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Because all aspects of social life have a mental component, sociology’s focus is not society alone but mind and society. Insofar as mind is an emergent level of brainwork, the description and measurement of mindwork amidst social interaction can be accomplished by neurometric measurement methodology. The authors’ topic, hyperscanning, involves the simultaneous recording of either hemodynamic or neuroelectric measurement of brain activity in two (or more) interacting individuals. The authors consider two hyperscanning methods, functional magnetic resonance imaging and electroencephalography (EEG). Although functional magnetic resonance imaging provides excellent spatial resolution of brain-region activation, the temporal resolution of EEG is unmatched. EEG’s low spatial resolution has been overcome by low-resolution electromagnetic tomography. Hyperscanning studies show that interpersonal coordination of action includes mutual entrainment or synchronization of neural dynamics, flow of information between brains, and causal effects of one brain upon another with respect to social-signaling processes involving fairness, reciprocity, trust, competition, cooperation, and leadership.

Background Dental caries affects billions worldwide and in the U.S. is among the most prevalent noncommunicable diseases in both children and adults. Early in the caries process, it can be arrested by dental sealants, which are non-invasive and thus tooth sparing, however, few dentists have adopted this approach. Deliberative engagement processes enable participants to engage with diverse perspectives on a policy issue and develop and share with policy makers informed opinions about the policy issue. We examined the effects of a deliberative engagement process on the ability of oral health providers to endorse implementation interventions and to apply dental sealants. Methods Using a stepped wedge design, 16 dental clinics were cluster randomized, and 680 providers and staff were exposed to a deliberative engagement process that included an introductory session, workbook, facilitated small group deliberative forum, and post-forum survey. Forum participants were assigned to forums to ensure diverse role representation. Mechanisms of action examined included sharing voice and diversity of opinion. Three months after each clinic’s forum, the clinic manager was interviewed about implementation interventions deployed. There were 98 clinic-months in the non-intervention period and 101 clinic-months in the intervention period. Results Compared with providers and staff in small clinics, providers and staff in medium and large clinics more strongly agreed that their clinic should adopt two of the three proposed implementation interventions targeting the first barrier and one of the two proposed implementation interventions targeting the second barrier. Compared with the non-intervention period, in the intervention period providers did not place more sealants on occlusal non-cavitated carious lesions. Survey respondents reported sharing both promotive and prohibitive voice. From the beginning to the end of the forums, most forum participants did not change their opinions about the possible implementation interventions. At the end of the forums, there was no significant within-group variability in implementation interventions endorsed. Conclusions Deliberative engagement intervention may help clinic leadership identify implementation interventions when there is a challenging problem, a network of semi-autonomous clinics, and autonomous providers within those clinics. It remains to be determined whether there is a range of perspectives within clinics. Trial Registration: This project is registered at ClinicalTrials.gov with ID NCT04682730. The trial was first registered on 12/18/2020. https://clinicaltrials.gov/ct2/show/NCT04682730

Lymphoid tissue inducer (LTi) cells are required for lymph node formation during fetal development, and recent evidence implies a role in mucosal immunity in the adult. LTi cells share some phenotypic features of conventional natural killer (NK; cNK) cells; however, little is known to date about the relationship between these two cell types. We show that lineage(-) (Lin(-)) CD127(+)RORC(+) LTi-like cells in human tonsil are precursors to CD56(+)CD127(+)RORC(+)NKp46(+) cells, which together comprise a stable RORC(+) lineage. We find that LTi-like cells and their CD56(+) progeny can be expanded and cloned ex vivo without loss of function and without conversion into cNK cells. Clonal analysis reveals heterogeneity of cytokine production within the CD127(+) LTi-like population. Furthermore, we identify within the tonsil a cNK precursor population that is characterized as Lin(-)CD117(+)CD161(+)CD127(-) cells. Overall, we propose that CD127(+)RORC(+) cells, although they share some characteristics with cNK cells, represent a functionally and developmentally distinct lineage

