Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate

What Was I Thinking? Eye-Tracking Experiments Underscore the Bias that Architecture Exerts on Nuclear Grading in Prostate Cancer

We previously reported that nuclear grade assignment of prostate carcinomas is subject to a cognitive bias induced by the tumor architecture. Here, we asked whether this bias is mediated by the non-conscious selection of nuclei that “match the expectation” induced by the inadvertent glance at the tumor architecture. 20 pathologists were asked to grade nuclei in high power fields of 20 prostate carcinomas displayed on a computer screen. Unknown to the pathologists, each carcinoma was shown twice, once before a background of a low grade, tubule-rich carcinoma and once before the background of a high grade, solid carcinoma. Eye tracking allowed to identify which nuclei the pathologists fixated during the 8 second projection period. For all 20 pathologists, nuclear grade assignment was significantly biased by tumor architecture. Pathologists tended to fixate on bigger, darker, and more irregular nuclei when those were projected before kigh grade, solid carcinomas than before low grade, tubule-rich carcinomas (and vice versa). However, the morphometric differences of the selected nuclei accounted for only 11% of the architecture-induced bias, suggesting that it can only to a small part be explained by the unconscious fixation on nuclei that “match the expectation”. In conclusion, selection of « matching nuclei » represents an unconscious effort to vindicate the gravitation of nuclear grades towards the tumor architecture

Associated Factors for Falls among the Community-Dwelling Older People Assessed by Annual Geriatric Health Examinations

BACKGROUND: Falls are very common among the older people. Nearly one-third older people living in a community fall each year. However, few studies have examined factors associated with falls in a community-dwelling population of older Taiwanese adults. OBJECTIVES: To identify the associated factors for falls during the previous 12 months among the community-dwelling Taiwanese older people receiving annual geriatric health examinations. PARTICIPANTS: People aged sixty-five years or older, living in the community, assessed by annual geriatric health examinations METHODS: 1377 community-dwellers aged ≥65 years who received annual geriatric health examinations at one hospital in northern Taiwan between March and November of 2008. They were asked about their history of falls during the year prior to their most recent health examination. RESULTS: The average age of the 1377 participants was 74.9±6.8 years, 48.9% of which were women. Three-hundred and thirteen of the participants (22.7%) had at least one fall during the previous year. Multivariate analysis showed that odds ratio for the risk of falling was 1.94 (95% CI 1.36-2.76) when the female gender group is compared with the male gender group. The adjusted odds ratios of age and waist circumference were 1.03 (95% CI 1.00-1.06) and 1.03 (95% CI 1.01-1.05) respectively. The adjusted odds ratios of visual acuity, Karnofsky scale, and serum albumin level were 0.34 (95% CI 0.15-0.76), 0.94 (95% CI 0.89-0.98), and 0.37 (95% CI 0.18-0.76) respectively. Larger waist circumference, older age, female gender, poorer visual acuity, lower score on the Karnofsky Performance Scale, and lower serum albumin level were the independent associated factors for falls. CONCLUSION: In addition to other associated factors, waist circumference should be included as a novel risk factor for falls

Combination antibiotic therapy for community-acquired pneumonia

Community-acquired pneumonia (CAP) is a common and potentially serious illness that is associated with morbidity and mortality. Although medical care has improved during the past decades, it is still potentially lethal. Streptococcus pneumoniae is the most frequent microorganism isolated. Treatment includes mandatory antibiotic therapy and organ support as needed. There are several antibiotic therapy regimens that include β-lactams or macrolides or fluoroquinolones alone or in combination. Combination antibiotic therapy achieves a better outcome compared with monotherapy and it should be given in the following subset of patients with CAP: outpatients with comorbidities and previous antibiotic therapy, nursing home patients with CAP, hospitalized patients with severe CAP, bacteremic pneumococcal CAP, presence of shock, and necessity of mechanical ventilation. Better outcome is associated with combination therapy that includes a macrolide for wide coverage of atypical pneumonia, polymicrobial pneumonia, or resistant Streptococcus pneumoniae. Macrolides have shown different properties other than antimicrobial activity, such as anti-inflammatory properties. Although this evidence comes from observational, most of them retrospective and nonblinded studies, the findings are consistent. Ideally, a prospective, multicenter, randomized trial should be performed to confirm these findings

Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Monoamine oxidase A (MAO-A), a mitochondrial enzyme that degrades monoamines including neurotransmitters, is highly expressed in basal cells of the normal human prostatic epithelium and in poorly differentiated (Gleason grades 4 and 5), aggressive prostate cancer (PCa). Clorgyline, an MAO-A inhibitor, induces secretory differentiation of normal prostate cells. We examined the effects of clorgyline on the transcriptional program of epithelial cells cultured from high grade PCa (E-CA).</p> <p>Methods</p> <p>We systematically assessed gene expression changes induced by clorgyline in E-CA cells using high-density oligonucleotide microarrays. Genes differentially expressed in treated and control cells were identified by Significance Analysis of Microarrays. Expression of genes of interest was validated by quantitative real-time polymerase chain reaction.</p> <p>Results</p> <p>The expression of 156 genes was significantly increased by clorgyline at all time points over the time course of 6 – 96 hr identified by Significance Analysis of Microarrays (SAM). The list is enriched with genes repressed in 7 of 12 oncogenic pathway signatures compiled from the literature. In addition, genes downregulated ≥ 2-fold by clorgyline were significantly enriched with those upregulated by key oncogenes including beta-catenin and ERBB2, indicating an anti-oncogenic effect of clorgyline. Another striking effect of clorgyline was the induction of androgen receptor (AR) and classic AR target genes such as prostate-specific antigen together with other secretory epithelial cell-specific genes, suggesting that clorgyline promotes differentiation of cancer cells. Moreover, clorgyline downregulated EZH2, a critical component of the Polycomb Group (PcG) complex that represses the expression of differentiation-related genes. Indeed, many genes in the PcG repression signature that predicts PCa outcome were upregulated by clorgyline, suggesting that the differentiation-promoting effect of clorgyline may be mediated by its downregulation of EZH2.</p> <p>Conclusion</p> <p>Our results suggest that inhibitors of MAO-A, already in clinical use to treat depression, may have potential application as therapeutic PCa drugs by inhibiting oncogenic pathway activity and promoting differentiation.</p

Biology, Methodology or Chance? The Degree Distributions of Bipartite Ecological Networks

The distribution of the number of links per species, or degree distribution, is widely used as a summary of the topology of complex networks. Degree distributions have been studied in a range of ecological networks, including both mutualistic bipartite networks of plants and pollinators or seed dispersers and antagonistic bipartite networks of plants and their consumers. The shape of a degree distribution, for example whether it follows an exponential or power-law form, is typically taken to be indicative of the processes structuring the network. The skewed degree distributions of bipartite mutualistic and antagonistic networks are usually assumed to show that ecological or co-evolutionary processes constrain the relative numbers of specialists and generalists in the network. I show that a simple null model based on the principle of maximum entropy cannot be rejected as a model for the degree distributions in most of the 115 bipartite ecological networks tested here. The model requires knowledge of the number of nodes and links in the network, but needs no other ecological information. The model cannot be rejected for 159 (69%) of the 230 degree distributions of the 115 networks tested. It performed equally well on the plant and animal degree distributions, and cannot be rejected for 81 (70%) of the 115 plant distributions and 78 (68%) of the animal distributions. There are consistent differences between the degree distributions of mutualistic and antagonistic networks, suggesting that different processes are constraining these two classes of networks. Fit to the MaxEnt null model is consistently poor among the largest mutualistic networks. Potential ecological and methodological explanations for deviations from the model suggest that spatial and temporal heterogeneity are important drivers of the structure of these large networks

Sodium Chloride Inhibits the Growth and Infective Capacity of the Amphibian Chytrid Fungus and Increases Host Survival Rates

The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0–5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii) in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1–4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation

The role of routine post-natal abdominal ultrasound for newborns in a resource-poor setting: a longitudinal study

