil gives a greater improvement in the GI and FMBS, while it is the least effective in the control of bacterial plaque. Although further studies are needed, the anti-inflammatory properties of the mouthwash made from TTO would seem to be a valuable non-toxic adjunct in the management of gingivitis.


Comparison of age at natural menopause in BRCA1/2 mutation carriers with a non-clinic-based sample of women in northern California.
Germline mutations in BRCA1 and BRCA2 (BRCA1/2) are related to an increased lifetime risk of developing breast and ovarian cancer. Although risk-reducing salpingo-oophorectomy reduces the risk of both cancers, loss of fertility is a major concern. A recent study suggested an association between BRCA1 mutation and occult primary ovarian insufficiency. The objective of the current study was to determine whether BRCA1/2 mutation carriers have an earlier onset of natural menopause compared with unaffected women. White carriers of the BRCA1/2 gene (n = 382) were identified within the Breast Cancer Risk Program Registry at the University of California at San Francisco and compared with non-clinic-based white women in northern California (n = 765). The 2 groups were compared with regard to median age at the time of natural menopause before and after adjustment for known risk factors, and the role of smoking within each group was examined using the Kaplan-Meier approach for unadjusted analyses and Cox proportional hazards regression analyses for adjusted analyses. The median age at the time of natural menopause in the BRCA1/2 carriers was significantly younger than among the unaffected sample (50 years vs 53 years; P < .001). The unadjusted hazard ratio for natural menopause when comparing BRCA1/2 carriers with unaffected women was 4.06 (95% confidence interval, 3.03-5.45) and was 3.98 (95% confidence interval, 2.87-5.53) after adjusting for smoking, parity, and oral contraceptive use. For BRCA1/2 carriers who were current heavy smokers (smoking ≥ 20 cigarettes/day), the median age at natural menopause was 46 years versus 49 years for nonsmokers (P = .027). The BRCA1/2 mutation was associated with a significantly earlier age at natural menopause, and heavy smoking compounded this risk. Because the relationship between menopause and the end of natural fertility is considered to be fixed, these findings suggest the risk of earlier infertility among BRCA1/2 carriers.


Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice.
The aging process is associated with the development of several chronic diseases. White adipose tissue (WAT) may play a central role in age-related disease onset and progression due to declines in adipogenesis with advancing age. Recent reports indicate that the accumulation of senescent progenitor cells may be involved in age-related WAT dysfunction. Growth hormone (GH) action has profound effects on adiposity and metabolism and is known to influence lifespan. In the present study we tested the hypothesis that GH activity would predict age-related WAT dysfunction and accumulation of senescent cells. We found that long-lived GH-deficient and -resistant mice have reduced age-related lipid redistribution. Primary preadipocytes from GH-resistant mice also were found to have greater differentiation capacity at 20 months of age when compared to controls. GH activity was also found to be positively associated with senescent cell accumulation in WAT. Our results demonstrate an association between GH activity, age-related WAT dysfunction, and WAT senescent cell accumulation in mice. Further studies are needed to determine if GH is directly inducing cellular senescence in WAT or if GH actions on other target organs or alternative downstream alterations in insulin-like growth factor-1, insulin or glucose levels are responsible.


Relationship Between Abortion at First Pregnancy and Live Births by Young Adulthood: A Population-Based Study Among Mexican Women.
To identify factors associated with having an abortion (spontaneous or induced) at the time of first pregnancy, and to test the association between abortion in the first pregnancy and the number of live births among young women 20-24 years of age. Cross-sectional study. We used a nationally representative survey of Mexican women 20-24 years of age with data at time of survey and retrospective measures of exposures in adolescence. We include 1913 women who reported ever having a pregnancy. Our outcomes were history of abortion (spontaneous or induced) and number of live births by 20-24 years of age. We used multivariable logistic regression models to estimate the association between sociodemographic factors at the time of pregnancy and abortion history, and between abortion history and number of live births. Among women 20-24 years of age who ever had a pregnancy, 15.5% reported an abortion in the first pregnancy, and 84.4% never had an abortion. Among women who had an abortion in the first pregnancy, 62.3% did not report any live birth by age 20-24 years. Young women living with their parents (adjusted odds ratio [AOR] = 1.87; confidence interval [CI] = 1.16-3.02) or with a partner with a higher educational level (AOR = 4.64; CI = 1.05-20.44) had greater odds of having an abortion in the first pregnancy. Compared with women who never had an abortion, women who reported an abortion in the first pregnancy had lower odds (AOR = 0.02; CI = 0.01-0.03) of having 1 or more children by the age of 20-24 years. Young women who reported abortion in the first pregnancy had fewer live births at ages 20-24 years compared to women with no history of abortion.


Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy: A Pragmatic Randomized Clinical Trial Comparing a Viscoelastic Assay to Conventional Coagulation Assays.
Massive transfusion protocols (MTPs) have become standard of care in the management of bleeding injured patients, yet strategies to guide them vary widely. We conducted a pragmatic, randomized clinical trial (RCT) to test the hypothesis that an MTP goal directed by the viscoelastic assay thrombelastography (TEG) improves survival compared with an MTP guided by conventional coagulation assays (CCA). This RCT enrolled injured patients from an academic level-1 trauma center meeting criteria for MTP activation. Upon MTP activation, patients were randomized to be managed either by an MTP goal directed by TEG or by CCA (ie, international normalized ratio, fibrinogen, platelet count). Primary outcome was 28-day survival. One hundred eleven patients were included in an intent-to-treat analysis (TEG = 56, CCA = 55). Survival in the TEG group was significantly higher than the CCA group (log-rank P = 0.032, Wilcoxon P = 0.027); 20 deaths in the CCA group (36.4%) compared with 11 in the TEG group (19.6%) (P = 0.049). Most deaths occurred within the first 6 hours from arrival (21.8% CCA group vs 7.1% TEG group) (P = 0.032). CCA patients required similar number of red blood cell units as the TEG patients [CCA: 5.0 (2-11), TEG: 4.5 (2-8)] (P = 0.317), but more plasma units [CCA: 2.0 (0-4), TEG: 0.0 (0-3)] (P = 0.022), and more platelets units [CCA: 0.0 (0-1), TEG: 0.0 (0-0)] (P = 0.041) in the first 2 hours of resuscitation. Utilization of a goal-directed, TEG-guided MTP to resuscitate severely injured patients improves survival compared with an MTP guided by CCA and utilizes less plasma and platelet transfusions during the early phase of resuscitation.


Herbal medicines: challenges in the modern world. Part 4. Canada and United States.
Similar to other nations North American people used herbs for thousands of years to treat diseases and purify their spirits. By the middle of the 1900s, evidence-based conventional medicine received wide acceptance in Canada and the United States (US). Nowadays, people are going back to their roots and actively using herbal medicines (HMs) and natural health products (NHPs). Areas covered: This article is focusing on use and regulation of the HMs and NHPs in Canada and the US, raises concerns regarding HM and NHP safety and efficacy, offers suggestions on how to overcome these problems. Materials available from legislative and governmental websites, PubMed and news media were used. Expert commentary: Use of HMs, especially dietary supplements is widespread among adults in Canada and US. HMs and NHPs are regulated in both countries, but minimum criteria for product approval and post-market surveillance have been set. Concerns of quality, contamination, adulteration, and efficacy in are of central importance in the discussion of HMs and NHPs. Detailed product description and research are of vital importance to ensure safety and efficacy of these products. Additionally, 'herbal' education of healthcare providers and patients is needed to guarantee further successful integration of HM and conventional medicines.


[Tooth and jaw injuries following violence--diagnosis and treatment in emergency department].
Research over the last decade has confirmed that facial injuries caused by violence occur most frequently among young males, often under the influence of alcohol, and less frequently in women and children following domestic violence. Evidence of injuries may be used in court or in claims for compensation, and must be carefully documented. Facial asymmetry, deviation of the mandible in opening, altered occlusion and/or abrasions under the chin may be indications of jaw fractures; such patients are referred to oral surgery units for further treatment. Lacerations and ulceration in the oral mucous membrane should be treated as skin wounds. A fractured tooth should be referred to a general dental practitioner. Luxated teeth should be carefully replaced and immediately referred to a dentist for fixation. Completely avulsed teeth should immediately be replaced, preferably at the site of the accident, or immediately upon arrival at the clinic. Prompt referral to a dental practitioner for follow-up treatment is essential for the success of replantations. Additional documentation of the injury may be provided by photographs, radiographs and drawings. The letter of referral to the dentist should contain the following information: data on the patient, the circumstances, clinical findings, treatment performed and prescriptions given, together with advice given to the patient.