A growing body of evidence indicates that interactions between neoplastic cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) are crucial in promoting tumor cell invasion and progression. Macrophages have an ambiguous role in these processes as this M1 phenotype correlates with tumoricidal capacity, whereas TAMs of M2 phenotype exert tumor-promoting effects. In this study, we provide evidence that interactions between mouse breast tumor cells and TAMs remodel the TME, leading to the upregulation of Fra-1, a member of the FOS family of transcription factor. In turn, this proto-oncogene initiates activation of the IL-6/JAK/Stat3 signaling pathway. This creates a malignant switch in breast tumor cells, leading to increased release of proangiogenic factors MMP-9, vascular endothelial growth factor and transforming growth factor-beta from tumor cells and intensified invasion and progression of breast cancer. Proof of the concept for the crucial role played by transcription factor Fra-1 in regulating these processes was established by specific knockdown of Fra-1 with small interfering RNA, which resulted in a marked suppression of tumor cell invasion, angiogenesis and metastasis in a mouse breast cancer model. Such a strategy could eventually lead to future efficacious treatments of metastatic breast cancer.

Objective—Similarities between neovascular ingrowth in atherosclerotic plaques and angiogenesis in tumors suggest that antiangiogenic factors that target tumor expansion may prove efficacious in the treatment of atherosclerosis. This study examined whether an oral DNA vaccine against the murine VEGF receptor 2 (Flk-1) with demonstrated antitumor effect through inhibition of pathological neovascularization can prevent or retard progression of atherosclerosis in hyperlipidemic low density lipoprotein receptor–deficient (LDLr−/−) mice.Methods and Results—Vaccination against Flk-1 resulted in T cell activation, suppression of neoangiogenesis, and a marked reduction in atherosclerosis which was independent of hypercholesterolemia in both male and female mice. Immunohistochemical characterization of aortic sinus lesions showed that the decreased lesion area was not associated with reduced plaque stability and had a lower density of microvessels.Conclusions—These findings demonstrate for the first time that a DNA vaccine targeting activated endothelial cells in atherosclerotic lesions provides direct atheroprotective effects.

Recently, the cancer stem cell hypothesis has gained significant recognition as the descriptor of tumorigenesis. Although previous studies relied on transplanting human or rat tumor cells into immunecompromised mice, our study used the Hoechst 33342 dye–based side population (SP) technique to isolate and transplant stem cell–like cancer cells (SCLCCs) from the 4T1 and NXS2 murine carcinoma cell lines into the immune-competent microenvironment of syngeneic mice. 4T1 cells displayed an SP of 2% with a Sca-1highc-Kit–CD45– phenotype, whereas NXS2 cells contained an SP of 0.2% with a Sca-1highCD24highc-Kit–CD45–GD high2 phenotype. Reverse transcription–polymerase chain reaction (RT-PCR) further revealed up-regulation in SP cells of ABCG2, Sca-1, Wnt-1, and TGF-β2. Additionally, 4T1 and NXS2 SP cells exhibited increased resistance to chemotherapy, and 4T1 SP cells also showed an increased ability to efflux doxorubicin, which correlated with a selective increase in the percentage of SP cells found in the tumors of doxorubicin-treated mice. Most importantly, SP cells showed a markedly higher repopulation and tumorigenic potential in vivo, which correlated with an increased number of cells in the SP compartment of SP-derived tumors. Taken together, these results show that we successfully characterized SCLCCs from 2 murine carcinoma cell lines in the immune-competent microenvironment of syngeneic mice.

The NKG2D receptor is a stimulatory receptor expressed on NK cells and activated CD8 T cells. We previously demonstrated that engaging the NKG2D receptor markedly improved the efficacy of a survivin-based DNA vaccine. The combination vaccine, encoding both the NKG2D ligand H60 and survivin, activates innate and adaptive antitumor immunity and results in better protection against tumors of different origin and NKG2D expression levels. Here we demonstrate that the enhanced vaccine efficacy is in part attributable to increased cross talk between lymphocytes. Depletion of CD8 T cells during priming reduces the vaccine-induced activation of dendritic cells (DCs) and NK cell activity. Depletion of NK cells during priming leads to reduced DC activation and CTL activity. However, depletion of CD4 T cells results in the activation of DCs, NK cells, and CD8 T cells and enhances NK cell activity. The pH60/Survivin vaccine also increases DCs and NK cells but decreases CD4 T cell homing to Peyer patches, presumably as a result of changes in the homing receptor profile. Thus, by preferentially activating and attracting positive regulators and reducing negative regulators in Peyer patches, this dual-function DNA vaccine induces a microenvironment more suitable for NK cell activation and T cell priming.

