Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms : revival of an old drug

BACKGROUND: It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. METHODOLOGY: We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. PRINCIPAL FINDINGS: We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. CONCLUSIONSIGNIFICANCE: Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launche

Friendships fighting prejudice: A longitudinal perspective on adolescents’ cross-group friendships with immigrants

Increasingly, adolescents are growing up in multiethnic multicultural societies. While intergroup prejudice can threaten the multicultural societal cohesion, intergroup friendships are strong predictors of reduced prejudice. Thus, more research is needed to fully understand the development of intergroup friendships and their relations to less prejudicial attitudes. This study addressed two major developmental research questions: first, whether longitudinal patterns of intergroup friendships of native adolescents (i.e., whether or not a native German adolescent has a friendship with an immigrant at different points in time) relate to changes in rates of prejudice about immigrants. Second, whether these friendship patterns that unfold over time can be predicted by contact opportunities, attitudes, subjective norms, and perceived behavioral control assessed at the beginning of the study. The sample included 372 native German adolescents (14.7 years of age at first assessment, 62.3 % girls) who showed one of four friendship trajectories over the three annual assessments: they either maintained, gained, never had, or lost a friendship with an outgroup peer. In particular, results showed that adolescents who gained an intergroup friendship over the three time points showed a significant decrease in negative prejudice over the study. All four theorized predictors contributed to explain friendship trajectory membership. Generally, adolescents with many opportunities for contact, positive attitudes about contact, perceived positive social norms for contact, and high levels of behavioral control (self-efficacy) were more likely to maintain a friendship with an outgroup member than to follow any of the three other friendship trajectories (gain, lost, or never had). The pattern of predictions differed, however, depending on the specific pairs of friendship trajectories compared

Disaster Risks Research and Assessment to Promote Risk Reduction and Management

Natural hazard events lead to disasters when the events interact with exposed and vulnerable physical and social systems. Despite significant progress in scientific understanding of physical phenomena leading to natural hazards as well as of vulnerability and exposure, disaster losses due to natural events do not show a tendency to decrease. This tendency is associated with many factors including increase in populations and assets at risk as well as in frequency and/or magnitude of natural events, especially those related to hydro-meteorological and climatic hazards. But essentially disaster losses increase because some of the elements of the multidimensional dynamic disaster risk system are not accounted for risk assessments. A comprehensive integrated system analysis and periodic assessment of disaster risks at any scale, from local to global, based on knowledge and data/information accumulated so far, are essential scientific tools that can assist in recognition and reduction of disaster risks. This paper reviews and synthesizes the knowledge of natural hazards, vulnerabilities, and disaster risks and aims to highlight potential contributions of science to disaster risk reduction (DRR) in order to provide policy-makers with the knowledge necessary to assist disaster risk mitigation and disaster risk management (DRM)

Salivary Total Protease Activity Based on a Broad-Spectrum Fluorescence Resonance Energy Transfer Approach to Monitor Induction and Resolution of Gingival Inflammation

OBJECTIVE: Salivary total protease and chitinase activities were measured by a broad-spectrum fluorescence resonance energy transfer approach as predictors of induction and resolution of gingival inflammation in healthy individuals by applying an experimental human gingivitis model. METHODS: Dental biofilm accumulated (21 days, Induction Phase) by omitting oral hygiene practices followed by a 2-week Resolution Phase to restore gingival health in an experimental gingivitis study. Plaque accumulation, as assessed by the Turesky Modification of the Quigley-Hein Plaque Index (TQHPI), and gingival inflammation, assessed using the Modified Gingival Index (MGI), scores were recorded and unstimulated saliva was collected weekly. Saliva was analysed for total protein, albumin, total protease activity and chitinase activity (n = 18). RESULTS: The TQHPI and MGI scores, as well as total protease activity, increased until day 21. After re-establishment of oral hygiene, gingival inflammation levels returned to values similar to baseline (day 0). Levels of protease activity decreased significantly, but not to baseline values. Furthermore, 'fast' responders, who responded immediately to plaque, exhibited significantly higher proteolytic activity throughout the experimental course than 'slow' responders, who showed a lagged inflammatory response. CONCLUSION: The results indicate that differential inflammatory responses encompass inherent variations in total salivary proteolytic activities, which could be further utilised in contemporary diagnostic, prognostic and treatment modalities for periodontal diseases

Is it adaptive to disengage from demands of social change? Adjustment to developmental barriers in opportunity-deprived regions

