Effect of transmission setting and mixed species infections on clinical measures of malaria in Malawi

<p>Background: In malaria endemic regions people are commonly infected with multiple species of malaria parasites but the clinical impact of these Plasmodium co-infections is unclear. Differences in transmission seasonality and transmission intensity between endemic regions have been suggested as important factors in determining the effect of multiple species co-infections.</p> <p>Principal Findings: In order to investigate the impact of multiple-species infections on clinical measures of malaria we carried out a cross-sectional community survey in Malawi, in 2002. We collected clinical and parasitological data from 2918 participants aged >6 months, and applied a questionnaire to measure malaria morbidity. We examined the effect of transmission seasonality and intensity on fever, history of fever, haemoglobin concentration ([Hb]) and parasite density, by comparing three regions: perennial transmission (PT), high intensity seasonal transmission (HIST) and low intensity seasonal transmission (LIST). These regions were defined using multi-level modelling of PCR prevalence data and spatial and geo-climatic measures. The three Plasmodium species (P. falciparum, P. malariae and P. ovale) were randomly distributed amongst all children but not adults in the LIST and PT regions. Mean parasite density in children was lower in the HIST compared with the other two regions. Mixed species infections had lower mean parasite density compared with single species infections in the PT region. Fever rates were similar between transmission regions and were unaffected by mixed species infections. A history of fever was associated with single species infections but only in the HIST region. Reduced mean [Hb] and increased anaemia was associated with perennial transmission compared to seasonal transmission. Children with mixed species infections had higher [Hb] in the HIST region.</p> <p>Conclusions: Our study suggests that the interaction of Plasmodium co-infecting species can have protective effects against some clinical outcomes of malaria but that this is dependent on the seasonality and intensity of malaria transmission.</p&gt

Role of dorsomedial striatum neuronal ensembles in incubation of methamphetamine craving after voluntary abstinence

Abstract We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral striatum (DLS) and dorsomedial striatum (DMS) in this incubation. We trained rats to self-administer palatable food pellets (6 d, 6 h/d) and methamphetamine (12 d, 6 h/d). We then assessed relapse to methamphetamine seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent voluntary abstinence (using a discrete choice procedure between methamphetamine and food; 20 trials/d) for 19 d. We used in situ hybridization to measure the colabeling of the activity marker Fos with Drd1 and Drd2 in DMS and DLS after the tests. Based on the in situ hybridization colabeling results, we tested the causal role of DMS D1 and D2 family receptors, and DMS neuronal ensembles in "incubated" methamphetamine seeking, using selective dopamine receptor antagonists (SCH39166 or raclopride) and the Daun02 chemogenetic inactivation procedure, respectively. Methamphetamine seeking was higher after 21 d of voluntary abstinence than after 1 d (incubation of methamphetamine craving). The incubated response was associated with increased Fos expression in DMS but not in DLS; Fos was colabeled with both Drd1 and Drd2 DMS injections of SCH39166 or raclopride selectively decreased methamphetamine seeking after 21 abstinence days. In Fos-lacZ transgenic rats, selective inactivation of relapse test-activated Fos neurons in DMS on abstinence day 18 decreased incubated methamphetamine seeking on day 21. Results demonstrate a role of DMS dopamine D1 and D2 receptors in the incubation of methamphetamine craving after voluntary abstinence and that DMS neuronal ensembles mediate this incubation. SIGNIFICANCE STATEMENT: In human addicts, abstinence is often self-imposed and relapse can be triggered by exposure to drug-associated cues that induce drug craving. We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we used classical pharmacology, in situ hybridization, immunohistochemistry, and the Daun02 inactivation procedure to demonstrate a critical role of dorsomedial striatum neuronal ensembles in this new form of incubation of drug craving

Blockade of adenosine A2A receptors prevents protein phosphorylation in the striatum induced by cortical stimulation