FcgammaRs are specialized cell surface receptors that coordinately regulate immune responses. Although FcgammaR expression is a prerequisite for the development of several immune complex-mediated diseases, the mechanism responsible for FcgammaR-dependent regulation in autoimmunity remains unclear. Therefore, we assessed FcgammaR-dependent regulation of inflammation in proteoglycan-induced arthritis (PGIA) using FcgammaR(-/-) mice. FcgammaRIIb(-/-) mice developed arthritis at an earlier time point and with a greater severity than wild-type (WT) mice. In gamma-chain(-/-) (FcgammaRI(-/-) and FcgammaRIII(-/-)) mice, no clinical or histological evidence of inflammation was observed. Exacerbation of arthritis in FcgammaRIIb(-/-) mice correlated with enhanced PG-specific Ab production, but did not significantly affect PG-specific T cell priming. In gamma-chain(-/-) mice, the absence of arthritis did not correlate with serum Ab responses, as PG-specific Ab production was normal. Although PG-specific T cell proliferation was diminished, spleen cells from gamma-chain(-/-) mice successfully adoptively transferred arthritis into SCID mice. Our studies indicated that the mechanism responsible for FcgammaR regulation of PGIA development was at the level of inflammatory cytokine and beta-chemokine expression within the joint. FcgammaRIIb regulated the development of PGIA by controlling the initiation of cytokine and chemokine expression within the joint before the onset of arthritis, whereas the expression of FcgammaRI and or FcgammaRIII controlled cytokine and chemokine expression late in the development of PGIA during the onset of disease. These results suggest that FcgammaRs are critical for the development of inflammation during PGIA, possibly by maintaining or enhancing inflammatory cytokine and beta-chemokine production.

This article focuses on the similarities and relations between the European therapeutic community for children and adults on the one hand and the American drug-free “concept” therapeutic community on the other. Both approaches are reviewed in a historical and comparative perspective with special attention to several critical issues: democracy versus hierarchy, self-help versus professionalism, psychoanalysis versus behaviorism and concept versus social learning. These two different TC-approaches can be considered as subdivisions of one modality, namely an environment for social learning in which living together in a group can be regarded as the primary agent of growth and human development. In recent years there has been a tendency towards further integration of these two approaches.

AUTHORS' NOTE: The authors are indebted to a large number of people in both the Netherlands and the United States who took the time to read and comment on drafts of this paper. Simon Stack provided continual editorial input. Dr. Adriaan C. M. Jansen of the University of Amsterdam, Bert Bieleman of Intraval, Groningen-Rotterdam, and Hans Dupont of the International Institute for Psycho-Social and Socio-Ecological Research in Maastricht provided invaluable insight and comments on the Dutch situation. In the United States, Dr. Bruce Johnson of National Development and Research Institutes, Inc., and Dr. Charles Winick of the Graduate Center of the City University of New York were sources of valuable criticism and discussion. Please address comments or reprint requests to: Stephen J. Sifaneck, National Development and Research Institutes, 1I Beach St., New York 10013.

The term 'stimulant' refers to a class of drugs that increase psychophysiological arousal. From the viewpoint of prevention, it is more useful to look primarily at the social consequences and functions of stimulants. Every society has a documented use of stimulants. When planning interventions the dynamics of use must be placed in the foreground. Stimulant epidemics, like problematic stimulant users, have a natural tendency to burn themselves out. Different types of stimulants may differ in their origins, but their epidemiological consequences and use functions tend to be similar. Implications for prevention can be drawn from the characteristics of stimulant use epidemics. Users at risk for socially unacceptable patterns should be targeted for prevention efforts. Mass media campaigns that single out stimulants should be avoided. Much of the harm associated with stimulants is a consequence of life-styles characterized by polydrug use and unhealthy practices. Prevention should be timed to the appropriate period of the epidemic. Interventions useful at period 1 will not work at period 2. The recommendations of the WHO Advisory Group on the Adverse Effects of Cocaine and Coca provide a good model for primary, secondary and tertiary prevention for all forms of stimulant misuse. Stimulant prevention must be creative in finding ways of encouraging the movements of the drug to the periphery of users' lives.