Comparative genomics and host resistance against infectious diseases.
The large size and complexity of the human genome have limited the identification and functional characterization of components of the innate immune system that play a critical role in front-line defense against invading microorganisms. However, advances in genome analysis (including the development of comprehensive sets of informative genetic markers, improved physical mapping methods, and novel techniques for transcript identification) have reduced the obstacles to discovery of novel host resistance genes. Study of the genomic organization and content of widely divergent vertebrate species has shown a remarkable degree of evolutionary conservation and enables meaningful cross-species comparison and analysis of newly discovered genes. Application of comparative genomics to host resistance will rapidly expand our understanding of human immune defense by facilitating the translation of knowledge acquired through the study of model organisms. We review the rationale and resources for comparative genomic analysis and describe three examples of host resistance genes successfully identified by this approach.


Successful Deep Inferior Epigastric Perforator Flap Harvest despite Preoperative Therapeutic Subcutaneous Heparin Administration into the Abdominal Pannus.
Abdominal free flaps for microsurgical breast reconstruction are most commonly harvested based on the deep inferior epigastric vessels that supply skin and fat via perforators through the rectus muscle and sheath. Intact perforator anatomy and connections are vital for subsequent optimal flap perfusion and avoidance of necrosis, be it partial or total. The intraflap vessels are delicate and easily damaged and it is generally advised that patients should avoid heparin injection into the abdominal pannus preoperatively as this may compromise the vascular perforators through direct needle laceration, pressure from bruising, haematoma formation, or perforator thrombosis secondary to external compression. We report three cases of successful deep inferior epigastric perforator (DIEP) flap harvest despite patients injecting therapeutic doses of low molecular weight heparin into their abdomens for thrombosed central venous lines (portacaths™) used for administering primary chemotherapy in breast cancer.


Connectome-based predictive modeling of fluid intelligence: evidence for a global system of functionally integrated brain networks.
Cognitive neuroscience continues to advance our understanding of the neural foundations of human intelligence, with significant progress elucidating the role of the frontoparietal network in cognitive control mechanisms for flexible, intelligent behavior. Recent evidence in network neuroscience further suggests that this finding may represent the tip of the iceberg and that fluid intelligence may depend on the collective interaction of multiple brain networks. However, the global brain mechanisms underlying fluid intelligence and the nature of multi-network interactions remain to be well established. We therefore conducted a large-scale Connectome-based Predictive Modeling study, administering resting-state fMRI to 159 healthy college students and examining the contributions of seven intrinsic connectivity networks to the prediction of fluid intelligence, as measured by a state-of-the-art cognitive task (the Bochum Matrices Test). Specifically, we aimed to: (i) identify whether fluid intelligence relies on a primary brain network or instead engages multiple brain networks; and (ii) elucidate the nature of brain network interactions by assessing network allegiance (within- versus between-network connections) and network topology (strong versus weak connections) in the prediction of fluid intelligence. Our results demonstrate that whole-brain predictive models account for a large and significant proportion of variance in fluid intelligence (18%) and illustrate that the contribution of individual networks is relatively modest by comparison. In addition, we provide novel evidence that the global architecture of fluid intelligence prioritizes between-network connections and flexibility through weak ties. Our findings support a network neuroscience approach to understanding the collective role of brain networks in fluid intelligence and elucidate the system-wide network mechanisms from which flexible, adaptive behavior is constructed.


Demonstration and structural comparison of receptors for insulin-like growth factor-I and -II (IGF-I and -II) in brain and blood-brain barrier.
Specific receptors for insulin-like growth factors (IGF) I and II on microvessel-free rat brain cell membranes (RBCM) and in the microvessels that constitute the blood-brain barrier (BBB) were identified and characterized by means of affinity cross-linking techniques and specific anti-receptor antibodies. Two different models of BBB were examined: isolated rat brain capillaries and cultured bovine brain microvessel endothelial cells. Cross-linking with 125-I-IGF-I, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), revealed an alpha subunit of apparent Mr = 138,000 in both BBB preparations, compared to 120,000 in RBCM. Cross-linking was inhibited by unlabeled IGF and insulin, but not by antibody directed against the IGF-II receptor. When 125-I-IGF-II was cross-linked, followed by SDS-PAGE under reducing conditions, a major band of apparent Mr = 250,000 was identified in RBCM and both BBB preparations. This band, which migrated with an approximately equivalent Mr in both brain and BBB membranes, was inhibited by unlabeled IGF and by antibody specific for the IGF-II receptor. Thus, both rat and bovine brain microvessels possess classical Type I and II IGF receptors. While the alpha subunit of the Type I receptor of brain is smaller than that of the BBB, the Type II receptor of brain and BBB appear to be structurally and immunologically identical.


Modelling the dissolution of non-aqueous phase liquid blobs in sphere packings.
Pore-scale modelling is appealing for investigating and obtaining macroscale constitutive equations for multiphase porous medium systems, because this approach bridges the macroscopic and microscopic scales. In this study, we develop a method to simulate and study the dissolution of non-aqueous phase liquid (NAPL) blobs; accurately quantifying NAPL mass transfer is crucial for modelling decontamination studies faithfully. We simulate a random packing of spheres and a residual NAPL distribution by matching macroscopic morphological descriptors of an experimental NAPL distribution; then we simulate single-phase flow by using a lattice-Boltzmann approach. Finally we numerically solve the advection-diffusion equation in the pore space to simulate mass transfer and transport of the dissolved components. Based upon different simulation results, we evaluate the sensitivity of the mass transfer coefficient with respect to two non-dimensional parameters and compare the simulation results to existing empirical relationships.


Functional interconnectivity between the globus pallidus and the subthalamic nucleus in the mouse brain slice.
In accordance with its central role in basal ganglia circuitry, changes in the rate of action potential firing and pattern of activity in the globus pallidus (GP)-subthalamic nucleus (STN) network are apparent in movement disorders. In this study we have developed a mouse brain slice preparation that maintains the functional connectivity between the GP and STN in order to assess its role in shaping and modulating bursting activity promoted by pharmacological manipulations. Fibre-tract tracing studies indicated that a parasagittal slice cut 20 deg to the midline best preserved connectivity between the GP and the STN. IPSCs and EPSCs elicited by electrical stimulation confirmed connectivity from GP to STN in 44/59 slices and from STN to GP in 22/33 slices, respectively. In control slices, 74/76 (97%) of STN cells fired tonically at a rate of 10.3 +/- 1.3 Hz. This rate and pattern of single spiking activity was unaffected by bath application of the GABA(A) antagonist picrotoxin (50 microM, n = 9) or the glutamate receptor antagonist (6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) 10 microM, n = 8). Bursting activity in STN neurones could be induced pharmacologically by application of NMDA alone (20 microm, 3/18 cells, 17%) but was more robust if NMDA was applied in conjunction with apamin (20-100 nM, 34/77 cells, 44%). Once again, neither picrotoxin (50 microM, n = 5) nor CNQX (10 microM, n = 5) had any effect on the frequency or pattern of the STN neurone activity while paired STN and GP recordings of tonic and bursting activity show no evidence of coherent activity. Thus, in a mouse brain slice preparation where functional GP-STN connectivity is preserved, no regenerative synaptically mediated activity indicative of a dynamic network is evident, either in the resting state or when neuronal bursting in both the GP and STN is generated by application of NMDA/apamin. This difference from the brain in Parkinson's disease may be attributed either to insufficient preservation of cortico-striato-pallidal or cortico-subthalamic circuitry, and/or an essential requirement for adaptive changes resulting from dopamine depletion for the expression of network activity within this tissue complex.