This paper investigates how individuals deal with demands of social and economic change in the domains of work and family when opportunities for their mastery are unfavorable. Theoretical considerations and empirical research suggest that with unattainable goals and unmanageable demands motivational disengagement and self-protective cognitions bring about superior outcomes than continued goal striving. Building on research on developmental deadlines, this paper introduces the concept of developmental barriers to address socioeconomic conditions of severely constrained opportunities in certain geographical regions. Mixed-effects methods were used to model cross-level interactions between individual-level compensatory secondary control and regional-level opportunity structures in terms of social indicators for the economic prosperity and family friendliness. Results showed that disengagement was positively associated with general life satisfaction in regions that were economically devastated and has less than average services for families. In regions that were economically well off and family-friendly, the association was negative. Similar results were found for self-protection concerning domain-specific satisfaction with life. These findings suggest that compensatory secondary control can be an adaptive way of mastering a demand when primary control is not possible

Predicting substance use behavior among South African adolescents: The role of leisure experiences across time

Using seven waves of data, collected twice a year from the 8th through the 11th grades in a low-resource community in Cape Town, South Africa, we aimed to describe the developmental trends in three specific leisure experiences (leisure boredom, new leisure interests, and healthy leisure) and substance use (cigarettes, alcohol, and marijuana) behaviors and to investigate the ways in which changes in leisure experiences predict changes in substance use behaviors over time. Results indicated that adolescents’ substance use increased significantly across adolescence, but that leisure experiences remained fairly stable over time. We also found that adolescent leisure experiences predicted baseline substance use and that changes in leisure experiences predicted changes in substance use behaviors over time, with leisure boredom emerging as the most consistent and strongest predictor of alcohol, cigarette, and marijuana use. Implications for interventions that target time use and leisure experiences are discussed.Web of Scienc

The Interaction Between Pubertal Timing and Peer Popularity for Boys and Girls: An Integration of Biological and Interpersonal Perspectives on Adolescent Depression

The transition to adolescence marks a time of sharply increased vulnerability to the development of depression, particularly among girls. Past research has examined isolated risk factors from individual theoretical models (e.g., biological, interpersonal, and cognitive) of depression, but few have examined integrative models. This study investigated the conjoint effects of early pubertal timing and popularity in the longitudinal prediction of depressive symptoms. A total of 319 girls and 294 boys (ages 11–14) provided information on their pubertal status, depressive symptoms, and the social status (i.e., popularity) of their peers. Adolescents completed a second measure of depressive symptoms 11 months after the initial time point. Findings supported an integrated biological-interpersonal model in explaining the development of depressive symptoms during adolescence. Early pubertal development was associated with increase in depressive symptoms only when accompanied by low levels of popularity. High levels of popularity buffered the association between early pubertal development and later depressive symptoms. Unexpectedly, these results were significant both for girls and boys. Results are discussed in terms of dynamic systems theories

In Vitro and In Vivo Efficacy of Monepantel (AAD 1566) against Laboratory Models of Human Intestinal Nematode Infections

Soil-transmitted helminthiases affect more than one billion people among the most vulnerable populations in developing countries. Currently, control of these infections primarily relies on chemotherapy. Only five drugs are available, all of which have been in use for decades. None of the drugs are efficacious using single doses against all soil-transmitted helminths (STH) species and show low efficacy observed against Trichuris trichiura. In addition, the limited availability of current drug treatments poses a precarious situation should drug resistance occur. Therefore, there is great interest to develop novel drugs against infections with STH. Monepantel, which belongs to a new class of veterinary anthelmintics, the amino-acetonitrile derivatives, might be a potential drug candidate in humans. It has been extensively tested against livestock nematodes, and was found highly efficacious and safe for animals. Here we describe the in vitro and in vivo effect of monepantel, on Ancylostoma ceylanicum, Necator americanus, Trichuris muris, Strongyloides ratti, and Ascaris suum, five parasite-rodent models of relevance to human STH. Since we observed that monepantel showed only high activity on one of the hookworm species and lacked activity on the other parasites tested we cannot recommend the drug as a development candidate for human soil-transmitted helminthiases

The role of psychologists in international migration research: complementing other expertise and an interdisciplinary way forward

This research note addresses the current and potential future role of psychologists in the study of international migration. It reviews ways in which psychologists have contributed to the study of migration, as well as ways in which psychological scholarship could be integrated with work from other social science fields. Broadly, the note discusses four major contributions that psychology brings to the study of international migration—studying migrants’ internal psychological experiences, incorporating a developmental perspective, conducting experimental studies, and integrating across levels of analysis. Given the position of psychology as a ‘hub science’ connecting more traditional social sciences with health and medical sciences, we argue for a more prominent role for psychologists within the study of international migration. Such a role is intended to complement the roles of other social scientists and to create a more interdisciplinary way forward for the field of migration studies. The research note concludes with an agenda for further scholarship on migration.Development Psychopathology in context: clinical setting