In Dutch samples of treated heroin addicts, high prevalences of a heterogenous psychiatric co-morbidity can be found with regard to Diagnostic and Statistical Manual (third edition) ( DSM-III ) classifications, Zung Depression Inventory, and sum scores of a 90-item Symptom Checklist (SCL-90). A high-threshold (N = 87) and a low-threshold (N = 116) program are compared with regard to psychopathology and severity of psychopathology. A consecutive admissions design was used. More than 50% of the respondents suffered from a lifetime DSM-III Axis I disorder (70% with antisocial personality disorder included), and 40% were still suffering from one of the disorders in the year preceding the interview. Schizophrenia was diagnosed five times as much as in normal population samples (5%). The most frequently diagnosed disorders were recurrent major depression, phobic disorders, alcohol abuse and dependence, dysthymic disorder, and antisocial personality disorder. The prevalences of DSM-III disorders, the total number of symptoms, and the score on the Zung Depression Inventory and 90-item Symptom Checklist were all significantly higher in treatment-seeking drug addicts entering the high-threshold program. Within each program, three clinically meaningful subgroups can be distinguished: one group with DSM-III Axis I lifetime or current psychopathology and/or antisocial personality disorder, one with antisocial personality disorder only, and one with neither DSM-III psychopathology nor antisocial personality disorder. Possibly, self-selection results in patients with more serious conditions entering more treatment-oriented facilities. Odds ratios show that schizophrenia and mood disorders and especially associated on a lifetime and current basis.

Needle exchange is a practical and important part of the Dutch prevention strategy to check the spread of HIV among injecting drug users (IDUs). However, needle-exchange programs are often tied to drug treatment programs that only reach a limited number of IDUs. To overcome this limitation, alternative designs are considered and initiated. This article describes a community-based approach to needle exchange that is built on empowerment of, and intense participation by, known IDUs to target unknown IDUs for delivery of clean needles. The needle-exchange patterns of the IDUs participating in this collective scheme are compared to those of other users who exchanged needles on an individual basis. It was found that this approach extended the reach of the program to a great degree and that it was well received in the IDU community. However, the results were negatively influenced by police activities aimed at closing down places where drugs were used and sold. It is concluded that engaging IDUs in peer-group-directed prevention efforts is both feasible and promising.

Lymphoid tissue inducer cells are members of an emerging family of innate lymphoid cells (ILC). Although these cells were originally reported to produce cytokines such as interleukin-17 (IL-17) and IL-22, we demonstrate here that human CD127(+)RORC(+) and CD56(+)CD127(+) LTi-like ILC also express IL-2, IL-5, and IL-13 after activation with physiologic stimuli such as common gamma-chain cytokines, Toll-like receptor (TLR) 2 ligands, or IL-23. Whereas TLR2 signaling induced IL-5, IL-13, and IL-22 expression in a nuclear factor kappa B (NF-kappa B)-dependent manner, IL-23 costimulation induced only IL-22 production. CD127(+) LTi-like ILC displayed clonal heterogeneity for IL-13 and IL-5 production, suggesting in vivo polarization. Finally, we identified a role for autocrine IL-2 signaling in mediating the effects of TLR2 stimulation on CD56(+)CD127(+) and CD127(+) LTi-like ILC. These results indicate that human LTi-like ILC can directly sense bacterial components and unravel a previously unrecognized functional heterogeneity among this important population of innate lymphoid cells

Interleukin 22 (IL-22) is a member of the IL-10 cytokine family that is involved in inflammatory and wound healing processes. Originally considered a T helper type 1 (T(H)1)-associated cytokine, IL-22 has since been shown to be produced mainly by IL-17-producing helper T cells (T(H)-17 cells). Here we describe a previously uncharacterized IL-22-producing human helper T cell population that coexpressed the chemokine receptor CCR6 and the skin-homing receptors CCR4 and CCR10. These cells were distinct from both T(H)-17 cells and T(H)1 cells. Downregulation of either the aryl hydrocarbon receptor (AHR) or the transcription factor RORC by RNA-mediated interference affected IL-22 production, whereas IL-17 production was affected only by downregulation of RORC by RNA-mediated interference. AHR agonists substantially altered the balance of IL-22- versus IL-17-producing cells. This subset of IL-22-producing cells may be important in skin homeostasis and pathology.