Epigenetic regulation of androgen receptor signaling in prostate cancer.
Prostate cancer is the most common cancer in men in the United States, and it is the second leading cause of cancer-related death in American men. The Androgen receptor (AR), a nuclear hormone and transcription factor, is the most therapeutically relevant target in this disease. While most efforts in the clinic are still directed at lowering levels of androgens that activate AR, resistance to androgen deprivation eventually develops, and most prostate cancer deaths are attributable to this castration-resistant form of this disease. Recent work has shed light on the importance of epigenetic events including facilitation of AR signaling by histone-modifying enzymes and also on the role that enzymes such as HDAC6 play in stabilizing AR in prostate cancer cells. Herein, we summarize recent findings on the role of epigenetic enzymes in AR signaling and highlight examples on how interdiction of critical epigenetic enzymes may attenuate AR action in prostate cancer.


Human Thalamic Somatosensory Nucleus (Ventral Caudal, Vc) as a Locus for Stimulation by INPUTS from Tactile, Noxious and Thermal Sensors on an Active Prosthesis.
The forebrain somatic sensory locus for input from sensors on the surface of an active prosthesis is an important component of the Brain Machine Interface. We now review the neuronal responses to controlled cutaneous stimuli and the sensations produced by Threshold Stimulation at Microampere current levels (TMIS) in such a locus, the human thalamic Ventral Caudal nucleus (Vc). The responses of these neurons to tactile stimuli mirror those for the corresponding class of tactile mechanoreceptor fiber in the peripheral nerve, and TMIS can evoke sensations like those produced by the stimuli that optimally activate each class. These neuronal responses show a somatotopic arrangement from lateral to medial in the sequence: leg, arm, face and intraoral structures. TMIS evoked sensations show a much more detailed organization into anterior posteriorly oriented rods, approximately 300 microns diameter, that represent smaller parts of the body, such as parts of individual digits. Neurons responding to painful and thermal stimuli are most dense around the posterior inferior border of Vc, and TMIS evoked pain sensations occur in one of two patterns: (i) pain evoked regardless of the frequency or number of spikes in a burst of TMIS; and (ii) the description and intensity of the sensation changes with increasing frequencies and numbers. In patients with major injuries leading to loss of somatic sensory input, TMIS often evokes sensations in the representation of parts of the body with loss of sensory input, e.g., the phantom after amputation. Some patients with these injuries have ongoing pain and pain evoked by TMIS of the representation in those parts of the body. Therefore, thalamic TMIS may produce useful patterned somatotopic feedback to the CNS from sensors on an active prosthesis that is sometimes complicated by TMIS evoked pain in the representation of those parts of the body.


Sibilant production in Hebrew-speaking adults: Apical versus laminal.
The Hebrew IPA charts describe the sibilants /s, z/ as 'alveolar fricatives', where the place of articulation on the palate is the alveolar ridge. The point of constriction on the tongue is not defined - apical (tip) or laminal (blade). Usually, speech and language pathologists (SLPs) use the apical placement in Hebrew articulation therapy. Some researchers and SLPs suggested that acceptable /s, z/ could be also produced with the laminal placement (i.e. the tip of the tongue approximating the lower incisors). The present study focused at the clinical level, attempting to determine the prevalence of these alternative points of constriction on the tongue for /s/ and /z/ in three different samples of Hebrew-speaking young adults (total n = 242), with typical articulation. Around 60% of the participants reported using the laminal position, regardless of several speaker-related variables (e.g. tongue-thrust swallowing, gender). Laminal production was more common in /s/ (than /z/), coda (than onset) position of the sibilant, mono- (than di-) syllabic words, and with non-alveolar (than alveolar) adjacent consonants. Experiment 3 revealed no acoustical differences between apical and laminal productions of /s/ and of /z/. From a clinical perspective, we wish to raise the awareness of SLPs to the prevalence of the two placements when treating Hebrew speakers, noting that tongue placements were highly correlated across sibilants. Finally, we recommend adopting a client-centred practice, where tongue placement is matched to the client. We further recommend selecting targets for intervention based on our findings, and separating between different prosodic positions in treatment.


Evaluation of synthetic composite tibias for fracture testing using impact loads.
Composite synthetic bones are a commercially available substitute for cadaveric specimens, and they have previously been validated to replicate natural bone under quasistatic, non-destructive testing. Synthetic tibias could be used to analyse injury risk to the lower leg during impact events, but their failure mode must be validated by way of comparative tests to human bone. Synthetic tibias were instrumented with strain gauges and subjected to axial impact loading. Two different projectile masses were used for the tests, and the effects of force, momentum, and energy on failure were compared with previous cadaveric data. The composite tibias failed at forces between 37-45 per cent of those from cadavers, and failed via cortical delamination in combination with fracture. A Weibull analysis generated a survivability curve based on axial force at failure, and was shown to be lower than previous cadaveric curves. Failure was dependent on both the momentum and energy applied. Strain distributions through the synthetic tibias were significantly different from those of cadavers. The convex distal articular surface of the synthetic bones may partially account for the lower fracture tolerance. As a result of the many differences in response, these synthetic tibias are not recommended for use in impact fracture studies.


Covert orienting of visual spatial attention in attention deficit hyperactivity disorder: does comorbidity make a difference?
Attentional performance in children with attention deficit hyperactivity disorder (ADHD) with and without comorbid disorders was examined using the Covert Orienting of Visuospatial Attention Task (COVAT) and the Continuous Performance Task (CPT). The relationship between these two tasks was also examined. The results showed no overall differences on the attention tasks between children with ADHD alone and those with ADHD plus other disorders. Compared to non-ADHD control children, children with ADHD showed a deficit in the disengage operation of covert visuospatial attention, suggesting a difficulty in the endogenous mode of orienting. The ADHD children also showed a general performance deficit on the CPT. Although there was a general slowing on both attention tasks in the ADHD group, there was no relationship between invalid cue effect sizes on the COVAT and the CPT measures. These results indicate that these two attention tasks may be tapping both similar and independent underlying cognitive processes in ADHD.


Effect of anodal and cathodal microamperage direct current electrical stimulation on injury potential and wound size in guinea pigs.
Injury potential may have a regulatory role in the wound healing process, and exogenous electrical stimulation (ES) may mimic natural endogenous bioelectric current that can improve wound healing. Until now, the influence of externally applied ES on injury potential has not been demonstrated during the healing of acute wounds. Thirty-nine male guinea pigs were randomly divided into a control group (sham treatment) and two experimental groups: anodal and cathodal direct current (DC). A 2.5 cm-long full-thickness skin incision was made on each animal's dorsal region. Differential skin surface potential was measured before and immediately after the injury and also through day 21 of the healing period; wound surface area (WSA) was also measured throughout the 21-day healing period. Immediately after injury, wound potential significantly increased in all three groups, reaching a maximum on day 1 for the control and cathodal groups and day 3 for the anodal group (p < 0.05), then decreasing through the healing period. Wound potential returned to preinjury levels by the end of the healing period in the anodal group only. By days 19 and 21, wound potential had decreased more for the anodal group than the control group (p < 0.05). By day 15 for the anodal group and day 17 for the cathodal group, WSA had decreased more compared with the control group (p < 0.05). Anodal microamperage DC ES is appropriate for improving the healing of acute skin wounds because it causes both the wound surface to close and the wound potential to return to preinjury levels faster.


Depressive Symptoms and Suicidal Ideation Among Symptomatic Patients With a History of Lyme Disease vs Two Comparison Groups.
Depression has been reported in 8-45% of patients with posttreatment Lyme symptoms (PTLS), but little is known about suicidal ideation in these patients. Depression and suicidal ideation were assessed using the Beck Depression Inventory (BDI-II). Scores from the PTLS group (n = 81) were compared to those from 2 other groups: HIV+ patients being treated for fatigue (n = 70), and a nonpatient comparison group (NPCG; n = 44). ANOVA and t-tests were used to compare groups; logistic regression was used to identify the strongest correlates of suicidal ideation. Mean BDI-II scores fell in the mildly depressed range for PTLS and HIV+ patients, with both groups having higher depression scores than the NPCG. Suicidal ideation was reported by 19.8% of the PTLS patients and 27.1% of the HIV+ patients, a nonsignificant difference. Among those with mild or no depression, suicidal ideation was uncommon (6.5% PTLS and 11.9% HIV+). Among the patients with moderate-to-severe depression, suicidal ideation was more common (63.2% of 19 PTLS and 50% of 28 HIV+); among these, 2 with PTLS and 1 with HIV+ expressed suicidal intent. Further, 4.5% (n = 2) of the NPCG had suicidal ideation, each had scores in the moderate-to-severe depression range. Higher scores on the cognitive symptoms subscale of the BDI-II predicted greater likelihood of suicidal ideation across patient groups. As expected, suicidal ideation is increased among patients who are depressed. The fact that 1 in 5 patients with PTLS reported suicidal ideation highlights the importance of screening for depression and suicidality to optimize patient care.


