Striatal adenosine A2A receptor involvement in normal and large nest building deer mice: Perspectives on compulsivity and anxiety.

Obsessive-compulsive disorder (OCD) is characterized by recurring obsessive thoughts and repetitive behaviors that are often associated with anxiety and perturbations in cortico-striatal signaling. Given the suboptimal response of OCD to current serotonergic interventions, there is a need to better understand the psychobiological mechanisms that may underlie the disorder. In this regard, investigations into adenosinergic processes might be fruitful. Indeed, adenosine modulates both anxiety- and motor behavioral output. Thus, we aimed to explore the potential associations between compulsive-like large nest building (LNB) behavior in deer mice, anxiety and adenosinergic processes. From an initial pool of 120 adult deer mice, 34 normal nest building (NNB)- and 32 LNB-expressing mice of both sexes were selected and exposed to either a normal water (wCTRL) or vehicle control (vCTRL), lorazepam (LOR) or istradefylline (ISTRA) for 7- (LOR) or 28 days after which nesting assessment was repeated and animals screened for anxiety-like behavior in an anxiogenic open field. Mice were then euthanized, the striatal tissue removed on ice and the adenosine A2A receptor expression quantified. Our findings indicate that NNB and LNB behavior are not distinctly associated with measures of generalized anxiety and that ISTRA-induced changes in nesting expression are dissociated from changes in anxiety scores. Further, data from this investigation show that nesting in deer mice is directly related to striatal adenosine signaling, and that LNB is founded upon a lower degree of adenosinergic A2A stimulation.

Rox8 promotes microRNA-dependent yki messenger RNA decay.

The Hippo pathway is an evolutionarily conserved regulator of organ growth and tumorigenesis. In Drosophila, oncogenic RasV12 cooperates with loss-of-cell polarity to promote Hippo pathway-dependent tumor growth. To identify additional factors that modulate this signaling, we performed a genetic screen utilizing the Drosophila RasV12/lgl-/- in vivo tumor model and identified Rox8, a RNA-binding protein (RBP), as a positive regulator of the Hippo pathway. We found that Rox8 overexpression suppresses whereas Rox8 depletion potentiates Hippo-dependent tissue overgrowth, accompanied by altered Yki protein level and target gene expression. Mechanistically, Rox8 directly binds to a target site located in the yki 3' UTR, recruits and stabilizes the targeting of miR-8-loaded RISC, which accelerates the decay of yki messenger RNA (mRNA). Moreover, TIAR, the human ortholog of Rox8, is able to promote the degradation of yki mRNA when introduced into Drosophila and destabilizes YAP mRNA in human cells. Thus, our study provides in vivo evidence that the Hippo pathway is posttranscriptionally regulated by the collaborative action of RBP and microRNA (miRNA), which may provide an approach for modulating Hippo pathway-mediated tumorigenesis.

A LATS biosensor screen identifies VEGFR as a regulator of the Hippo pathway in angiogenesis.

The Hippo pathway is a central regulator of tissue development and homeostasis, and has been reported to have a role during vascular development. Here we develop a bioluminescence-based biosensor that monitors the activity of the Hippo core component LATS kinase. Using this biosensor and a library of small molecule kinase inhibitors, we perform a screen for kinases modulating LATS activity and identify VEGFR as an upstream regulator of the Hippo pathway. We find that VEGFR activation by VEGF triggers PI3K/MAPK signaling, which subsequently inhibits LATS and activates the Hippo effectors YAP and TAZ. We further show that the Hippo pathway is a critical mediator of VEGF-induced angiogenesis and tumor vasculogenic mimicry. Thus, our work offers a biosensor tool for the study of the Hippo pathway and suggests a role for Hippo signaling in regulating blood vessel formation in physiological and pathological settings.

Tuberculosis knowledge, attitudes and practices of patients at primary health care facilities in a South African metropolitan: research towards improved health education.