Recently the use patterns, circumstances and consequences of cocaine have become of interest to both researchers and policy makers in Europe. Currently only a few studies have been conducted of the social epidemiology of cocaine. In this article, focus is placed upon the use of cocaine in one subpopulation, heroin addicts. Based mainly upon ethnographic research conducted in the city of Rotterdam it can be estimated that the prevalence of cocaine use in this population has reached a very high level. The mode of ingesting cocaine parallels that of heroin; Injecting Drug Users inject cocaine-hydrochloride, heroin smokers smoke cocaine base. This cocaine base is mainly processed by users themselves. An exception to this rule of self-processing can be found in the most marginalized addicts who do not have access to the house addresses where both heroin and cocaine-hydrochloride are sold. In this group the selling of 'cooked cocaine', a crack-like product, has occurred. The circumstances and potential consequences of the emergence of 'cooked cocaine' are discussed.

Medical and public opinion about cocaine use have shifted dramatically over the past decade. New research methodologies and definitions to evaluate the impact of cocaine are needed. This paper presents a theoretical definition and empirical analysis of the 'casual user' of cocaine. Data have been drawn from a subsample of 58 cocaine users and their cocaine-using contacts in Rotterdam. The methodology of the study presents a novel approach to patterns of cocaine use involving the integration of social network variables with 'snowball' sampling data collection techniques. The theoretical definition is systematically related to two social context variables: (1) the scope of settings where contacts use cocaine; (2) the degree of involvement in social network relations of actual cocaine use. Scope of settings has been defined in terms of the number of cocaine-using social circuits contacts are drawn from: i.e. 'narrow' setting where all contacts originate from one circuit while a 'wide' setting indicates contacts come from two or more circuits. Involvement has been defined in terms of the percentage of contacts where the relation with study participants is characterized by cocaine use most or all of the time. Additional social network variables measuring the mean duration (in years) of contacts' cocaine use and the use of cocaine with contacts in the last six months are subsequently related to the scope and involvement variables. The implications of the analysis for a new cross-classification of cocaine use patterns are discussed with special reference to public health policy issues.

Aim of the study Ibogaine is a naturally occurring psychoactive indole alkaloid that is used to treat substance-related disorders in a global medical subculture, and is of interest as an ethnopharmacological prototype for experimental investigation and possible rational pharmaceutical development. The subculture is also significant for risks due to the lack of clinical and pharmaceutical standards. This study describes the ibogaine medical subculture and presents quantitative data regarding treatment and the purpose for which individuals have taken ibogaine. Materials and methods All identified ibogaine “scenes” (defined as a provider in an associated setting) apart from the Bwiti religion in Africa were studied with intensive interviewing, review of the grey literature including the Internet, and the systematic collection of quantitative data. Results Analysis of ethnographic data yielded a typology of ibogaine scenes, “medical model”, “lay provider/treatment guide”, “activist/self-help”, and “religious/spiritual”. An estimated 3414 individuals had taken ibogaine as of February 2006, a fourfold increase relative to 5 years earlier, with 68% of the total having taken it for the treatment of a substance-related disorder, and 53% specifically for opioid withdrawal. Conclusions Opioid withdrawal is the most common reason for which individuals took ibogaine. The focus on opioid withdrawal in the ibogaine subculture distinguishes ibogaine from other agents commonly termed “psychedelics”, and is consistent with experimental research and case series evidence indicating a significant pharmacologically mediated effect of ibogaine in opioid withdrawal.

Over the past several years it has become apparent that the tumor stroma represents a significant target for anti-cancer therapies. Therefore we evaluated the strategy of targeting the tumor stroma with a novel DNA vaccine encoding murine platelet derived growth factor receptor-beta (mPDGFRbeta). Immunization with this vaccine induced cytotoxic lysis of mPDGFRbeta-expressing target cells and protected mice from the growth and dissemination of murine colon, breast and lung carcinoma. Furthermore, this novel vaccine suppresses angiogenesis in vivo and reduces the numbers of tumor-associated, mPDGFRbeta-expressing pericytes as suggested by a decrease in intra-tumoral expression of mPDGFRbeta and NG2.