Pertussis toxin-induced ADP ribosylation of inhibitor G proteins alters vagal control of heart rate in vivo.
Prior studies have shown that in vivo systemic administration of pertussis toxin in conscious dogs catalyzes ADP ribosylation of Gi and G(o) proteins, which attenuates intracellular transduction of muscarinic receptor activation. We tested the hypothesis that this impairment may result in the alteration of the following indexes of cardiac vagal activity: baroreflex sensitivity and heart rate variability. Heart rates during submaximal exercise were also determined. These variables were measured in eight conscious dogs before and 72 hr after pertussis toxin administration. Pertussis toxin significantly reduced (P < 0.001) baroreflex sensitivity (from 18.7 +/- 2.6 to 6.8 +/- 1.4 ms/mmHg), the SD of the mean R-R intervals (from 176 +/- 17 to 61 +/- 7 ms), the mean R-R interval (from 742 +/- 32 to 527 +/- 29 ms), and the coefficient of variance [from 235 +/- 15 to 114 +/- 1 (x 1,000)]. The heart rate response to graded submaximal exercise after pertussis toxin was higher (P < 0.001) at each exercise level. In in vitro assay, cardiac tissue samples from pertussis toxin-treated dogs incorporated 10-fold less ADP ribose than what has been described previously. These data prove that the in vivo action of pertussis toxin on cardiac inhibitory G proteins has direct consequences on end-organ cardiac responses to vagal activity. This study quantifies the physiological consequences of pertussis toxin-induced impairment of inhibitory G proteins in conscious animals.


Localization techniques for guided surgical excision of non-palpable breast lesions.
Breast cancer is the most common form of cancer and the second leading cause of death amongst women in Europe. Amongst five invasive cancers per 1000 women detected in screening, 2.7 were < 15 mm in diameter; and others reported that over one third of excised breast lesions were clinically occult. The challenge is to accurately locate small non-palpable lesions intraoperatively for optimal therapeutic outcome. A secondary important goal is to remove the smallest amount possible of healthy glandular tissue for optimal cosmesis. Currently the most widely adopted approach (80% in one survey) in guided breast-conserving surgery for excising non-palpable breast lesions is wire-guided localization (WGL). With the clinical setting shifting towards earlier non-palpable breast lesions being detected through screening, we investigated whether the current standard in assisting surgical excision of these lesions, WGL, yields the best therapeutic outcome for women with breast cancer. To assess the therapeutic outcomes of any new form of guided surgical intervention for non-palpable breast lesions against wire-guided localization, the current gold standard. We searched the Cochrane Breast Cancer Group's (CBCG) Specialized Register, MEDLINE (via PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal from the earliest available date up to 30 March 2015. We also handsearched recent conference proceedings and sought information from experts in the field. Two review authors, BC and RJ, independently screened by title and abstract the studies we had identified through the search strategy; when this was inconclusive, they examined the full-text article for inclusion. We resolved any discrepancies regarding eligibility by discussion with a third review author, RA. Three review authors, BC, JW, and RJ, independently extracted data using a standardized data sheet. We performed all analyses using Review Manager (RevMan) or the R meta package, and in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. We reported results via a graphical assessment using forest plots showing the study estimates. We considered and discussed additional subgroup and sensitivity analyses. We identified 11 randomized controlled trials (RCTs) that met the inclusion criteria of this Cochrane review and included eight trials in the meta-analyses. Six RCTs compared radioguided occult lesion localization (ROLL) versus WGL, and two RCTs compared radioactive iodine ((125)I) seed localization (RSL) versus WGL. Of the three remaining trials, one RCT compared cryo-assisted techniques (CAL) versus WGL, one compared intraoperative ultrasound-guided lumpectomy (IOUS) versus WGL, and one compared modified ROLL technique in combination with methylene dye (RCML) versus WGL. Of the trials we included in the meta-analysis, there were a total of 1273 participants with non-palpable breast lesions (627 participants (WGL); 443 participants (ROLL); and 203 participants (RSL)). The participant population varied considerably between included trials, which included participants with both non-palpable benign and malignant lesions, and varied in defining clear margins. The included trials did not report any long-term outcomes.In general, the outcomes of WGL, ROLL and RSL were comparable.ROLL demonstrated favourable results in successful localization (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.16 to 2.28; 869 participants; six trials), positive excision margins (RR 0.74, 95% CI 0.42 to 1.29; 517 participants; five trials), and re-operation rates (RR 0.51, 95% CI 0.21 to 1.23; 583 participants; four trials) versus WGL, but none were statistically significant. WGL was significantly superior to RSL in successfully localizing non-palpable lesions (RR 3.85, 95% CI 1.21 to 12.19; 402 participants; two trials). However, for successful excision, ROLL and RSL have comparable outcomes versus WGL (ROLL versus WGL: RR 1.00, 95% CI 0.99 to 1.01; 871 participants; six trials; RSL versus WGL: RR 1.00, 95% CI 0.99 to 1.01; 402 participants; two trials). These findings were similar in that RSL demonstrated favourable results over WGL in positive tumour margins (RR 0.67, 95% CI 0.43 to 1.06; 366 participants; two trials), and re-operation rates (RR 0.80, 95% CI 0.48 to 1.32; 305 participants; one trial) but neither reached statistical significance. In contrast, WGL had fewer postoperative complications to both ROLL (RR 1.18, 95% CI 0.71 to 1.98; 642 participants; four trials) and RSL (RR 1.51, 95% CI 0.75 to 3.03; 305 participants; one trial), although this was also not statistically significant.The overall quality of evidence was good. The main risk of bias amongst included studies consisted of incomplete data sets, selective reporting, and allocation concealment. Interpretation and applicability of this meta-analysis was hindered by the mixed indication of diagnostic versus therapeutic purposes when undertaking WGL, ROLL, or RSL, leading to a high level of mixed pathology in numerous trials. Other limitations include underpowered studies, lack of data in standardized format for meta-analysis, lack of complete data amongst the trials, and absence of long-term data. Owing to a lack of trials in certain localization techniques, we could only draw conclusions about ROLL and RSL versus WGL. There is no clear evidence to support one guided technique for surgically excising a non-palpable breast lesion over another. Results from this Cochrane review support the continued use of WGL as a safe and tested technique that allows for flexibility in selected cases when faced with extensive microcalcification. ROLL and RSL could be offered to patients as a comparable replacement for WGL as they are equally reliable. Other techniques such as IOUS, RCML, and CAL are of academic interest, but recommendation for routine use in the clinical environment and oncological outcomes require further validation. The results of this Cochrane review also stress the need for more fully powered RCTs to evaluate the best technique according to the comprehensive criteria described, with a more consistent and standardized approach in outcome reporting.


An incidental finding of chronic salpingitis complications: Tubo-uterine fistula.
Pelvic inflammatory disease (PID) is an infection of the upper genital tract in women that can include endometritis, parametritis, salpingitis, oophoritis, tubo-ovarian abscess, and peritonitis. The spectrum of the disease ranges from subclinical and asymptomatic infection to severe, lifethreatening illness; squealae include chronic pelvic pain, ectopic pregnancy, and infertility. In this case we report an uncommon complication of pelvic inflammatory disease, a tubo-uterian fistula. Our case was diagnosed by laparoscopy incidentally during assessment of infertility.