<p>Abstract</p> <p>Background-</p> <p>Neonatal abdominal ultrasound is usually performed in Nigeria to investigate neonatal symptoms rather than as a follow up to evaluate fetal abnormalities which were detected on prenatal ultrasound. The role of routine obstetric ultrasonography in the monitoring of pregnancy and identification of fetal malformations has partly contributed to lowering of fetal mortality rates. In Nigeria which has a high maternal and fetal mortality rate, many pregnant women do not have ante-natal care and not infrequently, women also deliver their babies at home and only bring the newborns to the clinics for immunization. Even when performed, most routine obstetric scans are not targeted towards the detection of fetal abnormalities.</p> <p>The aim of the present study is to evaluate the benefit of routinely performing abdominal scans on newborns with a view to detecting possible abnormalities which may have been missed ante-natally.</p> <p>Methods-</p> <p>This was a longitudinal study of 202 consecutive, apparently normal newborns. Routine clinical examination and abdominal ultrasound scans were performed on the babies by their mother's bedside, before discharge. Neonates with abnormal initial scans had follow-up scans.</p> <p>Results-</p> <p>There were 108 males and 94 females. There were 12 (5.9%) abnormal scans seen in five male and seven female neonates. Eleven of the twelve abnormalities were in the kidneys, six on the left and five on the right. Three of the four major renal anomalies- absent kidney, ectopic/pelvic kidney and two cases of severe hydronephrosis were however on the left side. There was one suprarenal abnormality on the right suspected to be a possible infected adrenal haemorrage. Nine of the abnormal cases reported for follow- up and of these, two cases had persistent severe abnormalities.</p> <p>Conclusions-</p> <p>This study demonstrated a 5.9% incidence of genito urinary anomalies on routine neonatal abdominal ultrasound in this small population. Routine obstetric USS is very useful but inadequate availability of skilled personnel and cost implications create great challenges in poor resource settings like Nigeria. However, awareness should be created so that parents who can afford such investigations can make informed decisions.</p

β-Adrenoreceptor Stimulation Mediates Reconsolidation of Social Reward-Related Memories

In recent years, the notion that consolidated memories become transiently unstable after retrieval and require reconsolidation to persist for later use has received strong experimental support. To date, the majority of studies on reconsolidation have focused on memories of negative emotions, while the dynamics of positive memories have been less well studied. Social play, the most characteristic social behavior displayed by young mammals, is important for social and cognitive development. It has strong rewarding properties, illustrated by the fact that it can induce conditioned place preference (CPP). In order to understand the dynamics of positive social memories, we evaluated the effect of propranolol, a β-adrenoreceptor antagonist known to influence a variety of memory processes, on acquisition, consolidation, retrieval and reconsolidation of social play-induced CPP in adolescent rats.Systemic treatment with propranolol, immediately before or after a CPP test (i.e. retrieval session), attenuated CPP 24 h later. Following extinction, CPP could be reinstated in saline--but not in propranolol-treated rats, indicating that propranolol treatment had persistently disrupted the CPP memory trace. Propranolol did not affect social play-induced CPP in the absence of memory retrieval or when administered 1 h or 6 h after retrieval. Furthermore, propranolol did not affect acquisition, consolidation or retrieval of social play-induced CPP.We conclude that β-adrenergic neurotransmission selectively mediates the reconsolidation, but not other processes involved in the storage and stability of social reward-related memories in adolescent rats. These data support the notion that consolidation and reconsolidation of social reward-related memories in adolescent rats rely on distinct neural mechanisms

Tree Resin Composition, Collection Behavior and Selective Filters Shape Chemical Profiles of Tropical Bees (Apidae: Meliponini)

The diversity of species is striking, but can be far exceeded by the chemical diversity of compounds collected, produced or used by them. Here, we relate the specificity of plant-consumer interactions to chemical diversity applying a comparative network analysis to both levels. Chemical diversity was explored for interactions between tropical stingless bees and plant resins, which bees collect for nest construction and to deter predators and microbes. Resins also function as an environmental source for terpenes that serve as appeasement allomones and protection against predators when accumulated on the bees' body surfaces. To unravel the origin of the bees' complex chemical profiles, we investigated resin collection and the processing of resin-derived terpenes. We therefore analyzed chemical networks of tree resins, foraging networks of resin collecting bees, and their acquired chemical networks. We revealed that 113 terpenes in nests of six bee species and 83 on their body surfaces comprised a subset of the 1,117 compounds found in resins from seven tree species. Sesquiterpenes were the most variable class of terpenes. Albeit widely present in tree resins, they were only found on the body surface of some species, but entirely lacking in others. Moreover, whereas the nest profile of Tetragonula melanocephala contained sesquiterpenes, its surface profile did not. Stingless bees showed a generalized collecting behavior among resin sources, and only a hitherto undescribed species-specific “filtering” of resin-derived terpenes can explain the variation in chemical profiles of nests and body surfaces from different species. The tight relationship between bees and tree resins of a large variety of species elucidates why the bees' surfaces contain a much higher chemodiversity than other hymenopterans