Endoglin (CD105), a co-receptor in the TGF-beta receptor complex, is over-expressed on proliferating endothelial cells in the breast tumor neovasculature and thus offers an attractive target for anti-angiogenic therapy. Here we report the anti-angiogenic/anti-tumor effects achieved in a prophylactic setting with an oral DNA vaccine encoding murine endoglin, carried by double attenuated Salmonella typhimurium (dam-, AroA-) to a secondary lymphoid organ, i.e., Peyer's patches . We demonstrate that an endoglin vaccine elicited activation of antigen-presenting dendritic cells, coupled with immune responses mediated by CD8+ T cells against endoglin-positive target cells. Moreover, we observed suppression of angiogenesis only in mice administered with the endoglin vaccine as compared to controls. These data suggest that a CD8+ T cell-mediated immune response induced by this vaccine effectively suppressed dissemination of pulmonary metastases of D2F2 breast carcinoma cells presumably by eliminating proliferating endothelial cells in the tumor vasculature. It is anticipated that vaccine strategies such as this may contribute to future therapies for breast cancer.

Tumor-associated macrophages (TAMs) are associated with tumor progression and metastasis. Here, we demonstrate for the first time that legumain, a member of the asparaginyl endopeptidase family functioning as a stress protein, overexpressed by TAMs, provides an ideal target molecule. In fact, a legumain-based DNA vaccine served as a tool to prove this point, as it induced a robust CD8+ T cell response against TAMs, which dramatically reduced their density in tumor tissues and resulted in a marked decrease in proangiogenic factors released by TAMs such as TGF-beta, TNF-alpha, MMP-9, and VEGF. This, in turn, led to a suppression of both tumor angiogenesis and tumor growth and metastasis. Importantly, the success of this strategy was demonstrated in murine models of metastatic breast, colon, and non-small cell lung cancers, where 75% of vaccinated mice survived lethal tumor cell challenges and 62% were completely free of metastases. In conclusion, decreasing the number of TAMs in the tumor stroma effectively altered the tumor microenvironment involved in tumor angiogenesis and progression to markedly suppress tumor growth and metastasis. Gaining better insights into the mechanisms required for an effective intervention in tumor growth and metastasis may ultimately lead to new therapeutic targets and better anticancer strategies.

The interaction of NKG2D, a stimulatory receptor expressed on natural killer (NK) cells and activated CD8+T cells, and its ligands mediates stimulatory and costimulatory signals to these cells. Here, we demonstrate that DNA-based vaccines, encoding syngeneic or allogeneic NKG2D ligands together with tumor antigens such as survivin or carcinoembryonic antigen, markedly activate both innate and adaptive antitumor immunity. Such vaccines result in highly effective, NK- and CD8+T cell-mediated protection against either breast or colon carcinoma cells in prophylactic and therapeutic settings. Notably, this protection was irrespective of the NKG2D ligand expression level of the tumor cells. Hence, this strategy has the potential to lead to widely applicable and possibly clinically useful DNA-based cancer vaccines.

Inflammatory joint diseases such as rheumatoid arthritis tend to destroy joint cartilage and bone matrices. Since bone resorption is a common characteristic of rheumatoid arthritis, one of the cell types thought to play a vital role in the destruction of these matrices are the osteoclasts. Osteoclasts and osteoclastogenic factors such as inflammatory cytokines and RANK-L are present within inflamed joints, and osteoclastic bone resorptive activities are also displayed, further suggesting the possibility that osteoclasts are responsible for the joint cartilage and bone matrix damage observed in this joint disease.