BACKGROUND: Health education is important to empower patients and encourage their contribution towards tuberculosis (TB) control. In South Africa, health education activities are integrated into services provided at the primary health care (PHC) level. This study was conducted in a high TB burden metropolitan area in South Africa. The objective was to assess TB-related knowledge, attitudes and infection control practices of patients attending PHC facilities. METHODS: In September and October 2015, a cross-sectional survey using fieldworker-administered questionnaires was conducted among patients older than 17 years attending 40 PHC facilities in the Mangaung Metropolitan. Convenience sampling was used to select patients. Participation in the study was voluntary. Descriptive, inferential and multivariate logistic regression analyses were performed. Statistical significance was considered at alpha <0.05 and 95% confidence interval. RESULTS: A total of 507 patients' data were included in the analysis. Most of the patients knew that TB transmission is facilitated by crowded conditions (84.6%) and that pulmonary TB is contagious (73.0%). Surprisingly, the majority of patients also believed that one can get TB from sharing toothbrushes (85.0%) or kissing (65.0%). An overwhelming majority of patients perceived TB to be serious (89.7%), and concurred that taking treatment (97.2%) and opening windows to prevent transmission in PHC facilities (97.0%) are important. Being employed (AOR: 11.5; CI: 4.8-27.6), having received TB infection control information from a PHC facility (AOR: 2.2; CI: 1.5-3.4), and being a TB patient (AOR: 1.6; CI: 1.02-2.46) increased the likelihood of adopting good infection control practices. CONCLUSION: These findings highlight the need for health education efforts to strengthen accurate information dissemination to promote sound TB knowledge and attitudes among patients attending PHC facilities. Health education efforts should also capitalise on the positive finding of this study that information dissemination at PHC facilities increases good infection control practices.

5-Substituted 2-benzylidene-1-tetralone analogues as A1 and/or A2A antagonists for the potential treatment of neurological conditions.

Adenosine A1 and A2A receptors are attracting great interest as drug targets for their role in cognitive and motor deficits, respectively. Antagonism of both these adenosine receptors may offer therapeutic benefits in complex neurological diseases, such as Alzheimer's and Parkinson's disease. The aim of this study was to explore the affinity and selectivity of 2-benzylidene-1-tetralone derivatives as adenosine A1 and A2A receptor antagonists. Several 5-hydroxy substituted 2-benzylidene-1-tetralone analogues with substituents on ring B were synthesized and assessed as antagonists of the adenosine A1 and A2A receptors via radioligand binding assays. The results indicated that hydroxy substitution in the meta and para position of phenyl ring B, displayed the highest selectivity and affinity for the adenosine A1 receptor with Ki values in the low micromolar range. Replacement of ring B with a 2-amino-pyrimidine moiety led to compound 12 with an increase of affinity and selectivity for the adenosine A2A receptor. These substitution patterns led to enhanced adenosine A1 and A2A receptor binding affinity. The para-substituted 5-hydroxy analogue 3 behaved as an adenosine A1 receptor antagonists in a GTP shift assay performed with rat whole brain membranes expressing adenosine A1 receptors. In conclusion, compounds 3 and 12, showed the best adenosine A1 and A2A receptor affinity respectively, and therefore represent novel adenosine receptor antagonists that may have potential with further structural modifications as drug candidates for neurological disorders.

Unsuccessful TB treatment outcomes with a focus on HIV co-infected cases: a cross-sectional retrospective record review in a high-burdened province of South Africa.

BACKGROUND: South Africa did not meet the MDG targets to reduce TB prevalence and mortality by 50% by 2015, and the TB cure rate remains below the WHO target of 85%. TB incidence in the country is largely fuelled by the HIV epidemic, and co-infected patients are more likely to have unsuccessful TB treatment outcomes. This paper analyses the demographic and clinical characteristics of new TB patients with unsuccessful treatment outcomes, as well as factors associated with unsuccessful treatment outcomes for HIV co-infected patients. METHODS: A cross-sectional retrospective record review of routinely collected data for new TB cases registered in the Free State provincial electronic TB database between 2009 and 2012. The outcome variable, unsuccessful treatment, was defined as cases ≥15 years that 'died', 'failed' or 'defaulted' as the recorded treatment outcome. The data were subjected to descriptive and logistic regression analyses. RESULTS: From 2009 to 2012 there were 66,940 new TB cases among persons ≥15 years (with a recorded TB treatment outcome), of these 61% were co-infected with HIV. Unsuccessful TB treatment outcomes were recorded for 24.5% of co-infected cases and 15.3% of HIV-negative cases. In 2009, co-infected cases were 2.35 times more at risk for an unsuccessful TB treatment outcome (OR: 2.35; CI: 2.06-2.69); this figure decreased to 1.8 times by 2012 (OR: 1.80; CI: 1.63-1.99). Among the co-infected cases, main risk factors for unsuccessful treatment outcomes were: ≥ 65 years (AOR: 1.71; CI: 1.25-2.35); receiving treatment in healthcare facilities in District D (AOR: 1.15; CI 1.05-1.28); and taking CPT (and not ART) (AOR: 1.28; CI: 1.05-1.57). Females (AOR: 0.93; CI: 0.88-0.99) and cases with a CD4 count >350 (AOR: 0.40; CI: 0.36-0.44) were less likely to have an unsuccessful treatment outcome. CONCLUSIONS: The importance of TB-HIV/AIDS treatment integration is evident as co-infected patients on both ART and CPT, and those who have a higher CD4 count are less likely to have an unsuccessful TB treatment outcome. Furthermore, co-infected patients who require more programmatic attention are older people and males.