Retention of in vitro and in vivo BMP-2 bioactivities in sustained delivery vehicles for bone tissue engineering.
In this study, we investigated the in vitro and in vivo biological activities of bone morphogenetic protein 2 (BMP-2) released from four sustained delivery vehicles for bone regeneration. BMP-2 was incorporated into (1) a gelatin hydrogel, (2) poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in a gelatin hydrogel, (3) microspheres embedded in a poly(propylene fumarate) (PPF) scaffold and (4) microspheres embedded in a PPF scaffold surrounded by a gelatin hydrogel. A fraction of the incorporated BMP-2 was radiolabeled with (125)I to determine its in vitro and in vivo release profiles. The release and bioactivity of BMP-2 were tested weekly over a period of 12 weeks in preosteoblast W20-17 cell line culture and in a rat subcutaneous implantation model. Outcome parameters for in vitro and in vivo bioactivities of the released BMP-2 were alkaline phosphatase (AP) induction and bone formation, respectively. The four implant types showed different in vitro release profiles over the 12-week period, which changed significantly upon implantation. The AP induction by BMP-2 released from gelatin implants showed a loss in bioactivity after 6 weeks in culture, while the BMP-2 released from the other implants continued to show bioactivity over the full 12-week period. Micro-CT and histological analysis of the delivery vehicles after 6 weeks of implantation showed significantly more bone in the microsphere/PPF scaffold composites (Implant 3, p<0.02). After 12 weeks, the amount of newly formed bone in the microsphere/PPF scaffolds remained significantly higher than that in the gelatin and microsphere/gelatin hydrogels (p<0.001), however, there was no statistical difference compared to the microsphere/PPF/gelatin composite. Overall, the results from this study show that BMP-2 could be incorporated into various bone tissue engineering composites for sustained release over a prolonged period of time with retention of bioactivity.


Contaminants of non-biological origin in foods from animals.
The authors provide an overview of non-biological contaminants in foods from animals. These contaminants comprise chemical and physical hazards which may be introduced during animal production, slaughter and processing or packaging. Emphasis in this paper is placed on those residues which are of most interest to Veterinary Services and for which Veterinary Services have responsibility, namely: residues of veterinary drugs, industrial chemicals, heavy metals and pesticides which may be introduced during animal production. The most contentious residues which occur in meat, milk and eggs are antibacterial drugs, hormonal growth promoters and certain pesticides, heavy metals and industrial chemicals. While rare incidents of human disease have been attributed to hazardous levels of these contaminants in milk and meat, residues of chemical contaminants in foods of animal origin are, in general, rarely detected at more than trace levels and consequently are not of major public health concern. Nevertheless, non-biological contaminants continue to be very important with respect to international trade and consumer confidence, and efforts to reduce the incidence of occurrence in foods is warranted. Furthermore, continued monitoring and periodic reassessment of risks posed by these contaminants is needed to detect or anticipate new problems so that appropriate action can be taken in the interests of public safety.


The impact of universal recycling on the evolution of economic diversity.
Based on von Neumann's model of an economy characterized by processes and goods, we add to that model a component representing capital equipment. We assume that the need for capital equipment by any process is proportional to the rate at which that process is running, and therefore an increase in rate requires that capital equipment be purchased, whereas a decrease in rate allows capital equipment to be sold. We thereby construct a continuous-time dynamical model, which we use to investigate the evolution of economic diversity under two price equilibrium scenarios: the first with non-negative prices and non-positive excess demands; the second with enforced market clearing and with prices allowed to be negative. The second scenario represents an economy in which recycling is required, so that excess supply cannot be discarded. We prove that at any time during the progression of the model economy, the solution to each of the two price equilibrium problems exists, and that non-uniqueness of the solution, if any, does not affect the development of the model economy. We compare matched model economies under the two scenarios by simulating their respective evolutions. In each case, the model economy experiences a process of selection and matures to a state of balanced growth, with a higher growth rate when excess supply is discarded, but with greater economic diversity with enforced recycling. The robustness of these qualitative results is demonstrated by repeated trials of simulations on matched pairs of model economies with different randomly chosen parameters.


[Immune system physiology].
Processes of interaction of immunocytes of different origin and with different cytokins, underlie the immune system mechanisms. The immune system structure, lymphocytes variety and properties, molecular basis of antigen recognition, were described. Dynamic structure of peripheral part of the immune system, immunocytes migration and re-circulation role in integration of lymphoid organs, were demonstrated. The molecular and cellular basis of the immune reaction and immune memory, were discussed.


Automated detection of foveal center in SD-OCT images using the saliency of retinal thickness maps.
To develop an automated method based on saliency map of the retinal thickness map to determine foveal center in spectral-domain optical coherence tomography (SD-OCT) images. This paper proposes an automatic method for the detection of the foveal center in SD-OCT images. Initially, a retinal thickness map is generated by considering the axial distance between the internal limiting membrane (ILM) and the Bruch's membrane (BM). Both the ILM and BM boundaries are automatically segmented by a known retinal segmentation technique. The macular foveal region is identified as a salient feature in the retinal thickness map, and segmented by the saliency detection method based on a human vision attention model. Finally, the foveal center is identified by searching for the lowest point from the determined macular fovea region. Experimental results in 39 scans from 35 healthy eyes and 58 scans from 29 eyes diagnosed with several stages of age-related macular degeneration (AMD), from mild or intermediate stages to severe dry or wet stages, demonstrated that the proposed method achieves good performance. The mean radial distance error of the automatically detected foveal center locations when compared to consensus manual determination established by repeated sessions from two expert readers was 52 ± 56 μm for the normal eyes and 73 ± 63 μm for AMD eyes. The proposed algorithm was more effective for detecting the foveal center automatically in SD-OCT images than the state-of-art methods.


Histamine synergistically promotes bFGF-induced angiogenesis by enhancing VEGF production via H1 receptor.
Histamine, a major mediator present in mast cells that is released into the extracellular milieu upon degranulation, is well known to possess a wide range of biological activities in several classic physiological and pathological processes. However, whether and how it participates in angiogenesis remains obscure. In the present study, we observed its direct and synergistic action with basic fibroblast growth factor (bFGF), an important inducer of angiogenesis, on in vitro angiogenesis models of endothelial cells. Data showed that histamine (0.1, 1, 10 µM) itself was absent of direct effects on the processes of angiogenesis, including the proliferation, migration, and tube formation of endothelial cells. Nevertheless, it could concentration-dependently enhance bFGF-induced angiogenesis as well as production of vascular endothelial growth factor (VEGF) from endothelial cells. The synergistic effect of histamine on VEGF production could be reversed by pretreatments with diphenhydramine (H1-receptor antagonist), SB203580 (selective p38 mitogen-activated protein kinase (MAPK) inhibitor) and L-NAME (nitric oxide synthase (NOS) inhibitor), but not with cimetidine (H2-receptor antagonist) and indomethacin (cyclooxygenase (COX) inhibitor). Moreover, histamine could augment bFGF-incuced phosphorylation and degradation of IκBα, a key factor accounting for the activation and translocation of nuclear factor κB (NF-κB) in endothelial cells. These findings indicated that histamine was able to synergistically augment bFGF-induced angiogenesis, and this action was linked to VEGF production through H1-receptor and the activation of endothelial nitric oxide synthase (eNOS), p38 MAPK, and IκBα in endothelial cells.


Medical insurance as a direction of reforming the health system in Ukraine.
Introduction: The right to live, the right to healthcare and medical care insurance, which are affirmed at the constitutional level in Ukraine, are exercised by organizing the healthcare system with the due consideration of all social groups of people. The current state of healthcare funding in Ukraine does not encourage the conditions under which the quality medical care is provided to the population as needed, especially to the socially disadvantaged group of people. The formation of marketing system of management in Ukraine, the declaration of it as a socially-oriented country, results in the necessity to carry out healthcare reforms and to implement new systems of funding. The special emphasis in the process has to be given to the development of the insurance. The aim: To study, to evaluate and elaborate proposals towards the justification of the changes in the healthcare funding through the reforming the system of medical insurance. Materials and methods: Laws and regulations of Ukraine and related countries are analyzed in the article (by methods of comparison, analysis, synthesis, deductive approach, and scientific abstraction and generalization). Review: The main forms of healthcare funding (on account of voluntary, compulsory and mixed insurance) were found out. Also, the special features of medical insurance in different countries based on the generalized models were investigated. As a part of the research, the condition of medical (voluntary and compulsory) insurance in Ukraine was analyzed and, as a result, the issues hindering its development were defined. Conclusions: The model of insurance for implementation in Ukraine had been defined, as well as the condition of reforming system in compulsory insurance such as "taxesbudget-agency" with the stages had also been estimated. The possible consequences of medical reforming in Ukraine and the possible ways to improve the process of insurance in medical area were specified.


Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats.
The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 x 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT(1A) agonist 8-OH-DPAT (250 microg/kg but not 125 microg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT(1A) receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA.