Street children are a high priority for health policy and service planning in Kenya. Poverty, wars, famine and disease have resulted in street children having a persistent presence in African cities and towns. The Maastricht Social Network Analysis (MSNA) was implemented as the core instrument in a battery to measure the health status of the street children. Owing to the absence of census data of street children in Kenya and the difficulty in tracking this mobile population, we implemented a mixed snowball and convenience sampling design to recruit research subjects. Three hundred street and orphanage children, and 100 primary school children as a control group, were included in the study. The MSNA provided a social diagnosis that complements the clinical diagnosis of the health status of the sample. Only one main methodological question is presented: is the MSNA applicable to describe the personal social networks of (1). children and of (2). people living in a Kenyan culture? Qualitative field observations, key informant interviews and focus groups inform the adaptation of the MSNA instrument, and improve its face validity. A case series analysis is presented. The main result is that the street children population consists of distinct subgroups defined by the UNICEF classification as 'on' and 'of' the street and by gender. Street children networks have some notable deficiencies depending on the subgroup. Constant across the groups is the deficiency of service providers in their networks. The conclusion is that the MSNA is a suitable instrument for obtaining a social diagnosis and gathering other useful information that helps in understanding the social and health backgrounds, status and daily experiences of Kenyan scavenging street children. Applying the MSNA protocol was successful in the diagnosis and interpretation of the findings.

IL-4, a well-recognized modulator of macrophage activation, is perceived as an anti-inflammatory cytokine; however, under certain circumstances IL-4 may function as a proinflammatory cytokine. We have previously demonstrated that IL-4 treatment of mice with proteoglycan-induced arthritis (PGIA) inhibited the development of disease. To determine whether the capacity of IL-4 to inhibit disease is dependent on IL-4-mediated regulation of IL-12, we assessed the requirement for IL-4 in modulating development of PGIA. Immunization of mice, lacking IL-4 and Stat6, with proteoglycan results in a significant increase in arthritis severity in comparison to wild-type controls, suggesting that arthritis severity is regulated by IL-4 through a Stat6-dependent mechanism. Concomitant with exacerbated disease in IL-4−/− mice, there is a significant increase in the systemic production of proinflammatory cytokines IL-12, TNF-α, and IFN-γ and in levels of mRNA transcripts for proinflammatory cytokines and chemokines in joints. Disease is suppressed in Stat4−/− mice indicating that elevated levels of IL-12 contribute to exacerbation of arthritis and that suppression is accompanied by reduced levels of IFN-γ production. In support of this, IFN-γ−/− mice are protected from PGIA and the degree of inflammation is similar to Stat4−/− mice. The decrease in disease severity in IFN-γ−/− and Stat4−/− mice correlates with diminished TNF-α levels but there is no switch to a Th2-type response. Taken together, these results suggest that IL-4 regulates the severity of disease in PGIA by controlling IL-12 production, which in turn regulates the magnitude of IFN-γ expression through a Stat4-dependent pathway.

The relation between knowledge about memory capacity, delayed recall on a 15-word-list task, and sociological lifestyle variables was examined in a sample of 1,398 adults ranging in age between 25 and 82. Participants were sampled fi-om a registration network of family medical practices representing the general population of the south of The Netherlands. Participants were stratified for age, sex, and level of occupational achievement. We found that lifestyle opportunity structure as indicated by social network characteristics and lifestyle conduct as indicated by activity scores were related positively to the dependent variables of memory knowledge and delayed recall. Study results showed that participants with better delayed recall scores had larger social networks, were younger, were more frequently female, had more years of education, and were less externally oriented. Participants with higher metamemory capacity scores had more frequent contacts in their social network, considered themselves more frequently an active person, were younger, were female, reported fewer health complaints, and had a higher internal locus of control. Delayed recall scores did not predict metamemory capacity scores after we controlled for other variables. The results support the conclusion that cognitive performance is influenced significantly by lifestyle components.

Considerable evidence has accumulated to suggest that intracerebroventricular administration of enkephalinase inhibitors, which do not penetrate the blood-brain barrier, significantly attenuates opioid withdrawal syndrome. Therefore, the aim of this study was to examine the effect of intraperitoneal (i.p.) administration of orally active enkephalinase inhibitors, acetorphan (2.5-20 mg kg-1) and SCH 34826 (15-120 mg kg-1). These drugs significantly decreased the severity of the naloxone precipitated withdrawal syndrome in morphine dependent rats and mice. It therefore appears that these orally active enkephalinase inhibitors are promising tools in studying modulation of opioid dependence phenomena.