Predictors of uptake of human immunodeficiency virus testing by tuberculosis patients in Free State Province, South Africa.

SETTING: Two districts of the Free State Province in South Africa. OBJECTIVE: To determine the predictors of human immunodeficiency virus (HIV) test uptake by tuberculosis (TB) patients. DESIGN: A cross-sectional survey was conducted among 600 TB patients in 61 primary health care facilities. Probability proportional-to-size sampling was used to determine the number of patients recruited at each facility. Structured exit interviews were conducted with convenience samples of patients at these facilities. Descriptive and logistic regression analyses were performed on the data. RESULTS: The average age of the recruited TB patients was 38.4 years. The majority were female (n = 310, 51.7%), unmarried (n = 439, 73.3%), unemployed (n = 513, 85.5%) and had undertaken HIV testing (n = 405, 67.5%). In multivariate analysis, having received information on the relationship between TB and HIV (OR 5.4, 95%CI 3.1-9.5) was the strongest predictor of HIV test uptake among unmarried patients. Other associated factors included knowing/having lost someone ill with HIV/AIDS (acquired immune-deficiency syndrome; OR 3.6, 95%CI 2.2-5.8), female sex (OR 2.3, 95%CI 1.4-3.7), unemployment (OR 2.2, 95%CI 1.2-4.1) and undergoing retreatment for TB (OR 2.0, 95%CI 1.2-3.2). CONCLUSION: HIV test scale-up efforts should aim to increase TB patients' awareness of the relationship between TB and HIV/AIDS and consider the impact of socio-demographic factors.

The National Strategic Plan of South Africa: what are the prospects of success after the repeated failure of previous AIDS policy?

Hitherto, the story of HIV/AIDS in South Africa is, to a large extent, one of lost opportunities. Whereas the country has one of the worst epidemics in the world, consecutive national AIDS strategies have been repeatedly marked by failure over almost three decades. Understandably, South Africa's most recent HIV/AIDS policy, the HIV & AIDS and STI Strategic Plan for South Africa, 2007-2011 (NSP), has been greeted with general acclaim. However, what are its real prospects of success against the backdrop of the repeated failures of the past? The first objective of this review is to systematically identify the core reasons for past policy failures. Using a comprehensive analytical framework, this article presents a systematic review of the literature on postapartheid AIDS policy in South Africa. The analysis demonstrates that a complex interplay among the content, context, actors and process of AIDS policy created a gap between policy making and policy implementation, which rendered near-ideal AIDS policies ineffective. Secondly, we evaluate the chances of success of the current NSP by examining both the policy-making phase and the resulting policy document in light of the reasons for past policy failures. Our analysis shows that the NSP contains dynamic and comprehensive policy content, sensitive to the socio-economic and cultural dimensions of HIV/AIDS. However, many of the political actors that hampered treatment implementation in the past, and who deepened the gap between government and civil society, are still in office. Monetary and human resource shortages also create a policy context that is infertile for the implementation of a comprehensive HIV/AIDS strategy, as envisaged in the NSP. Finally, these health system restrictions have a clear negative impact on the process of policy implementation. Without the mobilization of people living with HIV/AIDS and their communities, the NSP will be ineffective in bridging the gap between policy intentions and policy implementation. The strength of this article lies in its systematic analysis of previous policy responses, as a basis for appraising current AIDS policy. Although such an approach tends to simplify the complexities of the actual policy environment, it nonetheless draws to the attention of policy participants the importance of and the complex interrelationships among the different dimensions of AIDS policy.

Slow to share: social capital and its role in public HIV disclosure among public sector ART patients in the Free State province of South Africa.