©2006 Society for NeurosciencePrevious studies have shown that cortical stimulation selectively activates extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and immediate early gene expression in striatal GABAergic enkephalinergic neurons. In the present study, we demonstrate that blockade of adenosine A2A receptors with caffeine or a selective A2A receptor antagonist counteracts the striatal activation of cAMP– protein kinase A cascade (phosphorylation of the Ser845 residue of the glutamate receptor 1 subunit of the AMPA receptor) and mitogenactivated protein kinase (ERK1/2 phosphorylation) induced by the in vivo stimulation of corticostriatal afferents. The results indicate that A2A receptors strongly modulate the efficacy of glutamatergic synapses on striatal enkephalinergic neurons.This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Drug Abuse, Department of Health and Human Services

Generalization of Social Anxiety to Sporting and Athletic Situations: Gender, Sports Involvement, and Parental Pressure

Although researchers have documented that social anxiety may occur in a wide range of interpersonal and performance situations, little attention has been paid to the potential influence of social anxiety on participation in athletics or physical activity. The performance demands of sport and potential social evaluative nature of exercise make it likely that social anxiety would generalize to these situations. Given the physical and psychological benefits of engaging in regular physical activity, avoidance of such activities by socially anxious individuals may have profound health consequences. One-hundred and eighty undergraduate university students completed a battery of standardized social anxiety measures, and a series of 5-point Likert-type questions examining fear and avoidance of sporting and athletic situations. Results indicated that social anxiety and fear of negative evaluation were generally related to social-evaluative fears in sporting or athletic situations, particularly for women. Furthermore, social anxiety was positively correlated with avoidance of individual sporting activities, but not with avoidance of team activities. Further analyses revealed social anxiety did not differ by competition level. However, for men, familial pressure to play sports during high school was associated with higher fear of negative evaluation. Implications for the assessment and treatment of social anxiety disorder are discussed

Exploring the epigenetics of cocaine resistance

Drug addiction is known to have a heritable component and to run in families. However, a recent study in rats by Vassoler et al.(1) shows an unexpected result-that the sons of males who had self-administered cocaine had a reduced propensity to take this drug and a delay in their acquisition of drug-seeking behavior. The authors linked these behavioral changes to epigenetic changes in the sperm from cocaine-exposed males and in the brains of their male offspring. We asked four experts to comment on the results of this study and their implications for understanding how addictive phenotypes are inherited

Ruptured splenic artery aneurysms and the use of an adapted fast protocol in reproductive age women with hemodynamic collapse: Case series

Nontraumatic symptomatic hypotension in all patients requires prompt diagnosis and appropriate treatment for optimum outcome. The female population specifically has an expanded differential diagnosis that should be considered when these patients present with hemodynamic collapse. While the most common causes of hypotension in pregnant patients are dehydration, ruptured ectopic pregnancy, and placental and uterine abnormalities, less common nonobstetrical etiologies such as hepatic rupture and ruptured abdominal and visceral artery aneurysms should also be considered. Splenic artery aneurysms are associated with high rates of mortality and in cases of pregnancy, maternal and fetal mortality. These high rates can be attributed to the asymptomatic nature of the aneurysm, rapid deterioration after rupture, and frequent misdiagnosis. In patients with hemodynamic collapse, the role of traditional imaging is limited mainly due to the critical condition of the patient. Bedside ultrasound has emerged as a diagnostic imaging resource in patients with undifferentiated hypotension and in patients with traumatic injuries. However, its use has not been studied specifically in the female population. We present two patients with ruptured splenic artery aneurysms, discuss the role of bedside ultrasound in their management, and introduce a new ultrasound protocol for use in reproductive age female patients with hemodynamic collapse

Household Air Pollution and Acute Lower Respiratory Infections in Adults: A Systematic Review.