Physician Attitudes Toward Urinary Incontinence Identification.
Urinary incontinence (UI) is a prevalent condition. Urinary incontinence impacts health, quality of life, and financial resources. Most barriers research is evaluated from the patient perspective. Research from physician perspective is needed to determine how best to address UI barriers. This study aimed to elucidate physician barriers to UI identification and treatment. After institutional review board waiver, we surveyed 78 NorthShore University HealthSystem primary care physicians. The survey was designed to assess physician comfort, familiarity with UI, and current practice patterns. Fifty-five (71%) of the 78 physicians completed the survey. Most indicated that they clearly understood UI and that UI was a common problem in their practice. Fifty-six percent of the physicians were very comfortable inquiring about UI. Only 19% of the physicians were very comfortable diagnosing UI and 11% of the physicians were very comfortable treating UI. Fifty-nine percent of the physicians agreed that differentiating the different types of UI is difficult and 69% of the physicians believed that managing UI is difficult. However, only 26% of the physicians agreed that managing UI takes too much time. Overall, 65% of the physicians would like to diagnose and treat UI more in their practices. The most common barriers listed were (1) "not familiar with algorithm available for treatment," (2) "no good screening tool," and (3) "uncomfortable with diagnosis and treatment." We initially thought that time would be the biggest barrier to care for UI, but we identified discomfort with diagnosis and treatment as barriers. The most common barrier was the lack of an accessible algorithm. Attention to physician education implementation of a screening tool algorithm for treatment of UI could improve UI identification.


Acute-to-chronic species sensitivity distribution extrapolation.
Seeking to make greater use of available data for risk assessment of substances, we constructed, for the situation in which chronic data are limited or even nonexistent but acute data are relatively large, an acute to chronic transformation (ACT) methodology based on the concept of species sensitivity distributions (SSDs). This ACT methodology uses a comparison of acute and chronic SSDs, separately for vertebrate data (with 22 substances) and for invertebrate data (with 15 substances). Rather than comparing an acute toxicity value with a chronic value, as when calculating an acute to chronic ratio (ACR), samples of acute and chronic data corresponding to the same category of species were compared. Starting from a sample of acute data, the ACT methodology showed relationships that enable the creation of a sample of predicted chronic values. This sample can then be used to calculate a predicted chronic hazardous concentration potentially affecting 5% of species (HC5%), just as with a sample of real chronic toxicity values. This ACT approach was tested on 11 substances. For each substance, the real chronic HC5% and the predicted chronic HC5% were calculated and compared. The ratio between chronic HC5% and ACT HC5% was, on average, 1.6 and did not exceed 4.4 for the 11 substances studied.


Exploring the Relationship Between Athletic Identity and Beliefs About Rehabilitation Overadherence in College Athletes.
Athletic identity has been associated with rehabilitation overadherence in college athletes. To explore which constructs of athletic identity predict rehabilitation overadherence, gauge athletes' views of the most salient aspect of their athletic participation, and understand their perceptions of the reasons they adhere to their rehabilitation program. Cross-sectional, mixed methods. University athletic training clinics and online. Currently injured college athletes (N = 80; 51 male, 29 female). Athletic Identity Measurement Scale (AIMS), Rehabilitation Overadherence Questionnaire (ROAQ), and 2 open-ended questions about athletic participation and rehabilitation adherence. Higher levels of athletic identity were associated with higher levels of rehabilitation overadherence (r = .29, P = .009). Hierarchical multiple regression used on AIMS subscales to predict ROAQ subscales did not reveal a significant model for the subscale "ignore practitioner recommendations." However, a significant model was revealed for the subscale "attempt an expedited rehabilitation," F5,73 = 2.56, P = .04, R2 = .15. Negative affectivity was the only significant contribution to the equation (β = 0.33, t = 2.64, P = .01). Content analysis revealed that bodily benefits, sport participation, personal achievement, social relationships, and athlete status were perceived to be the most important aspects of being an athlete. The themes of returning to competition, general health, and relationship beliefs were identified as the major factors for adhering to a rehabilitation program. Negative affectivity accounted for a significant but low amount of variance for rehabilitation overadherence, suggesting that athletic trainers should pay attention to personal variables such as athletic identity that might influence the rehabilitation process. Using the knowledge of why athletes adhere to their rehabilitation and what is most important to them about being an athlete, athletic trainers can use appropriate interventions to facilitate proper rehabilitation adherence.


[Yersinia enterocolitica infection has taken hold even in our country].
The Yersinia enterocolitis is a kind of disease whose diffusion is gradually increasing in North Europe. The authors relates about the outcomes of a serum-immunologic research conducted during the period 1982-84 on a sample of 965 adults coming from three different italian districts (Roma, Siena, Napoli) and 65 children coming from Napoli. They interpret antibody titers painted out by their research comparing them with ones reported in bibliography. The issue of this research, even if it was conducted only in three bordering central-southern Italy regions, can anticipate an indicative epidemiological image of this Country.


Automatic control of a drop-foot stimulator based on angle measurement using bioimpedance.
The topic of this contribution is iterative learning control of a drop-foot stimulator in which a predefined angle profile during the swing phase is realized. Ineffective dorsiflexion is compensated by feedback-controlled stimulation of the muscle tibialis anterior. The ankle joint measurement is based on changes in the bioimpedance (BI) caused by leg movements. A customized four-channel BI measurement system was developed. The suggested control approach and the new measurement method for the joint angle were successfully tested in preliminary experiments with a neurologically intact subject. Reference angle measurements were taken with a marker-based optical system. An almost linear relation between joint angle and BI was found for the angle range applicable during gait. The desired angle trajectory was closely tracked by the iterative learning controller after three gait cycles. The final root mean square tracking error was below 5 degrees.


Numerical model built for the simulation of the earth magnetopause by lobster-eye-type soft X-ray imager onboard SMILE satellite.
Solar wind magnetosphere ionosphere link explorer (SMILE) scientific satellite is dedicated to observe solar wind-magnetosphere coupling. The key payload, soft X-ray imager (SXI), is designed to map the location, shape, and motion of dayside magnetospheric boundaries by Angel-type lobster-eye optical system. Contrast to traditional Wolter-type X-ray telescope with very narrow field-of-view, the lobster-eye-type optics has a unique capability of providing wide field of view for panoramic imaging with moderate spatial resolution in soft X-ray band. Since the lobster-eye optics focus X-ray by reflecting of the inner walls of the micro-channel array shaped in spherical surface, traditional optical design tools can't well match to the requirements of simulation for SXI. In this paper, a 3D Angel-type lobster-eye model is designed for simulation of lobster-eye optics and its capability is demonstrated for the applying scenarios including the imaging of point light source, surface light source with uniform and non-uniform intensity distribution. The simulation results are well consistent with those of theoretical estimate.


Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives.
Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects. Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition. In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC50:0.42 nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site.


Low doses of the neonicotinoid insecticide imidacloprid induce ROS triggering neurological and metabolic impairments in Drosophila.
Declining insect population sizes are provoking grave concern around the world as insects play essential roles in food production and ecosystems. Environmental contamination by intense insecticide usage is consistently proposed as a significant contributor, among other threats. Many studies have demonstrated impacts of low doses of insecticides on insect behavior, but have not elucidated links to insecticidal activity at the molecular and cellular levels. Here, the histological, physiological, and behavioral impacts of imidacloprid are investigated in Drosophila melanogaster, an experimental organism exposed to insecticides in the field. We show that oxidative stress is a key factor in the mode of action of this insecticide at low doses. Imidacloprid produces an enduring flux of Ca2+ into neurons and a rapid increase in levels of reactive oxygen species (ROS) in the larval brain. It affects mitochondrial function, energy levels, the lipid environment, and transcriptomic profiles. Use of RNAi to induce ROS production in the brain recapitulates insecticide-induced phenotypes in the metabolic tissues, indicating that a signal from neurons is responsible. Chronic low level exposures in adults lead to mitochondrial dysfunction, severe damage to glial cells, and impaired vision. The potent antioxidant, N-acetylcysteine amide (NACA), reduces the severity of a number of the imidacloprid-induced phenotypes, indicating a causal role for oxidative stress. Given that other insecticides are known to generate oxidative stress, this research has wider implications. The systemic impairment of several key biological functions, including vision, reported here would reduce the resilience of insects facing other environmental challenges.