HIV serostatus disclosure to community members has been shown to have potential public and personal health benefits. This study examined the impact of bonding and bridging social capital (i.e. close and distant ties) on public disclosure and described the complex relationship between bonding and bridging social capital in the context of serostatus disclosure among AIDS patients enrolled in South Africa's public sector antiretroviral treatment (ART) program. Data were collected from a cohort of patients enrolled in the public sector ART program in the Free State province of South Africa. Semi-structured, face-to-face interviews were conducted with a random sample of 268 patients at three points in time (<6 months of ART, 6-12 months of ART, and 18-24 of months ART). The relationship between bonding and bridging social capital and the impact of different forms of social capital on public disclosure were determined using a fully cross-lagged regression model. The impact of bonding social capital (treatment and emotional buddy) on public disclosure was positive and invariant across time. The results from the cross-lagged regression indicated that bridging social capital (community health worker and support group) only encouraged public disclosure in the second year of treatment. At the start of treatment, bivariate analysis showed a strong negative association between bonding and bridging social capital, which diminished at follow-up and eventually disappeared in the second year of treatment. This study identified bonding social capital as a leverage to maximize potential benefits and minimize potential risks in order to shift the balance toward consistent public disclosure. Furthermore, the importance of bridging social capital initiatives is demonstrated, especially for the most vulnerable patients, those who cannot capitalize their bonding social capital by disclosing their HIV serostatus to family and friends at the start of treatment.

Rationing access to public-sector antiretroviral treatment during scale-up in South Africa: implications for equity.

As with other large-scale antiretroviral therapy (ART) programmes initiated in developing countries, rationing of ART in South Africa was inevitable in the face of limited human and infrastructural resources. This paper discusses rationing of ART and its implications for equity in South Africa, with a particular emphasis on the national programme in the Free State Province. We examine both the explicit and implicit dimensions of ART rationing, while considering the content of policy, programme design and implementation processes. The explicit rationing criteria included in the national comprehensive plan, as well as the associated treatment guidelines, direct and influence rationing decisions practised locally. However, implicit processes of rationing, which limit demand, are also wittingly and unwittingly introduced in several ways, and at all levels of the health service. Consequences of rationing manifest in the high numbers of patients lost to the system and the difficulties faced by the most impoverished clients in gaining access to ART services on an ongoing basis. Not losing sight of the equity element within rationing is important, and this aspect will have to be formally monitored for eventual success of the country's ART programme. ART roll-out processes also require ongoing efforts to build consensus and confidence in rationing, accomplished with a view to optimal fairness.

Short-term physical and emotional health outcomes of public sector ART in the Free State province of South Africa.

INTRODUCTION: In order to assess the health outcomes of the South African public sector antiretroviral treatment (ART) programme, it is important to gain a better understanding of the complex relationship between ART and the multidimensional construct quality of life (QoL). Because of the gap between supply and demand, equity issues arise concerning the provisioning of ART. OBJECTIVE: The aim of this paper is to examine how and to what extent public sector ART is related to the physical and emotional health of people living with HIV/AIDS (PLWHA). METHODS: The stratified random sample consisted of 371 AIDS patients on ART or medically certified for ART, but still awaiting treatment. A model of the relationships between patient characteristics (age and gender) and socio-economic position (educational level, income, type of dwelling, number of rooms), ART duration, and physical and emotional QoL was tested using structural equation modelling. RESULTS: Patients with a higher personal income (beta = .19, P < .05) and a larger dwelling (beta = .45, P < .01) were significantly more likely to enter the programme at this early stage. The model showed that the initial months of ART have been associated with significant improvements in the physical QoL (beta = .21, P < .01). Furthermore, patients on ART reported significantly higher levels of emotional well-being than patients awaiting treatment (beta = .10, P < .01). Finally, the results indicate that ART is not only directly associated with emotional QoL, but is also indirectly associated with emotional QoL via the mediating variable physical QoL (beta = .30, P < .01). CONCLUSIONS: The study suggests that the poorest of the poor are not the first beneficiaries of the public programme. Most importantly, the present findings demonstrate the positive physical and emotional health outcomes of the first 6 months of ART in the Free State, South Africa.

SANTA vs. public tuberculosis hospitals: the patient experience in the Free State, 2001/2002.

This paper reflects on the appropriateness of the decision to close down a non-governmental organisation (NGO), state-aided tuberculosis (TB) hospital in the Free State in 2003. Henceforth hospitalisation of TB patients would take place at public district hospitals. A survey conducted late-2001/early-2002 revealed a more positive patient experience of hospitalisation for TB in public hospitals than in the NGO hospital. Consideration of the patient experience serves to inform the debate concerning continued outsourcing of TB hospital care to NGOs in South Africa. This study discusses comparative findings in respect of patients' biographic and socio-economic characteristics, health beliefs, satisfaction with hospitalisation, experience of stigmatisation, adherence to treatment and absconding from hospital.