Epidemiological data on HIV seroprevalence has been essential in assessing the (future) extent of the AIDS epidemic. By coupling these data with quantifiable variables related to injection drug use (frequency of injecting, number of needle sharing partners) specific 'risk behaviors' could be determined, accounting for the rapid spread of the virus in the injecting drug user (IDU) population. Yet, such data give little information on the social mechanisms and setting generating such risk behaviors. In order to understand the transmission of HIV among the IDU population one needs to study the micro settings and social context of drug use. This paper describes and explores certain patterns of drug use, sharing, and natural support systems found amongst IDUs in two very different cities, Rotterdam (The Netherlands) and the Bronx, New York City (USA). By specifying details of the micro-settings of everyday drug use in both locales, it is possible to identify certain common elements and consequences of personal and social behavior driven by drug use per se (e.g. drug preference), and to differentiate these from behaviors and consequences determined by drug policy and the social context in which drug use actually occurs. These policies and the social context they create can in turn be shown to relate to risks for HIV transmission, e.g. the increased likelihood of sharing injection equipment. A more careful ethnographic approach, taking advantage of natural experimental opportunities, comparisons and controls, may be utilized to examine drug-related behaviors in their social context and to better assess their relevance to public health--especially to AIDS.

This paper discusses what works and what does not work in drug abuse epidemiology in Europe. Given the tradition in European countries of defining the drug abuse problem in terms of social and medical interventions, epidemiological research is also tied to these interventions, and consequently to community-based research. What seems not to work, and what is generally suspect are grand legal designs to solve the drug problem. Promising initiatives are going towards a compromise between a relaxation of legal sanctions but a tendency away from legalization. What is recommended is striving towards a more analytic and multidisciplinary epidemiology that can help society critically evaluate the truth-value of its moral prerogatives.

IL-10 is a potent immunoregulatory cytokine attenuating a wide range of immune effector and inflammatory responses. In the present study, we assess whether endogenous levels of IL-10 function to regulate the incidence and severity of collagen-induced arthritis. DBA/1 wildtype (WT), heterozygous (IL-10+/-) and homozygous (IL-10-/-) IL-10-deficient mice were immunized with type II collagen. Development of arthritis was monitored over time, and collagen-specific cytokine production and anticollagen antibodies were assessed. Arthritis developed progressively in mice immunized with collagen, and 100% of the WT, IL-10+/-, and IL-10-/- mice were arthritic at 35 days. However, the severity of arthritis in the IL-10-/- mice was significantly greater than that in WT or IL-1+/- animals. Disease severity was associated with reduced IFN-γ levels and a dramatic increase in CD11b-positive macrophages. Paradoxically, both the IgG1 and IgG2a anticollagen antibody responses were also significantly reduced. These data demonstrate that IL-10 is capable of controlling disease severity through a mechanism that involves IFN-γ. Since IL-10 levels are elevated in rheumatoid arthritis synovial fluid, these findings may have relevance to rheumatoid arthritis.

BALB/c mice immunized with human cartilage proteoglycan (PG) develop arthritis accompanied by the production of autoantibodies to mouse cartilage PG. To determine whether the autoantibody isotype contributes to the onset and severity of arthritis, PG-specific serum IgG1 (Th2, IL-4-cytokine-supporting) and IgG2a (Th1, IFN-γ-controlling) concentrations were monitored during immunization with PG in IL-4-deficient and IFN-γ-deficient mice. Paradoxically, despite elevated IFN-γ, the PG-specific IgG1 isotype was significantly higher than the PG-specific IgG2a response, and the PG-specific IgG1 isotype was independent of IL-4. In contrast, the serum concentration of PG-specific IgG2a isotype was six times higher in IL-4-deficient mice than in wild-type controls. Moreover, the high concentration of PG-specific IgG2a isotype in IL-4-deficient mice corresponded to an increased severity of arthritis. The concentration of PG-specific IgG2a isotype was lower in IFN-γ-deficient mice than in wild-type mice, and the incidence and severity of arthritis also were significantly lower. Concentrations of PG-specific IgG2a isotype autoantibody correlated with the onset and severity of arthritis, suggesting a pathological role of this isotype, probably locally in the joint.

This article presents a human model of creativity and the drug experience to complement animal models and to contribute to an understanding of the significant role drug experience can play for the neurosciences. Several hypotheses concerning cerebral functioning at the different phases of the drug career are developed, and a call for research is made following an experimental protocol. The exploration of these hypotheses would be of general interest for providing better insight into the control mechanisms determining the delicate process of creating functional forms that link words to feelings.