Post-diagnostic management and follow-up care for autism spectrum disorder.
Paediatricians and other primary care providers are well positioned to provide or coordinate ongoing medical and psychosocial care and support services for children with autism spectrum disorder (ASD). This statement provides recommendations and information on a range of interventions and resources, to help paediatric care providers optimize care for children with ASD and support their families. The management of ASD includes treating medical and psychiatric co-morbidities, behavioural and developmental interventions, and providing supportive social care services to enhance quality of life for affected children and families.


Unsanctifying the sanctuary: challenges and opportunities with brain metastases.
While the use of targeted therapies, particularly radiosurgery, has broadened therapeutic options for CNS metastases, patients respond minimally and prognosis remains poor. The inability of many systemic chemotherapeutic agents to penetrate the blood-brain barrier (BBB) has limited their use and allowed brain metastases to become a burgeoning clinical challenge. Adequate preclinical models that appropriately mimic the metastatic process, the BBB, and blood-tumor barriers (BTB) are needed to better evaluate therapies that have the ability to enhance delivery through or penetrate into these barriers and to understand the mechanisms of resistance to therapy. The heterogeneity among and within different solid tumors and subtypes of solid tumors further adds to the difficulties in determining the most appropriate treatment approaches and methods of laboratory and clinical studies. This review article discusses therapies focused on prevention and treatment of CNS metastases, particularly regarding the BBB, and the challenges and opportunities these therapies present.


Mechanism of semantic processing of lexicalized and novel compound words: An eye movement study.
The integration of semantic information of compound words with context is a crucial aspect of reading comprehension. In two eye-tracking experiments, we used two-character and four-character Chinese lexicalized and novel compound words to investigate how Chinese readers integrate semantic information of compound words with contexts in the present study. By manipulating the temporary plausibility of the first constituent through varying the preceding verb, we aimed to investigate how readers process semantic information of compound words during normal reading. A significant plausibility effect pattern in the first constituent region was observed for the four-character novel words, but not for the lexicalized compound words and two-character novel compound words. However, for both two-character and four-character novel compound words, a reverse plausibility effect was found in the second constituent region. This was not the case for lexicalized compound words. These results indicate that novel compound words are integrated with the context in a decompositional manner, while lexicalized compound words are integrated holistically. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Beta-blockade and exercise capacity in patients with mitral stenosis in sinus rhythm.
The study aim was to determine whether beta-blocker treatment (atenolol) improves cardiopulmonary exercise performance and ventilatory response in patients with mitral stenosis in sinus rhythm. A prospective study comparing the results of cardiopulmonary exercise tests (CPETs) was performed before and after atenolol therapy in 17 patients in NYHA classes I and II with mitral stenosis in sinus rhythm. Transthoracic echocardiography was performed pre-study, and left ventricular diameters, ejection fraction and mitral valve area monitored. CPETs (Naughton protocol) were performed by two different investigators before and after one-week atenolol therapy (50 mg/day). The second investigator was blinded to the result of the baseline test. O2 consumption, CO2 production, ventilatory parameters and respiratory exchange ratios were measured on line. Maximal O2 uptake (VO2max) did not differ significantly before and after beta-blockade (median 16.8 and 15.0 ml/kg/min, respectively. Median heart rate at rest (72 versus 55 beats/min; p = 0.0003) and during peak exercise (153 versus 105 beats/min; p = 0.0003), and anaerobic threshold (10 versus 8.9 ml/kg/min; p = 0.02) were lower with beta-blockade compared with the baseline state. Minute ventilation at maximum exercise (41 versus 40 l/min) and ventilatory equivalent for CO2 (34 versus 35) were unchanged with atenolol therapy, indicating no improvement in ventilatory performance. When patients were grouped into those in whom VO2max was improved with atenolol therapy (n = 7) and those in whom it was impaired (n = 10), there were no inter-group differences with respect to age, left ventricular function, severity of mitral stenosis, NYHA class and grade of beta-blockade reached. Four patients felt symptomatically worse during atenolol treatment (lower NYHA functional class). Beta-blockade does not improve exercise tolerance in patients with mitral stenosis in sinus rhythm. In addition, ventilatory performance does not change with treatment.


Risk of tuberculosis infection and tuberculous meningitis after discontinuation of Bacillus Calmette-Guerin in Beijing.
In Beijing, the notification rate of smear-positive tuberculosis (TB) has been below 20 per 100,000 since 1986, and continues to decline. To accurately measure the risk of TB infection in a population in which the results of tuberculin skin testing were not confounded by vaccination with Bacillus Calmette-Guerin (BCG), BCG vaccination at birth was discontinued from 1988 in Shun-yi County. In 1995, the prevalence of TB infection among 12,836 primary school children aged 6 to 7 yr and without BCG scars was 1.4%, giving an estimated annual risk of infection of 0.19% (95% confidence interval: 0.16 to 0.22%). The prevalence of TB infection in children aged 5 to 9 yr in Beijing in 1950 was 46%. The number of cases of tuberculous meningitis did not increase after discontinuation of BCG. We conclude that discontinuation of BCG had no detectable harmful effects, and that control of TB in Beijing has markedly reduced the prevalence of TB infection since 1950.


Scanning strategies do not modulate face identification: eye-tracking and near-infrared spectroscopy study.
During face identification in humans, facial information is sampled (seeing) and handled (processing) in ways that are influenced by the kind of facial image type, such as a self-image or an image of another face. However, the relationship between seeing and information processing is seldom considered. In this study, we aimed to reveal this relationship using simultaneous eye-tracking measurements and near-infrared spectroscopy (NIRS) in face identification tasks. 22 healthy adult subjects (8 males and 14 females) were shown facial morphing movies in which an initial facial image gradually changed into another facial image (that is, the subject's own face was changed to a familiar face). The fixation patterns on facial features were recorded, along with changes in oxyhemoglobin (oxyHb) levels in the frontal lobe, while the subjects identified several faces. In the self-face condition (self-face as the initial image), hemodynamic activity around the right inferior frontal gyrus (IFG) was significantly greater than in the familiar-face condition. On the other hand, the scanning strategy was similar in almost all conditions with more fixations on the eyes and nose than on other areas. Fixation time on the eye area did not correlate with changes in oxyHb levels, and none of the scanning strategy indices could estimate the hemodynamic changes. We conclude that hemodynamic activity, i.e., the means of processing facial information, is not always modulated by the face-scanning strategy, i.e., the way of seeing, and that the right IFG plays important roles in both self-other facial discrimination and self-evaluation.


An insight into the sialome of Simulium guianense (DIPTERA:SIMulIIDAE), the main vector of River Blindness Disease in Brazil.
Little is known about the composition and function of the saliva in black flies such as Simulium guianense, the main vector of river blindness disease in Brazil. The complex salivary potion of hematophagous arthropods counteracts their host's hemostasis, inflammation, and immunity. Transcriptome analysis revealed ubiquitous salivary protein families--such as the Antigen-5, Yellow, Kunitz domain, and serine proteases--in the S. guianense sialotranscriptome. Insect-specific families were also found. About 63.4% of all secreted products revealed protein families found only in Simulium. Additionally, we found a novel peptide similar to kunitoxin with a structure distantly related to serine protease inhibitors. This study revealed a relative increase of transcripts of the SVEP protein family when compared with Simulium vittatum and S. nigrimanum sialotranscriptomes. We were able to extract coding sequences from 164 proteins associated with blood and sugar feeding, the majority of which were confirmed by proteome analysis. Our results contribute to understanding the role of Simulium saliva in transmission of Onchocerca volvulus and evolution of salivary proteins in black flies. It also consists of a platform for mining novel anti-hemostatic compounds, vaccine candidates against filariasis, and immuno-epidemiologic markers of vector exposure.