Assessment of the implementation of the primary health care package at selected sites in South Africa.

A major objective of public health policy in South Africa is to develop a district-based health service focused on the delivery of primary health care. The primary health care package has been developed to promote the delivery of a number of services at the primary level. This paper assesses the implementation of the package in eight historically disadvantaged urban renewal nodes singled out for accelerated development through the government's urban renewal strategy. Data were gathered by way of interviews with primary health care facility managers and programme co-ordinators and through physical observations at facilities. The findings show that while some facilities were able to offer clients most of the services specified by the package, many others were unable do so. The urban renewal nodes differed noticeably in this respect.

Social research as an intervention tool in tuberculosis control.

Our multidisciplinary project on TB control in the Free State, South Africa, is targeting two dimensions for intervention: firstly, patients, to facilitate compliance and improve quality of care; secondly, the health care system, to identify weaknesses that require remedying and best practices to promote better TB control. This communication illustrates how social scientists can contribute towards the implementation of interventions related to their research, thus influencing TB policy, programme planning and practice more directly.

Studies of genetically defined chimeras of a European type A virus and a South African Territories type 2 virus reveal growth determinants for foot-and-mouth disease virus.

The three South African Territories (SAT) types of foot-and-mouth disease virus (FMDV) display great genetic and antigenic diversity, resulting from the independent evolution of these viruses in different geographical localities. For effective control of the disease in such areas, the use of custom-made vaccines is required. To circumvent the tedious process of vaccine strain selection, an alternative in the control process is being investigated. Specifically, it is proposed to replace the antigenic determinants of an infectious genome-length cDNA copy of a good SAT vaccine strain with those of appropriate field strains, producing custom-made FMDV chimeras for use in vaccine production. Here the construction of an infectious genome-length cDNA copy of the SAT2 vaccine strain, ZIM/7/83, is described, created utilizing an exchange-cassette strategy with an existing A(12) genome-length cDNA clone. The virus derived from this cDNA (designated vSAT2) displayed excellent growth properties in cell culture, indicating its potential usefulness in the production of custom-made vaccine strains. Evaluation of the growth of various SAT2/A12 chimeras created during the derivation of SAT2 infectious cDNA suggested incompatibilities between the non-structural proteins of ZIM/7/83 and the 5' UTR of A(12).

Ablation of post-surgical intra-atrial reentrant tachycardia. Predilection target sites and mapping approach.

BACKGROUND: Atrial arrhythmias are a frequent complication of atrial surgery. The location of these tachycardias is very diverse due to the individual difference in the original anatomy, surgical corrections, and effects of atrial fibrosis. Nevertheless some recurrent patterns are emerging. METHODS AND RESULTS: Forty-five patients underwent 51 ablation procedures between September 1995 and March 2001 using conventional mapping and temperature-controlled ablation. A duadecapolar catheter was swept from anterior to posterior in the right (and/or left) atrium, allowing for rapid mapping followed by entrainment confirmation. Twenty-eight patients had corrected congenital heart disease, 17 surgery for acquired heart disease. One hundred and sixteen arrhythmias were found, 86 circuits were targeted, 81 with success (94%). Despite the heterogeneous anatomy, the same targets were often encountered: the posterior isthmus between the inferior vena cava and the tricuspid ring (62%), the gap between the inferior vena cava and the atriotomy scar (49%), and the region around the atriopulmonary connection in Fontans (two out of four patients). After a mean follow-up of 24 months, 13 patients had a recurrent arrhythmia (29%) after their last procedure. There was a significant association between the number of circuits found during the initial procedure and the likelihood of recurrent arrhythmias. CONCLUSION: Knowledge of anatomical predilection sites and mapping the right (and/or left) atrium with a 'sweeping Halo technique' allow for effective ablation of most post-surgical atrial tachycardias. Severely damaged atria with multiple arrhythmias may require 'preventive' ablation of all recognizable channels.

The 3A non-structural-protein coding region of the southern African SAT type isolates differs from that of other foot-and-mouth disease viruses.