INTRODUCTION: Household air pollution from solid fuel burning kills over 4 million people every year including half a million children from acute lower respiratory infections. Although biologically plausible, it is not clear whether household air pollution is also associated with acute lower respiratory infections in adults. We systematically reviewed the literature on household air pollution and acute lower respiratory infection in adults to identify knowledge gaps and research opportunities. METHODS: Ten bibliographic databases were searched to identify studies of household air pollution and adult acute lower respiratory infection. Data were extracted from eligible studies using standardised forms. RESULTS: From 4617 titles, 513 abstracts and 72 full-text articles were reviewed. Eight studies met the inclusion criteria of which 2 found a significant adjusted increased risk of acute lower respiratory infection, 2 identified a univariate association whilst 4 found no significant association. Study quality was generally limited. Heterogeneity in methods and findings precluded meta-analysis. DISCUSSION: A systematic review of the literature found limited evidence for an association between household air pollution and risk of acute lower respiratory infection in adults. Additional research, with carefully defined exposure and outcome measures, is required to complete the risk profile caused by household air pollution in adults. REGISTRATION NUMBER: CRD42015028042

Distinct fos-expressing neuronal ensembles in the ventromedial prefrontal cortex mediate food reward and extinction memories

In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in “neuronal ensembles.” Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration.Wefirst trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area

Medial prefrontal cortex neuronal activation and synaptic alterations after stress-induced reinstatement of palatable food seeking: a study using c-fos-GFP transgenic female rats

Relapse to maladaptive eating habits during dieting is often provoked by stress and there is evidence for a role of ovarian hormones in stress responses and feeding. We studied the role of these hormones in stress-induced reinstatement of food seeking and medial prefrontal cortex (mPFC) neuronal activation in c-fos-GFP transgenic female rats, which express GFP in strongly activated neurons. Food-restricted ovariectomized or sham-operated c-fos-GFP rats were trained to lever-press for palatable food pellets. Subsequently, lever-pressing was extinguished and reinstatement of food seeking and mPFC neuronal activation was assessed after injections of the pharmacological stressor yohimbine (0.5-2 mg/kg) or pellet priming (1-4 noncontingent pellets). Estrous cycle effects on reinstatement were also assessed in wild-type rats. Yohimbine- and pellet-priming-induced reinstatement was associated with Fos and GFP induction in mPFC; both reinstatement and neuronal activation were minimally affected by ovarian hormones in both c-fos-GFP and wild-type rats. c-fos-GFP transgenic rats were then used to assess glutamatergic synaptic alterations within activated GFP-positive and nonactivated GFP-negative mPFC neurons following yohimbine-induced reinstatement of food seeking. This reinstatement was associated with reduced AMPA receptor/NMDA receptor current ratios and increased paired-pulse facilitation in activated GFP-positive but not GFP-negative neurons. While ovarian hormones do not appear to play a role in stress-induced relapse of food seeking in our rat model, this reinstatement was associated with unique synaptic alterations in strongly activated mPFC neurons. Our paper introduces the c-fos-GFP transgenic rat as a new tool to study unique synaptic changes in activated neurons during behavio

BSE situation and establishment of Food Safety Commission in Japan

Eight major policies were implemented by Japanese Government since Oct. 2001, to deal with bovine spongiform encephalopathy (BSE). These are; 1) Surveillance in farm by veterinarian, 2) Prion test at healthy 1.3mi cows/yr, by veterinarian, 3) Elimination of specified risk material (SRM), 4) Ban of MBM for production, sale use, 5) Prion test for fallen stocks, 6) Transparent information and traceability, 7) New Measures such as Food Safety Basic Law, and 8) Establish of Food Safety Commission in the Cabinet Office. At this moment, the extent of SRM risk has only been indicated by several reports employing tests with a limited sensitivity. There is still a possibility that the items in the SRM list will increase in the future, and this indiscriminately applies to Japanese cattle as well. Although current practices of SRM elimination partially guarantee total food safety, additional latent problems and imminent issues remain as potential headaches to be addressed. If the index of SRM elimination cannot guarantee reliable food safety, we have but to resort to total elimination of tissues from high risk-bearing and BSE-infected animals. However, current BSE tests have their limitations and can not yet completely detect high-risk and/or infected animals. Under such circumstances, tissues/wastes and remains of diseased, affected fallen stocks and cohort animals have to be eliminated to prevent BSE invading the human food chain systems. The failure to detect any cohort should never be allowed to occur, and with regular and persistent updating of available stringent records, we are at least adopting the correct and useful approach as a reawakening strategy to securing food safety. In this perspective, traceability based on a National Identification System is required