NADPH oxidase of human neutrophils. Subcellular localization and characterization of an arachidonate-activatable superoxide-generating system.
The superoxide-forming NADPH oxidase of human neutrophils was studied in subcellular fractions of unstimulated cells. Purified neutrophils were disrupted by nitrogen cavitation and separated on Percoll density gradients into four fractions: alpha, azurophil granules; beta, mostly specific granules; gamma, plasma membrane, and cytosol. NADPH-dependent O2-. formation by these fractions was quantitated as the rate of superoxide dismutase-inhibitable reduction of ferricytochrome c. In the presence of cytosol, NADPH, and either arachidonic acid (optimum 90 microM) or sodium dodecyl sulfate (optimum 160 microM), 70-75% of the oxidase was in the beta fraction and about 25% was in the gamma fraction. A similar distribution was found for cytochrome b559 and FAD, two putative components of the oxidase. The reaction rates observed with arachidonic acid activation were sufficient to account for 25-75% of the O2-. generated by intact neutrophils. The properties of the beta and gamma enzymes were similar and closely resembled those of the oxidase in intact neutrophils or disrupted prestimulated cells. These included resistance to azide and cyanide, a pH optimum of 7.4, and a preference for NADPH (Km approximately 40-45 microM) rather than NADH (Km approximately 2.5 mM) as the electron donor. The combination of beta and gamma fractions displayed additive activity. The activatable oxidase required Mg2+ but not Ca2+. ATP was required for maximum reaction rates. When beta and gamma membranes were preincubated with cytosol and arachidonic acid in the presence of millimolar Mg2+ and then ultracentrifuged membrane-bound O2-. -forming activity was recovered in the pellet and the enzyme required only NADPH (i.e. no cytosol, arachidonic acid, or Mg2+) for expression of activity. These data suggest that cytosol contains a Mg2+-dependent oxidase-activating factor. Molecular sieve chromatography of cytosol indicated a single peak of activity (i.e. ability to activate O2-. generation by beta and/or gamma fraction) eluting with molecules of about 10,000 daltons.


Action trees and moral judgment.
It has sometimes been suggested that people represent the structure of action in terms of an action tree. A question now arises about the relationship between this action tree representation and people's moral judgments. A natural hypothesis would be that people first construct a representation of the action tree and then go on to use this representation in making moral judgments. The present paper argues for a more complex view. Specifically, the paper reports a series of experimental studies that appear to show that people's moral judgments can actually impact their representations of the action tree itself.


What effect does medicine advice provided by UK Medicines Information pharmacists have on prescriber practice and patient care: a qualitative primary care study.
UK Medicines Information (UKMI) is pharmacist-led service funded by the National Health Service providing evidence-based advice about medicines to health care professionals. Service evaluations have repeatedly shown high user satisfaction but few studies have assessed how this advice influences the care patients receive. Furthermore, no study has assessed how prescribers actually use this information in shaping their decision making. The aim was to explore how UKMI advice influences prescriber decision making and patient care. Doctors and dentists (referred to as prescribers) working in primary care in England and Wales who received reactive medicines advice from a medicines information centre were contacted by telephone to determine how they used the advice provided. Forty semi-structured interviews were analysed and coded using constant comparative content analysis. Five key themes were identified that affected prescriber decision making, these were: prescriber action, patient outcome, medicines information advice, risk management and time factors. Prescribers acted directly on the advice provided enabling them to provide the right care for their patients. Advice had a positive effect on how they viewed a medication problem and empowered them to make decisions that appeared to confer greater confidence in managing patient problems. A favourable patient outcome was described by over half of the prescribers, for example, the advice enabled them to provide patient reassurance, avoid a potential allergic reaction, stabilize the patient's condition or stop treatment. Medicines information advice empowered prescribers in helping them to make decisions about medicines that shaped patient care.


Molecular cloning and characterization of human podocalyxin-like protein. Orthologous relationship to rabbit PCLP1 and rat podocalyxin.
Human renal cortex and heart cDNA libraries were screened for a human homolog of rabbit PCLP1 using the rabbit PCLP1 cDNA as a probe. Clones spanning 5869 base pairs with an open reading frame coding for a 528-amino acid peptide were obtained. The putative peptide contains a potential signal peptide and a single membrane-spanning region. The extracellular domain contains multiple potential sites for N- and O-linked glycosylation and 4 cysteines for potential disulfide bonding similar to rabbit PCLP1. On Northern blot a major transcript is seen at 5.9 kilobases. Antibodies to this protein show a doublet at 160/165 kDa on Western blots of human glomerular extract and a pattern of intense glomerular staining and vascular endothelial staining on immunofluorescence of human kidney sections. Comparison of the rabbit and human peptide sequences shows a high degree of identity in the transmembrane and intracellular domains (96%) with a lower degree of identity in the extracellular domain (36%). An antibody to the intracellular domain reacted across species (human, rabbit, and rat) and recognized both rabbit PCLP1 and rat podocalyxin. An interspecies Southern blot probed with a cDNA coding for the intracellular domain showed strong hybridization to all vertebrates tested in a pattern suggesting a single copy gene. We conclude that this cDNA and putative peptide represent the human homolog of rabbit PCLP1 and rat podocalyxin.


Tumor-infiltrating macrophages are associated with metastasis suppression in high-grade osteosarcoma: a rationale for treatment with macrophage activating agents.
High-grade osteosarcoma is a malignant primary bone tumor with a peak incidence in adolescence. Overall survival (OS) of patients with resectable metastatic disease is approximately 20%. The exact mechanisms of development of metastases in osteosarcoma remain unclear. Most studies focus on tumor cells, but it is increasingly evident that stroma plays an important role in tumorigenesis and metastasis. We investigated the development of metastasis by studying tumor cells and their stromal context. To identify gene signatures playing a role in metastasis, we carried out genome-wide gene expression profiling on prechemotherapy biopsies of patients who did (n = 34) and patients who did not (n = 19) develop metastases within 5 years. Immunohistochemistry (IHC) was performed on pretreatment biopsies from 2 additional cohorts (n = 63 and n = 16) and corresponding postchemotherapy resections and metastases. A total of 118/132 differentially expressed genes were upregulated in patients without metastases. Remarkably, almost half of these upregulated genes had immunological functions, particularly related to macrophages. Macrophage-associated genes were expressed by infiltrating cells and not by osteosarcoma cells. Tumor-associated macrophages (TAM) were quantified with IHC and associated with significantly better overall survival (OS) in the additional patient cohorts. Osteosarcoma samples contained both M1- (CD14/HLA-DRα positive) and M2-type TAMs (CD14/CD163 positive and association with angiogenesis). In contrast to most other tumor types, TAMs are associated with reduced metastasis and improved survival in high-grade osteosarcoma. This study provides a biological rationale for the adjuvant treatment of high-grade osteosarcoma patients with macrophage activating agents, such as muramyl tripeptide.


Physical cleansing reduces the mindset effect in problem-solving.
The present study investigated whether physical cleansing can reduce the mindset effect in problem-solving in two experiments. Both experiments followed the same procedure. In the first stage, participants formed a mindset through the Luchins' water-jar task (Experiment 1) or the idiom maze task (Experiment 2). The second stage is cleansing manipulation. In Experiment 1, participants were asked to clean their hands with wipes (cleansing condition) or examine the packaging of the wipes (no-cleansing condition). In Experiment 2, participants were asked to watch a washing-hands video (cleansing condition) or watch an examining-pen video (no-cleansing condition). At last, all participants completed the mindset effect test problems. The results showed that the participants in the cleansing condition were less affected by the mindset than those in the no-cleansing condition, indicating that physical cleansing reduced the mindset effect. Our results provide new evidence for the clean-slate effects and support the hypothesis that physical cleansing is an embodied process of psychological separation.


Sustainable food systems and nutrition in the 21st century: a report from the 22nd annual Harvard Nutrition Obesity Symposium.
Food systems are at the center of a brewing storm consisting of a rapidly changing climate, rising hunger and malnutrition, and significant social inequities. At the same time, there are vast opportunities to ensure that food systems produce healthy and safe food in equitable ways that promote environmental sustainability, especially if the world can come together at the UN Food Systems Summit in late 2021 and make strong and binding commitments toward food system transformation. The NIH-funded Nutrition Obesity Research Center at Harvard and the Harvard Medical School Division of Nutrition held their 22nd annual Harvard Nutrition Obesity Symposium entitled "Global Food Systems and Sustainable Nutrition in the 21st Century" in June 2021. This article presents a synthesis of this symposium and highlights the importance of food systems to addressing the burden of malnutrition and noncommunicable diseases, climate change, and the related economic and social inequities. Transformation of food systems is possible, and the nutrition and health communities have a significant role to play in this transformative process.