The 3A non-structural protein of foot-and-mouth disease viruses is a relatively conserved protein comprising 153 amino acids. Recent studies have demonstrated correlation between mutations in the 3A non-structural-protein-coding region, including a 10-amino acid deletion, and attenuation of the viruses in cattle. Although the 3A coding region of several type A, O and C isolates has previously been described, nucleotide sequence data of the 3A coding region of the South African Types (SAT) 1, 2 and 3 viruses are limited. Therefore, the 3A non-structural-coding region of different SAT serotypes was determined, analysed and compared to that of European, South American and Asian isolates. The 3A regions of the SAT isolates investigated differed markedly from that of types A, O, C and Asia-1, but were similar within the group.

Right atrial angiographic evaluation of the posterior isthmus: relevance for ablation of typical atrial flutter.

BACKGROUND: Gaining anatomic information about the posterior isthmus is not generally part of flutter ablation procedures. We postulated that right atrial (RA) angiography could rationalize the ablation approach by revealing the conformation of the isthmus. METHODS AND RESULTS: In 100 consecutive patients, biplane RA angiography was performed before ablation to guide catheter contact with the isthmus along its length. Angiography showed a wide variation in the width of the isthmus (17 to 54 mm; 31.3+/-7.9), its angle with the inferior vena cava in the right anterior oblique projection (68 degrees to 114 degrees; 90.3+/-9.0 degrees ), and its lateral position relative to the inferior vena cava in the left anterior oblique projection. A deep sub-Eustachian recess was revealed in 47%, with a mean depth of 4.3+/-2.1 mm (1.5 to 9.4). A Eustachian valve was visualized in 24%. Ablation resulted in bidirectional conduction block (which could be transient) in all, with a median of 2 dragging radiofrequency (RF) applications (2.3+/-2.5 RF applications; 57 degrees C, < or =99 seconds each). Permanent block was achieved in 99%, with a median of 3 RF applications (3.4+/-3.0). The presence of a Eustachian valve or concave isthmus was associated with statistically more RF applications; the same trend was seen for patients with deep pouches. The number of RF applications decreased statistically throughout the study, indicating a learning curve. No patient had a recurrence after a follow-up of 13+/-11 months. CONCLUSIONS: Right atrial angiography reveals a highly variable isthmus anatomy, often showing particular configurations that can make ablation more laborious. Rational adaptation of the ablation approach to these anatomic findings may contribute to successful ablation.

The implementation of the Choice on Termination of Pregnancy Act: some empirical findings.

The Choice on Termination of Pregnancy Act of 1996 substantially liberalised abortion law. Whilst a substantial number of terminations of pregnancies (TOPs) have already been performed in terms of the new Act, it has also surfaced that an array of factors of various kinds may impede its further implementation and operation. A study was undertaken to determine the nature and extent of any such impediments to the implementation of the Choice on Termination of Pregnancy Act. More specifically a survey was conducted amongst a sample of 75 women who had undergone a TOP since the implementation of the Act; health professionals and social workers who provide TOP services (n = 16); and health professionals and social workers who are in a position to refer women to TOP facilities (n = 63). Overall, the clients were well treated at the TOP facilities, and were satisfied with the service given to them. However, post-counselling and to a lesser extent pre-counselling, is lacking. Counselling is important as a considerable proportion of the clients suffered from emotional feelings usually associated with depression and/or self-reproach before and after the termination procedure. Furthermore these clients did not usually discuss their termination with family members. TOP service providers were dissatisfied with the TOP facilities, especially the insufficient number of consultation and counselling rooms. Health care workers in a position to refer clients to TOP facilities were not always willing to do so, thereby obstructing the referral system. In the main, it is recommended that the entire TOP procedure should be done at clinics/hospitals so that clients will not have to do inductions at home, more trained staff should be available, facilities should be adequate and accessible, and there should be psychological support for staff.

Characterization of the structural-protein-coding region of SAT 2 type foot-and-mouth disease virus.

The South African Territories (SAT) types of foot-and-mouth disease (FMD) virus show marked genomic and antigenic variation in sub-Saharan Africa that is to a large extent geographically determined. This has implications for selection of appropriate vaccine strains as well as the accuracy of laboratory diagnosis. However, adaptation of field isolates as vaccine strains is cumbersome, time consuming and expensive. We propose the construction of recombinant viruses in which specific antigenic determinants can be manipulated. To achieve this goal, the structural-protein-coding region of a SAT 2 vaccine strain, ZIM 7/83/2, was determined and compared with two other known SAT 2 P1 regions. Five hypervariable regions were identified of which four are situated within VP1. The cleavage sites for proteolytic processing differs from serotype A, while the junction between P1/2A is variable within the SAT 2 serotype. These differences could influence the construction of recombinant vaccines.